Nanoliposomes as nonviral vectors in cancer gene therapy

Abstract

Nonviral vectors, such as liposomes, offer potential for targeted gene delivery in cancer therapy. Liposomes, composed of phospholipid vesicles, have demonstrated efficacy as nanocarriers for genetic tools, addressing the limitations of off-targeting and degradation commonly associated with traditional gene therapy approaches. Due to their biocompatibility, stability, and tunable physicochemical properties, they offer potential in overcoming the challenges associated with gene therapy, such as low transfection efficiency and poor stability in biological fluids. Despite these advancements, there remains a gap in understanding the optimal utilization of nanoliposomes for enhanced gene delivery in cancer treatment. This review delves into the present state of nanoliposomes as carriers for genetic tools in cancer therapy, sheds light on their potential to safeguard genetic payloads and facilitate cell internalization alongside the evolution of smart nanocarriers for targeted delivery. The challenges linked to their biocompatibility and the factors that restrict their effectiveness in gene delivery are also discussed along with exploring the potential of nanoliposomes in cancer gene therapy strategies by analyzing recent advancements and offering future directions.

Keywords

CRISPR/Cas9 / liposome / nonviral vector / shRNA / siRNA

References

1	T Wirth, N Parker, S Yl?-Herttuala. History of gene therapy. Gene. 2013;525(2):162-169.
2	M Ashrafizadeh, A Zarrabi, A Bigham, et al. (Nano)platforms in breast cancer therapy: drug/gene delivery, advanced nanocarriers and immunotherapy. Med Res Rev. 2023;43(6):2115-2176.
3	K Karimi, S Mojtabavi, PM Tehrany, et al. Chitosan-based nanoscale delivery systems in hepatocellular carcinoma: versatile bio-platform with theranostic application. Int J Biol Macromol. 2023;242:124935.
4	K Yaray, A Norbakhsh, H Rashidzadeh, et al. Chemoradiation therapy of 4T1 cancer cells with methotrexate conjugated platinum nanoparticles under X-Ray irradiation. Inorg Chem Commun. 2023;150:110457.
5	A Taheriazam, GGY Abad, S Hajimazdarany, et al. Graphene oxide nanoarchitectures in cancer biology: nano-modulators of autophagy and apoptosis. J Control Release. 2023;354:503-522.
6	M Cavazzana-Calvo, A Thrasher, F Mavilio. The future of gene therapy. Nature. 2004;427(6977):779-781.
7	M Hashemi, S Hajimazdarany, CD Mohan, et al. Long non-coding RNA/epithelial-mesenchymal transition axis in human cancers: tumorigenesis, chemoresistance, and radioresistance. Pharmacol Res. 2022;186:106535.
8	YQ Almajidi, MM Kadhim, F Alsaikhan, et al. Doxorubicin-loaded micelles in tumor cell-specific chemotherapy. Environ Res. 2023;227:115722.
9	S Mirzaei, MH Gholami, F Hashemi, et al. Employing siRNA tool and its delivery platforms in suppressing cisplatin resistance: approaching to a new era of cancer chemotherapy. Life Sci. 2021;277:119430.
10	M Delfi, R Sartorius, M Ashrafizadeh, et al. Self-assembled peptide and protein nanostructures for anti-cancer therapy: targeted delivery, stimuli-responsive devices and immunotherapy. Nano Today. 2021;38:101119.
11	S Mirzaei, A Zarrabi, F Hashemi, et al. Regulation of Nuclear Factor-KappaB (NF-κB) signaling pathway by non-coding RNAs in cancer: inhibiting or promoting carcinogenesis? Cancer Lett. 2021;509:63-80.
12	W Zhang, A Mehta, Z Tong, L Esser, NH Voelcker. Development of polymeric nanoparticles for blood–brain barrier transfer—strategies and challenges. Adv Sci. 2021;8:2003937.
13	M Ashrafizadeh, A Zarrabi, K Hushmandi, et al. Progress in natural compounds/siRNA co-delivery employing nanovehicles for cancer therapy. ACS Comb Sci. 2020;22(12):669-700.
14	M Ashrafizadeh, K Hushmandi, E Rahmani Moghadam, et al. Progress in delivery of siRNA-based therapeutics employing nano-vehicles for treatment of prostate cancer. Bioeng. 2020;7(3):91.
15	R Mohammadinejad, A Dehshahri, V Sagar Madamsetty, et al. In vivo gene delivery mediated by non-viral vectors for cancer therapy. J Control Release. 2020;325:249-275.
16	M Ashrafizadeh, A Zarrabi, H Karimi-Maleh, et al. (Nano) platforms in bladder cancer therapy: challenges and opportunities. Bioeng Transl Med. 2023;8(1):e10353.
17	Y Yu, Y Gao, L He, et al. Biomaterial-based gene therapy. MedComm. 2023;4(3):e259.
18	TM Allen, PR Cullis. Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev. 2013;65(1):36-48.
19	A Accardo, S Mannucci, E Nicolato, et al. Easy formulation of liposomal doxorubicin modified with a bombesin peptide analogue for selective targeting of GRP receptors overexpressed by cancer cells. Drug Deliv Transl Res. 2019;9(1):215-226.
20	MR Aronson, SH Medina, MJ Mitchell. Peptide functionalized liposomes for receptor targeted cancer therapy. APL Bioeng. 2021;5(1):011501.
21	W Chen, EM Goldys, W Deng. Light-induced liposomes for cancer therapeutics. Prog Lipid Res. 2020;79:101052.
22	A Watts. Membrane structure and dynamics. Curr Opin Cell Biol. 1989;1(4):691-700.
23	L Coderch, J Fonollosa, M De Pera, J Estelrich, A De La Maza, J Parra. Influence of cholesterol on liposome fluidity by EPR: relationship with percutaneous absorption. J Control Release. 2000;68(1):85-95.
24	AA Khan, KS Allemailem, SA Almatroodi, A Almatroudi, AH Rahmani. Recent strategies towards the surface modification of liposomes: an innovative approach for different clinical applications. 3 Biotech. 2020;10(4):1-15.
25	JH Sakamoto, AL van de Ven, B Godin, et al. Enabling individualized therapy through nanotechnology. Pharmacol Res. 2010;62(2):57-89.
26	A Samad, Y Sultana, M Aqil. Liposomal drug delivery systems: an update review. Curr Drug Deliv. 2007;4(4):297-305.
27	Y Malam, M Loizidou, AM Seifalian. Liposomes and nanoparticles: nanosized vehicles for drug delivery in cancer. Trends Pharmacol Sci. 2009;30(11):592-599.
28	E Rideau, R Dimova, P Schwille, FR Wurm, K Landfester. Liposomes and polymersomes: a comparative review towards cell mimicking. Chem Soc Rev. 2018;47(23):8572-8610.
29	F Szoka Jr, D Papahadjopoulos. Comparative properties and methods of preparation of lipid vesicles (liposomes). Annu Rev Biophys Bioeng. 1980;9(1):467-508.
30	PV Pawar, SV Gohil, JP Jain, N Kumar. Functionalized polymersomes for biomedical applications. Polym Chem. 2013;4(11):3160-3176.
31	P Walde, K Cosentino, H Engel, P Stano. Giant vesicles: preparations and applications. ChemBioChem. 2010;11(7):848-865.
32	A Villalba, S Rodriguez-Fernandez, RM Ampudia, et al. Preclinical evaluation of antigen-specific nanotherapy based on phosphatidylserine-liposomes for type 1 diabetes. Artif Cells Nanomed Biotechnol. 2020;48(1):77-83.
33	L Xue, D Wang, X Zhang, S Xu, N Zhang. Targeted and triple therapy-based liposomes for enhanced treatment of rheumatoid arthritis. Int J Pharm. 2020;586:119642.
34	J Li, F Ding, X Qian, et al. Anti-inflammatory cytokine IL10 loaded cRGD liposomes for the targeted treatment of atherosclerosis. J Microencapsulation. 2020:1-19.
35	L Kong, XT Li, YN Ni, et al. Transferrin-modified osthole PEGylated liposomes travel the blood-brain barrier and mitigate Alzheimer's disease-related pathology in APP/PS-1 mice. Int J Nanomed. 2020;15:2841-2858.
36	D Kashyap, HS Tuli, MB Yerer, et al. Natural product-based nanoformulations for cancer therapy: opportunities and challenges. Semin Cancer Biol. 2021;69:5-23.
37	MK Shanmugam, S Warrier, AP Kumar, G Sethi, F Arfuso. Potential role of natural compounds as anti-angiogenic agents in cancer. Curr Vasc Pharmacol. 2017;15(6):503-519.
38	ME Cano, D Lesur, V Bincoletto, et al. Synthesis of defined oligohyaluronates-decorated liposomes and interaction with lung cancer cells. Carbohydr Polym. 2020;248:116798.
39	B Tang, Y Peng, Q Yue, et al. Design, preparation and evaluation of different branched biotin modified liposomes for targeting breast cancer. Eur J Med Chem. 2020;193:112204.
40	VP Torchilin. Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov. 2005;4(2):145-160.
41	C Li, Y Deng. A novel method for the preparation of liposomes: freeze drying of monophase solutions. J Pharm Sci. 2004;93(6):1403-1414.
42	J Juan-Colás, L Dresser, K Morris, et al. The mechanism of vesicle solubilization by the detergent sodium dodecyl sulfate. Langmuir. 2020;36(39):11499-11507.
43	A Gouda, OS Sakr, M Nasr, O Sammour. Ethanol injection technique for liposomes formulation: an insight into development, influencing factors, challenges and applications. J Drug Deliv Sci Technol. 2021;61:102174.
44	N-Q Shi, X-R Qi. Preparation of drug liposomes by reverse-phase evaporation. Liposome-Based Drug Deliv Syst. 2021:37-46.
45	G Wang, Y Yang, D Yi, et al. Eudragit S100 prepared pH-responsive liposomes-loaded betulinic acid against colorectal cancer in vitro and in vivo. J Liposome Res. 2022;32(3):250-264.
46	D Carugo, E Bottaro, J Owen, E Stride, C Nastruzzi. Liposome production by microfluidics: potential and limiting factors. Sci Rep. 2016;6(1):25876.
47	C Jaafar-Maalej, C Charcosset, H Fessi. A new method for liposome preparation using a membrane contactor. J Liposome Res. 2011;21(3):213-220.
48	L Sercombe, T Veerati, F Moheimani, SY Wu, AK Sood, S Hua. Advances and challenges of liposome assisted drug delivery. Front Pharmacol. 2015;6:286.
49	YS Tarahovsky, R Koynova, RC MacDonald. DNA release from lipoplexes by anionic lipids: correlation with lipid mesomorphism, interfacial curvature, and membrane fusion. Biophys J. 2004;87(2):1054-1064.
50	Y Wang, R Zhang, L Tang, L Yang. Nonviral delivery systems of mRNA vaccines for cancer gene therapy. Pharmaceutics. 2022;14(3):512.
51	R Zhang, L Tang, Y Tian, et al. DP7-C-modified liposomes enhance immune responses and the antitumor effect of a neoantigen-based mRNA vaccine. J Control Release. 2020;328:210-221.
52	A Nosova, O Koloskova, A Nikonova, et al. Diversity of PEGylation methods of liposomes and their influence on RNA delivery. MedChemComm. 2019;10(3):369-377.
53	W-Y Yu, N Zhang. Surface modification of nanocarriers for cancer therapy. Curr Nanosci. 2009;5(2):123-134.
54	D Peer, JM Karp, S Hong, OC Farokhzad, R Margalit, R Langer. Nanocarriers as an emerging platform for cancer therapy. Nano-Enabled Med Appl. 2020:61-91.
55	SK Das. Drug delivery: principles and applications. Am J Pharm Educ. 2006;70(4):94.
56	J Zhou, J Rossi. Aptamers as targeted therapeutics: current potential and challenges. Nat Rev Drug Discov. 2017;16(3):181-202.
57	MA Subhan, SA Attia, VP Torchilin. Advances in siRNA delivery strategies for the treatment of MDR cancer. Life Sci. 2021;274:119337.
58	TC Roberts, K Ezzat, SE Andaloussi, MS Weinberg. Synthetic SiRNA delivery: progress and prospects. SiRNA Deliv Methods. 2016;1364:291-310.
59	S Supe, A Upadhya, K Singh. Role of small interfering RNA (siRNA) in targeting ocular neovascularization: a review. Exp Eye Res. 2020;202:108329.
60	MR Lares, JJ Rossi, DL Ouellet. RNAi and small interfering RNAs in human disease therapeutic applications. Trends Biotechnol. 2010;28(11):570-579.
61	S Najafi, SC Tan, P Raee, et al. Gene regulation by antisense transcription: a focus on neurological and cancer diseases. Biomed Pharmacother. 2022;145:112265.
62	MA Subhan, V Torchilin. siRNA based drug design, quality, delivery and clinical translation. Nanomed Nanotechnol Biol Med. 2020;29:102239.
63	MDA Paskeh, A Mehrabi, MH Gholami, et al. EZH2 as a new therapeutic target in brain tumors: molecular landscape, therapeutic targeting and future prospects. Biomed Pharmacother. 2022;146:112532.
64	A Alshehri, A Grabowska, S Stolnik. Pathways of cellular internalisation of liposomes delivered siRNA and effects on siRNA engagement with target mRNA and silencing in cancer cells. Sci Rep. 2018;8(1):3748.
65	CY Loh, A Arya, AF Naema, WF Wong, G Sethi, CY Looi. Signal transducer and activator of transcription (STATs) proteins in cancer and inflammation: functions and therapeutic implication. Front Oncol. 2019;9:48.
66	JH Lee, C Kim, G Sethi, KS Ahn. Brassinin inhibits STAT3 signaling pathway through modulation of PIAS-3 and SOCS-3 expression and sensitizes human lung cancer xenograft in nude mice to paclitaxel. Oncotarget. 2015;6(8):6386-6405.
67	C Kim, SK Cho, S Kapoor, et al. β-Caryophyllene oxide inhibits constitutive and inducible STAT3 signaling pathway through induction of the SHP-1 protein tyrosine phosphatase. Mol Carcinog. 2014;53(10):793-806.
68	YY Jung, IJ Ha, J-Y Um, G Sethi, KS Ahn. Fangchinoline diminishes STAT3 activation by stimulating oxidative stress and targeting SHP-1 protein in multiple myeloma model. J Adv Res. 2021;35:245-257.
69	JH Lee, CD Mohan, A Deivasigamani, et al. Brusatol suppresses STAT3-driven metastasis by downregulating epithelial-mesenchymal transition in hepatocellular carcinoma. J Adv Res. 2020;26:83-94.
70	YY Jung, JH Ko, JY Um, et al. LDL cholesterol promotes the proliferation of prostate and pancreatic cancer cells by activating the STAT3 pathway. J Cell Physiol. 2020;236(7):5253-5264.
71	M Garg, MK Shanmugam, V Bhardwaj, et al. The pleiotropic role of transcription factor STAT3 in oncogenesis and its targeting through natural products for cancer prevention and therapy. Med Res Rev. 2020.
72	A Jose, S Labala, VV Venuganti. Co-delivery of curcumin and STAT3 siRNA using deformable cationic liposomes to treat skin cancer. J Drug Target. 2017;25(4):330-341.
73	A Jose, S Labala, KM Ninave, SK Gade, VVK Venuganti. Effective skin cancer treatment by topical co-delivery of curcumin and STAT3 siRNA using cationic liposomes. AAPS Pharm Sci Technol. 2018;19(1):166-175.
74	ST Hwang, C Kim, JH Lee, et al. Cycloastragenol can negate constitutive STAT3 activation and promote paclitaxel-induced apoptosis in human gastric cancer cells. Phytomedicine. 2019;59:152907.
75	MK Mahabady, S Mirzaei, H Saebfar, et al. Noncoding RNAs and their therapeutics in paclitaxel chemotherapy: mechanisms of initiation, progression, and drug sensitivity. J Cell Physiol. 2022;237(5):2309-2344.
76	M Ashrafizadeh, A Zarrabi, K Hushmandi, et al. Lung cancer cells and their sensitivity/resistance to cisplatin chemotherapy: role of microRNAs and upstream mediators. Cell Signal. 2020;78:109871.
77	W Wei, PP Lv, XM Chen, et al. Codelivery of mTERT siRNA and paclitaxel by chitosan-based nanoparticles promoted synergistic tumor suppression. Biomaterials. 2013;34(15):3912-3923.
78	X Sun, Y Chen, H Zhao, et al. Dual-modified cationic liposomes loaded with paclitaxel and survivin siRNA for targeted imaging and therapy of cancer stem cells in brain glioma. Drug Deliv. 2018;25(1):1718-1727.
79	Y Yang, Y Yang, J Yang, X Zhao, X Wei. Tumor microenvironment in ovarian cancer: function and therapeutic strategy. Front Cell Dev Biol. 2020;8:758.
80	X Sun, X Lv, Y Yan, et al. Hypoxia-mediated cancer stem cell resistance and targeted therapy. Biomed Pharmacother. 2020;130:110623.
81	K Saxena, MK Jolly, K Balamurugan. Hypoxia, partial EMT and collective migration: emerging culprits in metastasis. Transl Oncol. 2020;13(11):100845.
82	J Guan, J Sun, F Sun, et al. Hypoxia-induced tumor cell resistance is overcome by synergistic GAPDH-siRNA and chemotherapy co-delivered by long-circulating and cationic-interior liposomes. Nanoscale. 2017;9(26):9190-9201.
83	Y Kong, Y Li, Y Luo, et al. circNFIB1 inhibits lymphangiogenesis and lymphatic metastasis via the miR-486-5p/PIK3R1/VEGF-C axis in pancreatic cancer. Mol Cancer. 2020;19(1):82.
84	M Xie, T Yu, X Jing, et al. Exosomal circSHKBP1 promotes gastric cancer progression via regulating the miR-582-3p/HUR/VEGF axis and suppressing HSP90 degradation. Mol Cancer. 2020;19(1):112.
85	LY Jia, MK Shanmugam, G Sethi, A Bishayee. Potential role of targeted therapies in the treatment of triple-negative breast cancer. Anticancer Drugs. 2016;27(3):147-155.
86	ZZ Yang, JQ Li, ZZ Wang, DW Dong, XR Qi. Tumor-targeting dual peptides-modified cationic liposomes for delivery of siRNA and docetaxel to gliomas. Biomaterials. 2014;35(19):5226-5239.
87	Z Lu, T Pang, X Yin, et al. Delivery of TSPAN1 siRNA by novel Th17 targeted cationic liposomes for gastric cancer intervention. J Pharm Sci. 2020;109(9):2854-2860.
88	J Chen, Z Yu, H Chen, J Gao, W Liang. Transfection efficiency and intracellular fate of polycation liposomes combined with protamine. Biomaterials. 2011;32(5):1412-1418.
89	Y Takakura, M Nishikawa, F Yamashita, M Hashida. Influence of physicochemical properties on pharmacokinetics of non-viral vectors for gene delivery. J Drug Target. 2002;10(2):99-104.
90	J Lee, HJ Ahn. PEGylated DC-Chol/DOPE cationic liposomes containing KSP siRNA as a systemic siRNA delivery Carrier for ovarian cancer therapy. Biochem Biophys Res Commun. 2018;503(3):1716-1722.
91	RM Levine, CV Dinh, MA Harris, E Kokkoli. Targeting HPV-infected cervical cancer cells with PEGylated liposomes encapsulating siRNA and the role of siRNA complexation with polyethylenimine. Bioeng Transl Med. 2016;1(2):168-180.
92	JJ Verhoef, TJ Anchordoquy. Questioning the use of PEGylation for drug delivery. Drug Deliv Transl Res. 2013;3(6):499-503.
93	T Ishida, X Wang, T Shimizu, K Nawata, H Kiwada. PEGylated liposomes elicit an anti-PEG IgM response in a T cell-independent manner. J Control Release. 2007;122(3):349-355.
94	AS Abu Lila, H Kiwada, T Ishida. The accelerated blood clearance (ABC) phenomenon: clinical challenge and approaches to manage. J Control Release. 2013;172(1):38-47.
95	Y Mima, Y Hashimoto, T Shimizu, H Kiwada, T Ishida. Anti-PEG IgM is a major contributor to the accelerated blood clearance of polyethylene glycol-conjugated protein. Mol Pharm. 2015;12(7):2429-2435.
96	Q Yang, SK Lai. Anti-PEG immunity: emergence, characteristics, and unaddressed questions. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2015;7(5):655-677.
97	WT Godbey, KK Wu, GJ Hirasaki, AG Mikos. Improved packing of poly(ethylenimine)/DNA complexes increases transfection efficiency. Gene Ther. 1999;6(8):1380-1388.
98	ND Sonawane, FC Szoka, AS Verkman. Chloride accumulation and swelling in endosomes enhances DNA transfer by polyamine-DNA polyplexes. J Biol Chem. 2003;278(45):44826-44831.
99	S H?bel, A Aigner. Polyethylenimines for siRNA and miRNA delivery in vivo. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2013;5(5):484-501.
100	T Li, M Ashrafizadeh, Y Shang, Y Nuri Ertas, G Orive. Chitosan-functionalized bioplatforms and hydrogels in breast cancer: immunotherapy, phototherapy and clinical perspectives. Drug Discov Today. 2024;29(1):103851.
101	H Nosrati, M Salehiabar, J Charmi, et al. Enhanced in vivo radiotherapy of breast cancer using gadolinium oxide and gold hybrid nanoparticles. ACS Appl Bio Mater. 2023;6(2):784-792.
102	H Rashidzadeh, F Seidi, M Ghaffarlou, et al. Preparation of alginate coated Pt nanoparticle for radiosensitization of breast cancer tumor. Int J Biol Macromol. 2023;233:123273.
103	M Salehiabar, M Ghaffarlou, A Mohammadi, et al. Targeted CuFe2O4 hybrid nanoradiosensitizers for synchronous chemoradiotherapy. J Control Release. 2023;353:850-863.
104	YN Ertas, K Abedi Dorcheh, A Akbari, E Jabbari. Nanoparticles for targeted drug delivery to cancer stem cells: a review of recent advances. Nanomaterials. 2021;11(7):1755.
105	K Yaray, H Rashidzadeh, F Mozafari, et al. CuFe2O4 decorated with BSA as a potential nanoradioenhancer for enhanced X-ray radiation therapy of brain tumor. Chem Pap. 2023:1-10.
106	B Colak, YN Ertas. Implantable, 3D-printed alginate scaffolds with bismuth sulfide nanoparticles for the treatment of local breast cancer via enhanced radiotherapy. ACS Appl Mater Interfaces. 2024;16(13):15718-15729.
107	L Zhou, R Cheng, H Tao, et al. Endosomal pH-activatable poly(ethylene oxide)-graft-doxorubicin prodrugs: synthesis, drug release, and biodistribution in tumor-bearing mice. Biomacromolecules. 2011;12(5):1460-1467.
108	M Sako, F Song, A Okamoto, et al. Key determinants of siRNA delivery mediated by unique pH-responsive lipid-based liposomes. Int J Pharm. 2019;569:118606.
109	Y Yao, T Wang, Y Liu, N Zhang. Co-delivery of sorafenib and VEGF-siRNA via pH-sensitive liposomes for the synergistic treatment of hepatocellular carcinoma. Artif Cells Nanomed Biotechnol. 2019;47(1):1374-1383.
110	X Zang, H Ding, X Zhao, et al. Anti-EphA10 antibody-conjugated pH-sensitive liposomes for specific intracellular delivery of siRNA. Int J Nanomed. 2016;11:3951-3967.
111	R Nahire, R Hossain, R Patel, et al. pH-triggered echogenicity and contents release from liposomes. Mol Pharm. 2014;11(11):4059-4068.
112	DT Auguste, K Furman, A Wong, et al. Triggered release of siRNA from poly(ethylene glycol)-protected, pH-dependent liposomes. J Control Release. 2008;130(3):266-274.
113	G Wu, Y-Z Fang, S Yang, JR Lupton, ND Turner. Glutathione metabolism and its implications for health. J Nutr. 2004;134(3):489-492.
114	C Kim, SG Lee, WM Yang, et al. Formononetin-induced oxidative stress abrogates the activation of STAT3/5 signaling axis and suppresses the tumor growth in multiple myeloma preclinical model. Cancer Lett. 2018;431:123-141.
115	X Guo, Y Cheng, X Zhao, Y Luo, J Chen, WE Yuan. Advances in redox-responsive drug delivery systems of tumor microenvironment. J Nanobiotechnology. 2018;16(1):1-10.
116	J Zhang, KS Ahn, C Kim, et al. Nimbolide-induced oxidative stress abrogates STAT3 signaling cascade and inhibits tumor growth in transgenic adenocarcinoma of mouse prostate model. Antioxid Redox Signal. 2016;24(11):575-589.
117	A Kirtonia, G Sethi, M Garg. The multifaceted role of reactive oxygen species in tumorigenesis. Cell Mol Life Sci. 2020;77(22):4459-4483.
118	P Kumar, B Liu, G Behl. A comprehensive outlook of synthetic strategies and applications of redox-responsive nanogels in drug delivery. Macromol Biosci. 2019;19(8):1900071.
119	X Chen, Y Zhang, C Tang, et al. Co-delivery of paclitaxel and anti-survivin siRNA via redox-sensitive oligopeptide liposomes for the synergistic treatment of breast cancer and metastasis. Int J Pharm. 2017;529(1-2):102-115.
120	W Zhao, Y Zhao, Q Wang, T Liu, J Sun, R Zhang. Remote light-responsive nanocarriers for controlled drug delivery: advances and perspectives. Small. 2019;15(45):1903060.
121	B Colak, MC Cihan, YN Ertas. 3D-Printed, Implantable Alginate/CuS nanoparticle scaffolds for local tumor treatment via synergistic photothermal, photodynamic, and chemodynamic therapy. Acs Appl Nano Mater. 2023;6:16076-16085.
122	YN Ertas, D Ertas, A Erdem, F Segujja, S Dulchavsky, N Ashammakhi. Diagnostic, therapeutic, and theranostic multifunctional microneedles. Small. 2024:e2308479.
123	J Olejniczak, C-J Carling, A Almutairi. Photocontrolled release using one-photon absorption of visible or NIR light. J Control Release. 2015;219:18-30.
124	F Ding, X Gao, X Huang, et al. Polydopamine-coated nucleic acid nanogel for siRNA-mediated low-temperature photothermal therapy. Biomaterials. 2020;245:119976.
125	X Xie, Y Yang, Y Yang, X Mei. Photolabile-caged peptide-conjugated liposomes for siRNA delivery. J Drug Target. 2015;23(9):789-799.
126	Y Yang, Y Yang, X Xie, et al. Dual-modified liposomes with a two-photon-sensitive cell penetrating peptide and NGR ligand for siRNA targeting delivery. Biomaterials. 2015;48:84-96.
127	X Liu, AB Madhankumar, B Slagle-Webb, JM Sheehan, N Surguladze, JR Connor. Heavy chain ferritin siRNA delivered by cationic liposomes increases sensitivity of cancer cells to chemotherapeutic agents. Cancer Res. 2011;71(6):2240-2249.
128	T Yin, P Wang, J Li, et al. Ultrasound-sensitive siRNA-loaded nanobubbles formed by hetero-assembly of polymeric micelles and liposomes and their therapeutic effect in gliomas. Biomaterials. 2013;34(18):4532-4543.
129	D Bhavsar, K Subramanian, S Sethuraman, UM Krishnan. ‘Nano-in-nano’ hybrid liposomes increase target specificity and gene silencing efficiency in breast cancer induced SCID mice. Eur J Pharm Biopharm. 2017;119:96-106.
130	S Taetz, A Bochot, C Surace, et al. Hyaluronic acid-modified DOTAP/DOPE liposomes for the targeted delivery of anti-telomerase siRNA to CD44-expressing lung cancer cells. Oligonucleotides. 2009;19(2):103-116.
131	N Golkar, SM Samani, AM Tamaddon. Data on cell growth inhibition induced by anti-VEGF siRNA delivered by Stealth liposomes incorporating G2 PAMAM-cholesterol versus Metafectene? as a function of exposure time and siRNA concentration. Data in brief. 2016;8:1018-1023.
132	N Yonenaga, E Kenjo, T Asai, et al. RGD-based active targeting of novel polycation liposomes bearing siRNA for cancer treatment. J Control Release. 2012;160(2):177-181.
133	GR Dakwar, K Braeckmans, W Ceelen, SC De Smedt, K Remaut. Exploring the HYDRAtion method for loading siRNA on liposomes: the interplay between stability and biological activity in human undiluted ascites fluid. Drug Deliv Transl Res. 2017;7(2):241-251.
134	W Li, R Yan, Y Liu, et al. Co-delivery of Bmi1 small interfering RNA with ursolic acid by folate receptor-targeted cationic liposomes enhances anti-tumor activity of ursolic acid in vitro and in vivo. Drug Deliv. 2019;26(1):794-802.
135	HR Oh, HY Jo, JS Park, et al. Galactosylated liposomes for targeted co-delivery of doxorubicin/vimentin siRNA to hepatocellular carcinoma. Nanomaterials (Basel, Switzerland). 2016;6(8):141.
136	D Yang, Y Li, Y Qi, et al. Delivery of siRNA using cationic liposomes incorporating stearic acid-modified octa-arginine. Anticancer Res. 2016;36(7):3271-3276.
137	D Bedi, T Musacchio, OA Fagbohun, et al. Delivery of siRNA into breast cancer cells via phage fusion protein-targeted liposomes. Nanomedicine. 2011;7(3):315-323.
138	P Guo, J Yang, D Jia, MA Moses, DT Auguste. ICAM-1-targeted, Lcn2 siRNA-encapsulating liposomes are potent anti-angiogenic agents for triple negative breast cancer. Theranostics. 2016;6(1):1-13.
139	Y Yang, X Xie, X Xu, et al. Thermal and magnetic dual-responsive liposomes with a cell-penetrating peptide-siRNA conjugate for enhanced and targeted cancer therapy. Colloids Surf B Biointerfaces. 2016;146:607-615.
140	LC Gomes-da-Silva, JS Ramalho, MC Pedroso de Lima, S Sim?es, JN Moreira. Impact of anti-PLK1 siRNA-containing F3-targeted liposomes on the viability of both cancer and endothelial cells. Eur J Pharm Biopharm. 2013;85(3):356-364. Pt A.
141	B Xiang, DW Dong, NQ Shi, et al. PSA-responsive and PSMA-mediated multifunctional liposomes for targeted therapy of prostate cancer. Biomaterials. 2013;34(28):6976-6991.
142	T Al-Attar, SV Madihally. Targeted cancer treatment using a combination of siRNA-liposomes and resveratrol-electrospun fibers in co-cultures. Int J Pharm. 2019;569:118599.
143	S Bhunia, V Radha, A Chaudhuri. CDC20siRNA and paclitaxel co-loaded nanometric liposomes of a nipecotic acid-derived cationic amphiphile inhibit xenografted neuroblastoma. Nanoscale. 2017;9(3):1201-1212.
144	Y Yao, Z Su, Y Liang. Zhang N. pH-Sensitive carboxymethyl chitosan-modified cationic liposomes for sorafenib and siRNA co-delivery. Int J Nanomed. 2015;10:6185-6197.
145	N Khatri, D Baradia, I Vhora, M Rathi, A Misra. cRGD grafted liposomes containing inorganic nano-precipitate complexed siRNA for intracellular delivery in cancer cells. J Control Release. 2014;182:45-57.
146	Y Li, R Liu, J Yang, G Ma, Z Zhang, X Zhang. Dual sensitive and temporally controlled camptothecin prodrug liposomes codelivery of siRNA for high efficiency tumor therapy. Biomaterials. 2014;35(36):9731-9745.
147	T Yang, B Li, S Qi, et al. Co-delivery of doxorubicin and Bmi1 siRNA by folate receptor targeted liposomes exhibits enhanced anti-tumor effects in vitro and in vivo. Theranostics. 2014;4(11):1096-1111.
148	R Bernards, TR Brummelkamp, RL Beijersbergen. shRNA libraries and their use in cancer genetics. Nat Methods. 2006;3(9):701-706.
149	J Zhang, M Ding, K Xu, L Mao, J Zheng. shRNA-armed conditionally replicative adenoviruses: a promising approach for cancer therapy. Oncotarget. 2016;7(20):29824.
150	PJ Paddison, AA Caudy, GJ Hannon. Stable suppression of gene expression by RNAi in mammalian cells. Proc Natl Acad Sci USA. 2002;99(3):1443-1448.
151	G Sui, C Soohoo, EB Affar, et al. A DNA vector-based RNAi technology to suppress gene expression in mammalian cells. Proc Natl Acad Sci USA. 2002;99(8):5515-5520.
152	A El-Aneed. Current strategies in cancer gene therapy. Eur J Pharmacol. 2004;498(1-3):1-8.
153	DD Rao, JS Vorhies, N Senzer, J Nemunaitis. siRNA vs. shRNA: similarities and differences. Adv Drug Deliv Rev. 2009;61(9):746-759.
154	S Seraj, J Lee, HJ Ahn. Systemic delivery of Eg5 shRNA-expressing plasmids using PEGylated DC-Chol/DOPE cationic liposome: long-term silencing and anticancer effects in vivo. Biochem Pharmacol. 2019;166:192-202.
155	K Li, T Liu, J Chen, H Ni, W Li. Survivin in breast cancer-derived exosomes activates fibroblasts by up-regulating SOD1, whose feedback promotes cancer proliferation and metastasis. J Biol Chem. 2020;295(40):13737-13752.
156	P Yu, AX Li, XS Chen, et al. PKM2-c-Myc-survivin cascade regulates the cell proliferation, migration, and tamoxifen resistance in breast cancer. Front Pharmacol. 2020;11:550469.
157	F Li, MK Shanmugam, KS Siveen, et al. Garcinol sensitizes human head and neck carcinoma to cisplatin in a xenograft mouse model despite downregulation of proliferative biomarkers. Oncotarget. 2015;6(7):5147-5163.
158	R George, S Hehlgans, M Fleischmann, C Rodel, E Fokas, F Rodel. Advances in nanotechnology-based platforms for survivin-targeted drug discovery. Expert Opin Drug Dis. 2022;17(7):733-754.
159	M Suzuki, M Ohwada, T Tamada, S Tsuru. Thymidylate synthase activity as a prognostic factor in ovarian cancer. Oncology. 1994;51(4):334-338.
160	R Fujiwaki, K Hata, K Nakayama, M Fukumoto, K Miyazaki. Thymidylate synthase expression in epithelial ovarian cancer: relationship with thymidine phosphorylase expression and prognosis. Oncology. 2000;59(2):152-157.
161	K Iizuka, C Jin, K Eshima, MH Hong, K Eshima, M Fukushima. Anticancer activity of the intraperitoneal-delivered DFP-10825, the cationic liposome-conjugated RNAi molecule targeting thymidylate synthase, on peritoneal disseminated ovarian cancer xenograft model. Drug Des Dev Ther. 2018;12:673-683.
162	K Hynynen. Ultrasound for drug and gene delivery to the brain. Adv Drug Deliv Rev. 2008;60(10):1209-1217.
163	G Zhao, Q Huang, F Wang, et al. Targeted shRNA-loaded liposome complex combined with focused ultrasound for blood brain barrier disruption and suppressing glioma growth. Cancer Lett. 2018;418:147-158.
164	J Xu, Y Wang, Z Li, Q Wang, X Zhou, W Wu. Ultrasound-targeted microbubble destruction (UTMD) combined with liposome increases the effectiveness of suppressing proliferation, migration, invasion, and epithelial- mesenchymal transition (EMT) via targeting metadherin (MTDH) by ShRNA. Med Sci Monit. 2019;25:2640-2648.
165	W Xiao, W Zhang, H Huang, et al. Cancer targeted gene therapy for inhibition of melanoma lung metastasis with eIF3i shRNA loaded liposomes. Mol Pharm. 2020;17(1):229-238.
166	S Saavedra-Alonso, P Zapata-Benavides, AK Chavez-Escamilla, et al. WT1 shRNA delivery using transferrin-conjugated PEG liposomes in an in vivo model of melanoma. Exp Ther Med. 2016;12(6):3778-3784.
167	F Li, MK Shanmugam, L Chen, et al. Garcinol, a polyisoprenylated benzophenone modulates multiple proinflammatory signaling cascades leading to the suppression of growth and survival of head and neck carcinoma. Cancer Prev Res (Phila). 2013;6(8):843-854.
168	S Shishodia, G Sethi, KS Ahn, BB Aggarwal. Guggulsterone inhibits tumor cell proliferation, induces S-phase arrest, and promotes apoptosis through activation of c-Jun N-terminal kinase, suppression of Akt pathway, and downregulation of antiapoptotic gene products. Biochem Pharmacol. 2007;74(1):118-130.
169	W Wei, N Zarghami, M Abasi, YN Ertas, Y Pilehvar. Implantable magnetic nanofibers with ON–OFF switchable release of curcumin for possible local hyperthermic chemotherapy of melanoma. J Biomed Mater Res A. 2022;110(4):851-860.
170	KA Manu, MK Shanmugam, F Li, et al. Simvastatin sensitizes human gastric cancer xenograft in nude mice to capecitabine by suppressing nuclear factor-kappa B-regulated gene products. J Mol Med. 2014;92(3):267-276.
171	X Li, L Zhang, L Yu, et al. shRNA-mediated AMBRA1 knockdown reduces the cisplatin-induced autophagy and sensitizes ovarian cancer cells to cisplatin. J Toxicol Sci. 2016;41(1):45-53.
172	P Wang, N Yu, Y Wang, H Sun, Z Yang, S Zhou. Co-delivery of PLK1-specific shRNA and doxorubicin via core-crosslinked pH-sensitive and redox ultra-sensitive micelles for glioma therapy. J Mater Chem B. 2018;6(1):112-124.
173	N Templeton. Cationic liposomes as in vivo delivery vehicles. Curr Med Chem. 2003;10(14):1279-1287.
174	W-C Tseng, FR Haselton, TD Giorgio. Transfection by cationic liposomes using simultaneous single cell measurements of plasmid delivery and transgene expression. J Biol Chem. 1997;272(41):25641-25647.
175	JR Yazdi, M Tafaghodi, K Sadri, et al. Folate targeted PEGylated liposomes for the oral delivery of insulin: in vitro and in vivo studies. Colloids Surf B Biointerfaces. 2020;194:111203.
176	FM Menger, C Littau. Gemini-surfactants: synthesis and properties. J Am Chem Soc. 1991;113(4):1451-1452.
177	P Yang, J Singh, S Wettig, M Foldvari, RE Verrall, I Badea. Enhanced gene expression in epithelial cells transfected with amino acid-substituted gemini nanoparticles. Eur J Pharm Biopharm. 2010;75(3):311-320.
178	W Li, J Shi, C Zhang, et al. Co-delivery of thioredoxin 1 shRNA and doxorubicin by folate-targeted gemini surfactant-based cationic liposomes to sensitize hepatocellular carcinoma cells. J Mater Chem B. 2014;2(30):4901-4910.
179	Z Peng, C Wang, E Fang, X Lu, G Wang, Q Tong. Co-delivery of doxorubicin and SATB1 shRNA by thermosensitive magnetic cationic liposomes for gastric cancer therapy. PLoS One. 2014;9(3):e92924.
180	N Li, Y Mai, Q Liu, G Gou, J Yang. Docetaxel-loaded D-α-tocopheryl polyethylene glycol-1000 succinate liposomes improve lung cancer chemotherapy and reverse multidrug resistance. Drug Deliv Transl Res. 2021;11(1):131-141.
181	X Guo, J Zhang, Q Cai, et al. Acetic acid transporter-mediated, oral, multifunctional polymer liposomes for oral delivery of docetaxel. Colloids Surf B Biointerfaces. 2021;198:111499.
182	Y Kang, L Lu, J Lan, et al. Redox-responsive polymeric micelles formed by conjugating gambogic acid with bioreducible poly(amido amine)s for the co-delivery of docetaxel and MMP-9 shRNA. Acta Biomater. 2018;68:137-153.
183	S Yuan, T Qiao, X Zhuang, W Chen, N Xing, Q Zhang. Knockdown of the M2 isoform of pyruvate kinase (PKM2) with shRNA enhances the effect of docetaxel in human NSCLC cell lines in vitro. Yonsei Med J. 2016;57(6):1312-1323.
184	N Chowdhury, I Vhora, K Patel, R Doddapaneni, A Mondal, M Singh. Liposomes co-loaded with 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) shRNA plasmid and docetaxel for the treatment of non-small cell lung cancer. Pharm Res. 2017;34(11):2371-2384.
185	H Tian, S Liu, J Zhang, et al. Enhancement of cisplatin sensitivity in lung cancer xenografts by liposome-mediated delivery of the plasmid expressing small hairpin RNA targeting Survivin. J Biomed Nanotechnol. 2012;8(4):633-641.
186	H Chen, X Fan, Y Zhao, et al. Stimuli-responsive polysaccharide enveloped liposome for targeting and penetrating delivery of survivin-shRNA into breast tumor. ACS Appl Mater Interfaces. 2020;12(19):22074-22087.
187	R Swami, Y Kumar, D Chaudhari, et al. pH sensitive liposomes assisted specific and improved breast cancer therapy using co-delivery of SIRT1 shRNA and Docetaxel. Mater Sci Eng C Mater Biol Appl. 2021;120:111664.
188	Z Chen, K Liang, J Liu, et al. Enhancement of survivin gene downregulation and cell apoptosis by a novel combination: liposome microbubbles and ultrasound exposure. Med Oncol. 2009;26(4):491-500.
189	N Chauhan, A Dhasmana, M Jaggi, SC Chauhan, MM Yallapu. Mir-205: a potential biomedicine for cancer therapy. Cells. 2020;9(9):1957.
190	I Plantamura, A Cataldo, G Cosentino, MV Iorio. miR-205 in Breast Cancer: state of the Art. Int J Mol Sci. 2021;22(1):27.
191	C Zhou, X Zhao, S Duan. The role of miR-543 in human cancerous and noncancerous diseases. J Cell Physiol. 2021;236(1):15-26.
192	S Naghizadeh, A Mohammadi, PH Duijf, et al. The role of miR-34 in cancer drug resistance. J Cell Physiol. 2020;235(10):6424-6440.
193	M Ha, VN Kim. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol. 2014;15(8):509-524.
194	S Mirzaei, A Zarrabi, SE Asnaf, et al. The role of microRNA-338-3p in cancer: growth, invasion, chemoresistance, and mediators. Life Sci. 2021;268:119005.
195	MDA Paskeh, S Mirzaei, S Orouei, et al. Revealing the role of miRNA-489 as a new onco-suppressor factor in different cancers based on pre-clinical and clinical evidence. Int J Biol Macromol. 2021;191:727-737.
196	Z Yu, J Guo, M Hu, Y Gao, L Huang. Icaritin exacerbates mitophagy and synergizes with doxorubicin to induce immunogenic cell death in hepatocellular carcinoma. ACS Nano. 2020;14(4):4816-4828.
197	X Cui, D Zhou, Q Du, et al. MicroRNA200a enhances antitumor effects in combination with doxorubicin in hepatocellular carcinoma. Transl Oncol. 2020;13(10):100805.
198	H Xue, Z Yu, Y Liu, et al. Delivery of miR-375 and doxorubicin hydrochloride by lipid-coated hollow mesoporous silica nanoparticles to overcome multiple drug resistance in hepatocellular carcinoma. Int J Nanomed. 2017;12:5271-5287.
199	YP Fan, JZ Liao, YQ Lu, et al. MiR-375 and doxorubicin co-delivered by liposomes for combination therapy of hepatocellular carcinoma. Mol Ther Nucleic Acids. 2017;7:181-189.
200	H He, W Tian, H Chen, Y Deng. MicroRNA-101 sensitizes hepatocellular carcinoma cells to doxorubicin-induced apoptosis via targeting Mcl-1. Mol Med Rep. 2016;13(2):1923-1929.
201	F Xu, JZ Liao, GY Xiang, et al. MiR-101 and doxorubicin codelivered by liposomes suppressing malignant properties of hepatocellular carcinoma. Cancer Med. 2017;6(3):651-661.
202	X Dai, L Wang, A Deivasigamni, et al. A novel benzimidazole derivative, MBIC inhibits tumor growth and promotes apoptosis via activation of ROS-dependent JNK signaling pathway in hepatocellular carcinoma. Oncotarget. 2017;8(8):12831-12842.
203	F Ledezma-Gallegos, R Jurado, R Mir, LA Medina, L Mondragon-Fuentes, P Garcia-Lopez. Liposomes co-encapsulating cisplatin/mifepristone improve the effect on cervical cancer: in vitro and in vivo assessment. Pharmaceutics. 2020;12(9):897.
204	P Dana, S Bunthot, K Suktham, et al. Active targeting liposome-PLGA composite for cisplatin delivery against cervical cancer. Colloids Surf B Biointerfaces. 2020;196:111270.
205	L Wang, TT Liang. CD59 receptor targeted delivery of miRNA-1284 and cisplatin-loaded liposomes for effective therapeutic efficacy against cervical cancer cells. AMB Expr. 2020;10(1):54.
206	R Ippoliti, E Lendaro, I D'Agostino, et al. A chimeric saporin-transferrin conjugate compared to ricin toxin: role of the carrier in intracellular transport and toxicity. FASEB J. 1995;9(12):1220-1225.
207	X Li, L Ding, Y Xu, Y Wang, Q Ping. Targeted delivery of doxorubicin using stealth liposomes modified with transferrin. Int J Pharm. 2009;373(1-2):116-123.
208	K Sakurai, T Sohda, S Ueda, et al. Immunohistochemical demonstration of transferrin receptor 1 and 2 in human hepatocellular carcinoma tissue. Hepatogastroenterology. 2014;61(130):426-430.
209	W Zhang, F Peng, T Zhou, et al. Targeted delivery of chemically modified anti-miR-221 to hepatocellular carcinoma with negatively charged liposomes. Int J Nanomed. 2015;10:4825-4836.
210	HB Ruttala, N Chitrapriya, K Kaliraj, et al. Facile construction of bioreducible crosslinked polypeptide micelles for enhanced cancer combination therapy. Acta Biomater. 2017;63:135-149.
211	N Jan, A Madni, S Khan, et al. Biomimetic cell membrane-coated poly (lactic-co-glycolic acid) nanoparticles for biomedical applications. Bioeng Transl Med. 2022;8:e10441.
212	C Jing, L Yan, Z Wei, et al. Exogenous delivery of microRNA-134 (miR-134) using α-tocopherol-based PEGylated liposome for effective treatment in skin squamous cell carcinoma. Drug Deliv Transl Res. 2020;11(3):1000-1008.
213	S Sharma, V Rajendran, R Kulshreshtha, PC Ghosh. Enhanced efficacy of anti-miR-191 delivery through stearylamine liposome formulation for the treatment of breast cancer cells. Int J Pharm. 2017;530(1-2):387-400.
214	J Gao, J Sun, H Li, et al. Lyophilized HER2-specific PEGylated immunoliposomes for active siRNA gene silencing. Biomaterials. 2010;31(9):2655-2664.
215	K Ling, H Jiang, Y Li, X Tao, C Qiu, F-R Li. A self-assembling RNA aptamer-based graphene oxide sensor for the turn-on detection of theophylline in serum. Biosens Bioelectron. 2016;86:8-13.
216	M Herlyn, Z Steplewski, D Herlyn, H Koprowski. Colorectal carcinoma-specific antigen: detection by means of monoclonal antibodies. Proc Natl Acad Sci USA. 1979;76(3):1438-1442.
217	K Lund, M Bostad, E Skarpen, et al. The novel EpCAM-targeting monoclonal antibody 3–17I linked to saporin is highly cytotoxic after photochemical internalization in breast, pancreas and colon cancer cell lines. MAbs. 2014;6:1038-1050.
218	PT Went, A Lugli, S Meier, et al. Frequent EpCam protein expression in human carcinomas. Hum Pathol. 2004;35(1):122-128.
219	Y Zhao, J Xu, VM Le, et al. EpCAM aptamer-functionalized cationic liposome-based nanoparticles loaded with miR-139-5p for targeted therapy in colorectal cancer. Mol Pharm. 2019;16(11):4696-4710.
220	L Jiang, H Wang, S Chen. Aptamer (AS1411)-Conjugated liposome for enhanced therapeutic efficacy of miRNA-29b in ovarian cancer. J Nanosci Nanotechnol. 2020;20(4):2025-2031.
221	J Tao, WF Ding, XH Che, et al. Optimization of a cationic liposome-based gene delivery system for the application of miR-145 in anticancer therapeutics. Int J Mol Med. 2016;37(5):1345-1354.
222	F Huang, F Zhao, LP Liang, et al. Optomizing transfection efficiency of cervical cancer cells transfected by cationic liposomes lipofectamineTM2000. Asian Pac J Cancer Prev. 2015;16(17):7749-7754.
223	B Xu, J Mei, W Ji, et al. LncRNA SNHG3, a potential oncogene in human cancers. Cancer Cell Int. 2020;20(1):1-11.
224	C Shen, C Yang, B Xia, M You. Long non-coding RNAs: emerging regulators for chemo/immunotherapy resistance in cancer stem cells. Cancer Lett. 2021;500:244-252.
225	M Wu, X Zhang, X Han, V Pandey, PE Lobie, T Zhu. The potential of long noncoding RNAs for precision medicine in human cancer. Cancer Lett. 2020;501:12-19.
226	EE Robless, JA Howard, I Casari, M Falasca. Exosomal long non-coding RNAs in the diagnosis and oncogenesis of pancreatic cancer. Cancer Lett. 2021;501:55-65.
227	Z Ma, YY Wang, HW Xin, et al. The expanding roles of long non-coding RNAs in the regulation of cancer stem cells. Int J Biochem Cell Biol. 2019;108:17-20.
228	JT Cheng, L Wang, H Wang, et al. Insights into biological role of LncRNAs in epithelial-mesenchymal transition. Cells. 2019;8(10):1178.
229	S Kansara, V Pandey, PE Lobie, G Sethi, M Garg, AK Pandey. Mechanistic involvement of long non-coding RNAs in oncotherapeutics resistance in triple-negative breast cancer. Cells. 2020;9(6):1511.
230	G Pandya, A Kirtonia, G Sethi, AK Pandey, M Garg. The implication of long non-coding RNAs in the diagnosis, pathogenesis and drug resistance of pancreatic ductal adenocarcinoma and their possible therapeutic potential. Biochim Biophys Acta Rev Cancer. 2020;1874(2):188423.
231	K Gala, E Khattar. Long non-coding RNAs at work on telomeres: functions and implications in cancer therapy. Cancer Lett. 2021;502:120-132.
232	V Bhardwaj, YQ Tan, MM Wu, et al. Long non-coding RNAs in recurrent ovarian cancer: theranostic perspectives. Cancer Lett. 2021;502:97-107.
233	YWS Lim, X Xiang, M Garg, et al. The double-edged sword of H19 lncRNA: insights into cancer therapy. Cancer Lett. 2020;500:253-262.
234	S Ashrafizaveh, M Ashrafizadeh, A Zarrabi, et al. Long non-coding RNA in the doxorubicin resistance of cancer cells. Cancer Lett. 2021;508:104-114.
235	H Ye, X Chu, Z Cao, et al. A novel targeted therapy system for cervical cancer: co-delivery system of antisense LncRNA of MDC1 and oxaliplatin magnetic thermosensitive cationic liposome drug carrier. Int J Nanomed. 2021;16:1051-1066.
236	W Yu, Y Qiao, X Tang, et al. Tumor suppressor long non-coding RNA, MT1DP is negatively regulated by YAP and Runx2 to inhibit FoxA1 in liver cancer cells. Cell Signal. 2014;26(12):2961-2968.
237	C Gai, C Liu, X Wu, et al. MT1DP loaded by folate-modified liposomes sensitizes erastin-induced ferroptosis via regulating miR-365a-3p/NRF2 axis in non-small cell lung cancer cells. Cell Death Dis. 2020;11(9):751.
238	Q Yu, Y Qiu, X Wang, et al. Efficient siRNA transfer to knockdown a placenta specific lncRNA using RGD-modified nano-liposome: a new preeclampsia-like mouse model. Int J Pharm. 2018;546(1-2):115-124.
239	X Song, C Liu, N Wang, et al. Delivery of CRISPR/Cas systems for cancer gene therapy and immunotherapy. Adv Drug Deliv Rev. 2021;168:158-180.
240	D Liu, X Zhao, A Tang, et al. CRISPR screen in mechanism and target discovery for cancer immunotherapy. Biochim Biophys Acta Rev Cancer. 2020;1874(1):188378-188378.
241	H Xing, L-H Meng. CRISPR-cas9: a powerful tool towards precision medicine in cancer treatment. Acta Pharmacol Sin. 2020;41(5):583-587.
242	M Jinek, K Chylinski, I Fonfara, M Hauer, JA Doudna, E Charpentier. A programmable dual-RNA–guided DNA endonuclease in adaptive bacterial immunity. Science. 2012;337(6096):816-821.
243	MR O'Connell, BL Oakes, SH Sternberg, A East-Seletsky, M Kaplan, JA Doudna. Programmable RNA recognition and cleavage by CRISPR/Cas9. Nature. 2014;516(7530):263-266.
244	JE Garneau, M-è Dupuis, M Villion, et al. The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA. Nature. 2010;468(7320):67-71.
245	G Gasiunas, R Barrangou, P Horvath, V Siksnys. Cas9–crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria. Proc Natl Acad Sci USA. 2012;109(39):E2579-E2586.
246	CR Hale, P Zhao, S Olson, et al. RNA-guided RNA cleavage by a CRISPR RNA-Cas protein complex. Cell. 2009;139(5):945-956.
247	A Hazafa, M Mumtaz, MF Farooq, et al. CRISPR/Cas9: a powerful genome editing technique for the treatment of cancer cells with present challenges and future directions. Life Sci. 2020;263:118525.
248	W Zhang, Y Liu, X Zhou, R Zhao, H Wang. Applications of CRISPR-Cas9 in gynecological cancer research. Clin Genet. 2020;97(6):827-834.
249	G Sharma, AR Sharma, M Bhattacharya, SS Lee, C Chakraborty. CRISPR-Cas9: a preclinical and clinical perspective for the treatment of human diseases. Mol Ther. 2021;29(2):571-586.
250	Z Liu, Z Liao, Y Chen, L Zhou, W Huangting, H Xiao. Research on CRISPR/system in major cancers and its potential in cancer treatments. Clin Transl Oncol. 2021;23(3):425-433.
251	D Wang, F Zhang, G Gao. CRISPR-based therapeutic genome editing: strategies and in vivo delivery by AAV vectors. Cell. 2020;181(1):136-150.
252	Q Cheng, T Wei, L Farbiak, LT Johnson, SA Dilliard, DJ Siegwart. Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR-Cas gene editing. Nat Nanotechnol. 2020;15(4):313-320.
253	CF Xu, GJ Chen, YL Luo, et al. Rational designs of in vivo CRISPR-Cas delivery systems. Adv Drug Deliv Rev. 2021;168:3-29.
254	RS Schuh, é Poletto, FNS Fachel, U Matte, G Baldo, HF Teixeira. Physicochemical properties of cationic nanoemulsions and liposomes obtained by microfluidization complexed with a single plasmid or along with an oligonucleotide: implications for CRISPR/Cas technology. J Colloid Interface Sci. 2018;530:243-255.
255	YA Aksoy, B Yang, W Chen, et al. Spatial and temporal control of CRISPR-Cas9-mediated gene editing delivered via a light-triggered liposome system. ACS Appl Mater Interfaces. 2020;12(47):52433-52444.
256	S Zhen, Y Liu, J Lu, et al. Human papillomavirus oncogene manipulation using clustered regularly interspersed short palindromic repeats/Cas9 delivered by pH-sensitive cationic liposomes. Hum Gene Ther. 2020;31(5-6):309-324.
257	JA Zuris, DB Thompson, Y Shu, et al. Cationic lipid-mediated delivery of proteins enables efficient protein-based genome editing in vitro and in vivo. Nat Biotechnol. 2015;33(1):73-80.
258	W Sun, W Ji, JM Hall, et al. Self-assembled DNA nanoclews for the efficient delivery of CRISPR-Cas9 for genome editing. Angew Chem Int Ed Engl. 2015;54(41):12029-12033.
259	E Kouranova, K Forbes, G Zhao, et al. CRISPRs for optimal targeting: delivery of CRISPR components as DNA, RNA, and protein into cultured cells and single-cell embryos. Hum Gene Ther. 2016;27(6):464-475.
260	JF Deeken, W L?scher. The blood-brain barrier and cancer: transporters, treatment, and Trojan horses. Clin Cancer Res. 2007;13(6):1663-1674.
261	J Zhou, K-B Atsina, BT Himes, GW Strohbehn, WM Saltzman. Novel delivery strategies for glioblastoma. Cancer J (Sudbury, Mass). 2012;18(1):89-99.
262	Z Chen, F Liu, Y Chen, et al. Targeted delivery of CRISPR/Cas9-mediated cancer gene therapy via liposome-templated hydrogel nanoparticles. Adv Funct Mater. 2017;27(46):1703036.
263	E Montaudon, J Nikitorowicz-Buniak, L Sourd, et al. PLK1 inhibition exhibits strong anti-tumoral activity in CCND1-driven breast cancer metastases with acquired palbociclib resistance. Nat Commun. 2020;11(1):4053.
264	S Su, G Chhabra, MA Ndiaye, et al. PLK1 and NOTCH positively correlate in melanoma and their combined inhibition results in synergistic modulations of key melanoma pathways. Mol Cancer Ther. 2021;20(1):161-172.
265	S Zhen, Y Takahashi, S Narita, YC Yang, X Li. Targeted delivery of CRISPR/Cas9 to prostate cancer by modified gRNA using a flexible aptamer-cationic liposome. Oncotarget. 2017;8(6):9375-9387.
266	H Hayashi, K Nakagawa. Combination therapy with PD-1 or PD-L1 inhibitors for cancer. Int J Clin Oncol. 2020;25(5):818-830.
267	S Kumagai, Y Togashi, T Kamada, et al. The PD-1 expression balance between effector and regulatory T cells predicts the clinical efficacy of PD-1 blockade therapies. Nat Immunol. 2020;21(11):1346-1358.
268	X Chen, X Pan, W Zhang, et al. Epigenetic strategies synergize with PD-L1/PD-1 targeted cancer immunotherapies to enhance antitumor responses. Acta Pharm Sin B. 2020;10(5):723-733.
269	T Nakazawa, A Natsume, F Nishimura, et al. Effect of CRISPR/Cas9-mediated PD-1-disrupted primary human third-generation CAR-T cells targeting EGFRvIII on in vitro human glioblastoma cell growth. Cells. 2020;9(4):998.
270	B Luo, Y Zhan, M Luo, et al. Engineering of α-PD-1 antibody-expressing long-lived plasma cells by CRISPR/Cas9-mediated targeted gene integration. Cell Death Dis. 2020;11(11):973.
271	S Lu, N Yang, J He, et al. Generation of cancer-specific cytotoxic PD-1(-) T cells using liposome-encapsulated CRISPR/Cas system with dendritic/tumor fusion cells. J Biomed Nanotechnol. 2019;15(3):593-601.
272	L Jubair, AK Lam, S Fallaha, NAJ McMillan. CRISPR/Cas9-loaded stealth liposomes effectively cleared established HPV16-driven tumours in syngeneic mice. PLoS One. 2021;16(1):e0223288.
273	VP Zhdanov. Intracellular RNA delivery by lipid nanoparticles: diffusion, degradation, and release. Biosystems. 2019;185:104032.
274	O Zelphati, FC Szoka Jr. Mechanism of oligonucleotide release from cationic liposomes. Proc Natl Acad Sci USA. 1996;93(21):11493-11498.
275	N Kamaly, B Yameen, J Wu, OC Farokhzad. Degradable controlled-release polymers and polymeric nanoparticles: mechanisms of controlling drug release. Chem Rev. 2016;116(4):2602-2663.
276	J Sch?fer, S H?bel, U Bakowsky, A Aigner. Liposome–polyethylenimine complexes for enhanced DNA and siRNA delivery. Biomaterials. 2010;31(26):6892-6900.
277	T Yang, T Bantegui, K Pike, R Bloom, R Phipps, S Bai. In vitro evaluation of optimized liposomes for delivery of small interfering RNA. J Liposome Res. 2014;24(4):270-279.
278	Y Hattori, M Nakamura, N Takeuchi, et al. Effect of cationic lipid in cationic liposomes on siRNA delivery into the lung by intravenous injection of cationic lipoplex. J Drug Target. 2019;27(2):217-227.
279	L Zhang, S Liu, H Liu, et al. Versatile cationic liposomes for RIP3 overexpression in colon cancer therapy and RIP3 downregulation in acute pancreatitis therapy. J Drug Target. 2020;28(6):627-642.
280	M Hashemi, F Ghadyani, S Hasani, et al. Nanoliposomes for doxorubicin delivery: reversing drug resistance, stimuli-responsive carriers and clinical translation. J Drug Deliv Sci Technol. 2023;80:104112.
281	RN Majzoub, C-L Chan, KK Ewert, et al. Uptake and transfection efficiency of PEGylated cationic liposome–DNA complexes with and without RGD-tagging. Biomaterials. 2014;35(18):4996-5005.
282	R Pattipeiluhu, S Crielaard, I Klein-Schiphorst, BI Florea, A Kros, F Campbell. Unbiased identification of the liposome protein corona using photoaffinity-based chemoproteomics. ACS Cent Sci. 2020;6(4):535-545.
283	CD Walkey, WC Chan. Understanding and controlling the interaction of nanomaterials with proteins in a physiological environment. Chem Soc Rev. 2012;41(7):2780-2799.
284	AE Nel, L M?dler, D Velegol, et al. Understanding biophysicochemical interactions at the nano-bio interface. Nat Mater. 2009;8(7):543-557.
285	GJN Caracciolo. Clinically approved liposomal nanomedicines: lessons learned from the biomolecular corona. Nanoscale. 2018;10(9):4167-4172.
286	AL Barrán-Berdón, D Pozzi, G Caracciolo, et al. Time evolution of nanoparticle–protein corona in human plasma: relevance for targeted drug delivery. Langmuir. 2013;29(21):6485-6494.
287	Y Zhu, Y Meng, Y Zhao, et al. Toxicological exploration of peptide-based cationic liposomes in siRNA delivery. Colloids Surf B. 2019;179:66-76.
288	Y Zhang, B Chu, Q Fan, X Song, Q Xu, Y Qu. M2-type macrophage-targeted delivery of IKKβ siRNA induces M2-to-M1 repolarization for CNV gene therapy. Nanomed Nanotechnol Biol Med. 2024;57:102740.
289	B Qin, M Jiang, X Li, et al. Oxygen nanocarrier broke the hypoxia trap of solid tumors and rescued transfection efficiency for gene therapy. J Nanobiotechnol. 2021;19:1-14.
290	S Arora, B Layek, J Singh. Design and validation of liposomal ApoE2 gene delivery system to evade blood–brain barrier for effective treatment of Alzheimer's disease. Mol Pharm. 2020;18(2):714-725.