Anti-breast Cancer Activity of pH-responsive Nanogel Loaded with Curcumin

Abstract

We prepared curcumin (Cur)/carboxymethyl-β-cyclodextrin (CM-β-CD) complex by grinding method. According to the characteristics of the tumor microenvironment, a pH-responsive nanogel loaded with Cur was designed and prepared (by CM-β-CD and chitosan) and consequently characterized by DLS, TEM, FTIR, ¹H NMR, SEM, etc. In vitro release results show that Cur-loaded Chitosan-CM-β-CD nanogel (Cur-CS-CM-β-CD) released Cur rapidly under acidic conditions, and its cumulative release rate is 41%, 56% and 67% at pH 7.4, 6.5 and 5.5, respectively. The cell inhibition rate of Cur-CS-CM-β-CD on MCF-7 cell lines was detected by the MTT assay. The results suggest the cell inhibition rate of Cur-CS-CM-β-CD is (50.2±2.5)% at 10 µM, (98.3±1.2)% at 40 µM and (97.5±1.2)% at 80 µM, respectively. It is revealed that the pH-responsive nanogel loaded Cur can effectively inhibit the growth of breast cancer cells and has the potential for clinical application.

References

[1] ZhouB J, LiM, XuX M, et al.. Integrin α2β1 Targeting Dgea-modified Liposomal Doxorubicin Enhances Antitumor Efficacy Against Breast Cancer[J]. Mol. Pharmaceutics, 2021, 18(7): 2634-2646

[2] CrozierJ A, SwaikaA, Moreno-AspitiaA. Adjuvant Chemotherapy in Breast Cancer: To Use or Not to Use, the Anthracyclines[J]. World. J. Clin. Oncol., 2014, 5(3): 529-538

[3] Abdel-RazeqH, AttigaF, MansourA. Cancer Care in Jordan[J]. Hematol. Oncol. Stem. Cell. Ther., 2015, 8(2): 64-70

[4] TagdeP, KulkarniG T, MishraD K, et al.. Recent Advances in Folic Acid Engineered Nanocarriers for Treatment of Breast Cancer[J]. J. Drug. Deliv. Sci. Tec., 2020, 56: 101 613

[5] SzalontaiK, GemesN, FurakJ, et al.. Chronic Obstructive Pulmonary Disease: Epidemiology, Biomarkers, and Paving the Way to Lung Cancer[J]. J. Clin. Med., 2021, 10(13): 2 889

[6] SheervalilouR, LotfiH, ShirvalilooM, et al.. Circulating MiR-10b, MiR-1 and MiR-30a Expression Profiles in Lung Cancer: Possible Correlation with Clinico-pathologic Characteristics and Lung Cancer Detection[J]. Int. J. Mol. Cell. Med., 2019, 8(2): 118-129

[7] VoudouriK, BerdiakiA, TzardiM, et al.. Insulin-like Growth Factor and Epidermal Growth Factor Signaling in Breast Cancer Cell Growth: Focus on Endocrine Resistant Disease[J]. Anal. Cell. Pathol., 2015, 2015: 975 495

[8] HwangS Y, ParkS, KwonY. Recent Therapeutic Trends and Promising Targets in Triple Negative Breast Cancer[J]. Pharmacol. Ther., 2019, 199: 30-57

[9] Planes-LaineG, RochigneuxP, BertucciF, et al.. PD-1/PD-L1 Targeting in Breast Cancer: The First Clinical Evidences are Emerging-a Literature Review[J]. Cancers, 2019, 11(7): 1 033

[10] ZareieB, RasouliM A, PoorolajalJ. Risk of Primary Lung Cancer After Breast Cancer Radiotherapy: A Systematic Review and Meta-analysis[J]. Breast. Cancer-Tokyo., 2022, 29(2): 361-367

[11] NeamtuI, RusuA G, DiaconuA, et al.. Basic Concepts and Recent Advances in Nanogels as Carriers for Medical Applications[J]. Drug. Deliv., 2017, 24(1): 539-557

[12] DuX J, GaoY T, KangQ, et al.. Design and Applications of Tumor Microenvironment-responsive Nanogels as Drug Carriers[J]. Front. Bioeng. Biotech., 2021, 9: 771 851

[13] Van ThienenT G, RaemdonckK, DemeesterJ, et al.. Protein Release from Biodegradable Dextran Nanogels[J]. Langmuir, 2007, 23(19): 9794-9801

[14] MoiseevR V, KaldybekovD B, FilippovS K, et al.. Maleimide-decorated Pegylated Mucoadhesive Liposomes for Ocular Drug Delivery[J]. Langmuir, 2022, 38(45): 13870-13879

[15] ShinU, KimJ, LeeJ, et al.. Development of ⁶⁴Cu-loaded Perfluoropentane Nanodroplet: A Potential Tumor Theragnostic Nano-carrier and Dual-modality PET-ultrasound Imaging Agents[J]. Ultrasound. Med. Biol., 2020, 46(10): 2775-2784

[16] DawreS, WaghelaS, SaraogiG. Statistically Designed Vitamin D3 Encapsulated PLGA Microspheres Dispersed in Thermoresponsive In-situ Gel for Nasal Delivery[J]. J. Drug. Deliv. Sci. Tec., 2022, 75: 103 688

[17] Doan-NguyenT P, NatsathapornP, JenjobR, et al.. Regulating Payload Release from Hybrid Nanocapsules with Dual Silica/polycaprolactone Shells[J]. Langmuir, 2019, 35(35): 11389-11396

[18] CassanoR, De AmicisF, ServidioC, et al.. Preparation, Characterization and in Vitro Evaluation of Resveratrol-loaded Nanospheres Potentially Useful for Human Breast Carcinoma[J]. J. Drug. Deliv. Sci. Technol., 2020, 57: 101 748

[19] LiZ Y, QinX Y, GuoL Y, et al.. Poly (acrylic acid) Microspheres Loaded with Superparamagnetic Iron Oxide Nanoparticles for Transcatheter Arterial Embolization and MRI Detectability: In Vitro and in Vivo Evaluation[J]. Int. J. Pharm., 2017, 527(1–2): 31-41

[20] LiuZ Q, SmartJ D, PannalaA S. Recent Developments in Formulation Design for Improving Oral Bioavailability of Curcumin: A Review[J]. J. Drug. Deliv. Sci. Technol., 2020, 60: 102 082

[21] SrimalR C, DhawanB N. Pharmacology of Diferuloyl Methane (Curcumin), a Non-steroidal Anti-inflammatory Agent[J]. J. Pharm. Pharmacol., 1973, 25(6): 447-452

[22] PrasadS, TyagiA K. Curcumin and Its Analogues: A Potential Natural Compound Against HIV Infection and AIDS[J]. Food. Funct., 2015, 6(11): 3412-3419

[23] KabirM T, RahmanM H, AkterR, et al.. Potential Role of Curcumin and Its Nanoformulations to Treat Various Types of Cancers[J]. Biomolecules, 2021, 11(3): 392

[24] LiM J, GuoT T, LinJ Y, et al.. Curcumin Inhibits the Invasion and Metastasis of Triple Negative Breast Cancer via Hedgehog/Gli1 Signaling Pathway[J]. J. Ethnopharmacol., 2022, 283: 114 689

[25] LinX K, WangL H, ZhaoL Q. Curcumin Micelles Suppress Gastric Tumor Cell Growth by Upregulating ROS Generation, Disrupting Redox Equilibrium and Affecting Mitochondrial Bioenergetics[J]. Food. Funct., 2020, 11(5): 4146-4159

[26] DouH Q, ShenR H, TaoJ X, et al.. Curcumin Suppresses the Colon Cancer Proliferation by Inhibiting Wnt/β-Catenin Pathways via MiR-130A[J]. Front. Pharmacol., 2017, 8: 877

[27] YanC Y, ShiW G, GuJ W, et al.. Design of a Novel Nucleus-targeted NLS-KALA-SA Nanocarrier to Delivery Poorly Water-soluble Anti-tumor Drug for Lung Cancer Treatment[J]. J. Pharm. Sci., 2021, 110(6): 2432-2441

[28] Keyvani-GhamsariS, KhorsandiK, GulA. Curcumin Effect on Cancer Cells’ Multidrug Resistance: An Update[J]. Phytother. Res., 2020, 34(10): 2534-2556

[29] SalihM, OmoloC A, AgrawalN, et al.. Supramolecular Amphiphiles of Beta-cyclodextrin and Oleylamine for Enhancement of Vancomycin Delivery[J]. Int. J. Pharm., 2020, 574: 118 881

[30] KhanK U, MinhasM U, BadshahS F, et al.. β-cyclodextrin Modification by Cross-linking Polymerization as Highly Porous Nanomatrices for Olanzapine Solubility Improvement; Synthesis, Characterization and Bio-compatibility Evaluation[J]. J. Drug. Deliv. Sci. Technol., 2022, 67: 102 952

[31] LiN, WangN, WuT N, et al.. Preparation of Curcumin-hydroxypropyl-β-cyclodextrin Inclusion Complex by Cosolvency-lyophilization Procedure to Enhance Oral Bioavailability of the Drug[J]. Drug. Dev. Ind. Pharm., 2018, 44(12): 1966-1974

[32] BragaS S. Cyclodextrin Superstructures for Drug Delivery[J]. J. Drug. Delivery Sci. Technol., 2022, 75: 103 650

[33] KhattabiA M, TalibW H, AlqdeimatD A. A Targeted Drug Delivery System of Anti-cancer Agents Based on Folic Acid-cyclodextrin-long Polymer Functionalized Silica Nanoparticles[J]. J. Drug. Deli. Sci. Technol., 2017, 41: 367-374

[34] ScharlT, CadranelA, HainesP. Fine-tuning the Assemblies of Carbon Nanodots and Porphyrins[J]. Chem. Commun., 2018, 54(82): 11642-11644

[35] WangY W, QinF, LuM, et al.. The Screening and Evaluating of Chitosan/β-cyclodextrin Nanoparticles for Effective Delivery Mitoxantrone Hydrochloride[J]. Polym. Sci, Ser. A, 2017, 59(3): 376-383

[36] JahedV, ZarrabiA, BordbarA K, et al.. NMR (¹H, ROESY) Spectroscopic and Molecular Modelling Investigations of Supramolecular Complex of β-cyclodextrin and Curcumin[J]. Food. Chem., 2014, 165: 241-246

[37] VerzaB S, van den BeuckenJ J J P, BrandtJ V. A Long-term Controlled Drug-delivery with Anionic Beta Cyclodextrin Complex in Layer-by-layer Coating for Percutaneous Implants Devices[J]. Carbohydr. Polym., 2021, 257: 117 604

[38] QiX J, CuiY L, WangQ S, et al.. Preparation and Characterization of Guanidinylated Chitosan/β-Glycerophosphate Thermo-Sensitive Hydrogel[J]. Adv. Mater. Res., 2013, 749: 182-185

[39] BadruddozaA Z M, TayA S H, TanP Y, et al.. Carboxymethyl-β-cyclodextrin Conjugated Magnetic Nanoparticles as Nano-adsorbents for Removal of Copper Ions: Synthesis and Adsorption Studies[J]. J. Hazard. Mater., 2011, 185(2–3): 1177-1186

[40] ShenH J, LiF, WangD X, et al.. Chitosan-alginate BSA-gel-capsules for Local Chemotherapy Against Drug-resistant Breast Cancer[J]. Drug Des. Dev. Ther., 2018, 12: 921-934

[41] SarikaP R, NirmalaR J. Curcumin Loaded Gum Arabic Aldehyde-gelatin Nanogels for Breast Cancer Therapy[J]. Mater. Sci. Eng. C. Mater. Biol. Appl., 2016, 65: 331-337

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