Immunological effects of nano-enabled hyperthermia for solid tumors: opportunity and challenge

Abstract

Compared to conventional hyperthermia that is limited by low selectivity and severe side effects, nano-enabled hyperthermia yields great potentials to tackle these limitations for cancer treatment. Another major advance is the observation of immunological responses associated with nano-enabled hyperthermia, which introduces a new avenue, allowing a potential paradigm shift from the acutely effective and cytotoxicity-centric response to the next-phase discovery, i.e., long-lasting and/or systemic anti-tumor immunity. This perspective first discusses the temperature-gradient and the spatially-structured immunological landscape in solid tumors receiving nano-enabled hyperthermia. This includes the discussion about underlying mechanism such as immunogenic cell death, which initiates a profound immunological chain reaction. In order to propagate the immune activation as a viable therapeutic principle, we further discussed the tumor type-specific complexity in the immunological tumor microenvironment, including the creative design of nano-enabled combination therapy to synergize with nano-enabled hyperthermia.

Graphical abstract

Keywords

nano-enabled hyperthermia / immunogenic cell death / heterogeneous immunological landscape / tumor microenvironment

References

[1] Chu K F, Dupuy D E. Thermal ablation of tumours: biological mechanisms and advances in therapy. Nature Reviews. Cancer, 2014, 14(3): 199–208

[2] Falk M H, Issels R D. Hyperthermia in oncology. International Journal of Hyperthermia, 2001, 17(1): 1–18

[3] Field S B, Bleehen N M. Hyperthermia in the treatment of cancer. Cancer Treatment Reviews, 1979, 6(2): 63–94

[4] Wust P, Hildebrandt B, Sreenivasa G, Rau B, Gellermann J, Riess H, Felix R, Schlag P M. Hyperthermia in combined treatment of cancer. Lancet. Oncology, 2002, 3(8): 487–497

[5] Cherukuri P, Glazer E S, Curley S A. Targeted hyperthermia using metal nanoparticles. Advanced Drug Delivery Reviews, 2010, 62(3): 339–345

[6] Thiesen B, Jordan A. Clinical applications of magnetic nanoparticles for hyperthermia. International Journal of Hyperthermia, 2008, 24(6): 467–474

[7] Beik J, Abed Z, Ghoreishi F S, Hosseini-Nami S, Mehrzadi S, Shakeri-Zadeh A, Kamrava S K. Nanotechnology in hyperthermia cancer therapy: from fundamental principles to advanced applications. Journal of Controlled Release, 2016, 235: 205–221

[8] Huang X, Jain P K, El-Sayed I H, El-Sayed M A. Plasmonic photothermal therapy (PPTT) using gold nanoparticles. Lasers in Medical Science, 2008, 23(3): 217–228

[9] Jaque D, Maestro L M, Del Rosal B, Haro Gonzalez P, Benayas A, Plaza J, Rodriguez E M, Sole J. Nanoparticles for photothermal therapies. Nanoscale, 2014, 6(16): 9494–9530

[10] Liu X, Huang N, Li H, Wang H, Jin Q, Ji J. Multidentate polyethylene glycol modified gold nanorods for in vivo near-infrared photothermal cancer therapy. ACS Applied Materials & Interfaces, 2014, 6(8): 5657–5668

[11] Kim H C, Kim E, Jeong S W, Ha T L, Park S I, Lee S G, Lee S J, Lee S W. Magnetic nanoparticle-conjugated polymeric micelles for combined hyperthermia and chemotherapy. Nanoscale, 2015, 7(39): 16470–16480

[12] Tamarov K P, Osminkina L A, Zinovyev S V, Maximova K A, Kargina J V, Gongalsky M B, Ryabchikov Y, Al Kattan A, Sviridov A P, Sentis M. Radio frequency radiation-induced hyperthermia using Si nanoparticle-based sensitizers for mild cancer therapy. Scientific Reports, 2014, 4(1): 1–7

[13] Kumar R, Chauhan A, Jha S K, Kuanr B K. Localized cancer treatment by radio-frequency hyperthermia using magnetic nanoparticles immobilized on graphene oxide: from novel synthesis to in vitro studies. Journal of Materials Chemistry. B, Materials for Biology and Medicine, 2018, 6(33): 5385–5399

[14] Cardinal J, Klune J R, Chory E, Jeyabalan G, Kanzius J S, Nalesnik M, Geller D A. Noninvasive radiofrequency ablation of cancer targeted by gold nanoparticles. Surgery, 2008, 144(2): 125–132

[15] Kaczmarek K, Hornowski T, Kubovcikova M, Timko M, Koralewski M, Jozefczak A. Heating induced by therapeutic ultrasound in the presence of magnetic nanoparticles. ACS Applied Materials & Interfaces, 2018, 10(14): 11554–11564

[16] Beik J, Abed Z, Shakeri-Zadeh A, Nourbakhsh M, Shiran M B. Evaluation of the sonosensitizing properties of nano-graphene oxide in comparison with iron oxide and gold nanoparticles. Physica E, Low-Dimensional Systems and Nanostructures, 2016, 81: 308–314

[17] Devarakonda S B, Myers M R, Lanier M, Dumoulin C, Banerjee R K. Assessment of gold nanoparticle-mediated-enhanced hyperthermia using MR-guided high-intensity focused ultrasound ablation procedure. Nano Letters, 2017, 17(4): 2532–2538

[18] Hildebrandt B, Wust P, Ahlers O, Dieing A, Sreenivasa G, Kerner T, Felix R, Riess H. The cellular and molecular basis of hyperthermia. Critical Reviews in Oncology/Hematology, 2002, 43(1): 33–56

[19] Lepock J R. Cellular effects of hyperthermia: relevance to the minimum dose for thermal damage. International Journal of Hyperthermia, 2003, 19(3): 252–266

[20] Roti J L. Cellular responses to hyperthermia (40 °C–46 °C): cell killing and molecular events. International Journal of Hyperthermia, 2008, 24(1): 3–15

[21] Fairchild K D, Viscardi R M, Hester L, Singh I S, Hasday J D. Effects of hypothermia and hyperthermia on cytokine production by cultured human mononuclear phagocytes from adults and newborns. Journal of Interferon & Cytokine Research, 2000, 20(12): 1049–1055

[22] Ito A, Honda H, Kobayashi T. Cancer immunotherapy based on intracellular hyperthermia using magnetite nanoparticles: a novel concept of “heat-controlled necrosis” with heat shock protein expression. Cancer Immunology, Immunotherapy, 2006, 55(3): 320–328

[23] Ito A, Shinkai M, Honda H, Yoshikawa K, Saga S, Wakabayashi T, Yoshida J, Kobayashi T. Heat shock protein 70 expression induces antitumor immunity during intracellular hyperthermia using magnetite nanoparticles. Cancer Immunology, Immunotherapy, 2003, 52(2): 80–88

[24] Galluzzi L, Buqué A, Kepp O, Zitvogel L, Kroemer G. Immunogenic cell death in cancer and infectious disease. Nature Reviews. Immunology, 2017, 17(2): 97–111

[25] Todryk S, Melcher A, Dalgleish A, Vile R G. Heat shock proteins refine the danger theory. Immunology, 2000, 99(3): 334–337

[26] Zhang Z, Wang J, Chen C. Gold nanorods based platforms for light-mediated theranostics. Theranostics, 2013, 3(3): 223–238

[27] Dickerson E B, Dreaden E C, Huang X, El Sayed I H, Chu H, Pushpanketh S, McDonald J F, El Sayed M A. Gold nanorod assisted near-infrared plasmonic photothermal therapy (PPTT) of squamous cell carcinoma in mice. Cancer Letters, 2008, 269(1): 57–66

[28] Yang K, Feng L, Shi X, Liu Z. Nano-graphene in biomedicine: theranostic applications. Chemical Society Reviews, 2013, 42(2): 530–547

[29] Guo L, Yan D D, Yang D, Li Y, Wang X, Zalewski O, Yan B, Lu W. Combinatorial photothermal and immuno cancer therapy using chitosan-coated hollow copper sulfide nanoparticles. ACS Nano, 2014, 8(6): 5670–5681

[30] Wang C, Xu L, Liang C, Xiang J, Peng R, Liu Z. Immunological responses triggered by photothermal therapy with carbon nanotubes in combination with anti-CTLA-4 therapy to inhibit cancer metastasis. Advanced Materials, 2014, 26(48): 8154–8162

[31] Tao Y, Ju E, Ren J, Qu X. Immunostimulatory oligonucleotides-loaded cationic graphene oxide with photothermally enhanced immunogenicity for photothermal/immune cancer therapy. Biomaterials, 2014, 35(37): 9963–9971

[32] Chen Q, Xu L, Liang C, Wang C, Peng R, Liu Z. Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy. Nature Communications, 2016, 7(1): 1–13

[33] Liu Y, Maccarini P, Palmer G M, Etienne W, Zhao Y, Lee C T, Ma X, Inman B A, Vo-Dinh T. Synergistic immuno photothermal nanotherapy (SYMPHONY) for the treatment of unresectable and metastatic cancers. Scientific Reports, 2017, 7(1): 8606

[34] Nam J, Son S, Ochyl L J, Kuai R, Schwendeman A, Moon J J. Chemo-photothermal therapy combination elicits anti-tumor immunity against advanced metastatic cancer. Nature Communications, 2018, 9(1): 1074

[35] Yu G T, Rao L, Wu H, Yang L L, Bu L L, Deng W W, Wu L, Nan X, Zhang W F, Zhao X Z, Liu W, Sun Z J. Myeloid-derived suppressor cell membrane-coated magnetic nanoparticles for cancer theranostics by Inducing macrophage polarization and synergizing immunogenic cell death. Advanced Functional Materials, 2018, 28(37): 1801389

[36] Dong X, Liang J, Yang A, Qian Z, Kong D, Lv F. Fluorescence imaging guided CpG nanoparticles-loaded IR820-hydrogel for synergistic photothermal immunotherapy. Biomaterials, 2019, 209: 111–125

[37] Zhang D, Wu T, Qin X, Qiao Q, Shang L, Song Q, Yang C, Zhang Z. Intracellularly generated immunological gold nanoparticles for combinatorial photothermal therapy and immunotherapy against tumor. Nano Letters, 2019, 19(9): 6635–6646

[38] Chao Y, Chen G, Liang C, Xu J, Dong Z, Han X, Wang C, Liu Z. Iron nanoparticles for low-power local magnetic hyperthermia in combination with immune checkpoint blockade for systemic antitumor therapy. Nano Letters, 2019, 19(7): 4287–4296

[39] Ong C, Cha B G, Kim J. Mesoporous silica nanoparticles doped with gold nanoparticles for combined cancer immunotherapy and photothermal therapy. ACS Applied Bio Materials, 2019, 2(8): 3630–3638

[40] Ma Y, Zhang Y, Li X, Zhao Y, Li M, Jiang W, Tang X, Dou J, Lu L, Wang F, Wang Y. Near-infrared II phototherapy induces deep tissue immunogenic cell death and potentiates cancer immunotherapy. ACS Nano, 2019, 13(10): 11967–11980

[41] Wang Z, Guo B, Middha E, Huang Z, Hu Q, Fu Z, Liu B. Microfluidics-prepared uniform conjugated polymer nanoparticles for photo-triggered immune microenvironment modulation and cancer therapy. ACS Applied Materials & Interfaces, 2019, 11(12): 11167–11176

[42] Li Y, Liu X, Pan W, Li N, Tang B. Photothermal therapy-induced immunogenic cell death based on natural melanin nanoparticles against breast cancer. Chemical Communications, 2020, 56(9): 1389–1392

[43] Bezu L, Gomes-da-Silva L C, Dewitte H, Breckpot K, Fucikova J, Spisek R, Galluzzi L, Kepp O, Kroemer G. Combinatorial strategies for the induction of immunogenic cell death. Frontiers in Immunology, 2015, 6: 187

[44] Duan X, Chan C, Lin W. Nanoparticle-mediated immunogenic cell death enables and potentiates cancer immunotherapy. Angewandte Chemie International Edition, 2019, 58(3): 670–680

[45] Rodallec A, Sicard G, Fanciullino R, Benzekry S, Lacarelle B, Milano G, Ciccolini J. Turning cold tumors into hot tumors: harnessing the potential of tumor immunity using nanoparticles. Expert Opinion on Drug Metabolism & Toxicology, 2018, 14(11): 1139–1147

[46] Wang S, Riedinger A, Li H, Fu C, Liu H, Li L, Liu T, Tan L, Barthel M J, Pugliese G, De Donato F, Scotto D’Abbusco M, Meng X, Manna L, Meng H, Pellegrino T. Plasmonic copper sulfide nanocrystals exhibiting near-infrared photothermal and photodynamic therapeutic effects. ACS Nano, 2015, 9(2): 1788–1800

[47] Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Immunogenic cell death in cancer therapy. Annual Review of Immunology, 2013, 31(1): 51–72

[48] Garg A D, Dudek-Peric A M, Romano E, Agostinis P. Immunogenic cell death. International Journal of Developmental Biology, 2015, 59(1-3): 131–140

[49] Liu X, Jiang J, Liao Y P, Tang I, Zheng E, Qiu W, Lin M, Wang X, Ji Y, Mei K C, . Combination chemo-immunotherapy for pancreatic cancer using the immunogenic effects of an irinotecan silicasome nanocarrier plus anti-PD-1. Advancement of Science, 2021, 8(6): 2002147

[50] Wong D Y, Ong W W, Ang W H. Induction of immunogenic cell death by chemotherapeutic platinum complexes. Angewandte Chemie International Edition in English, 2015, 54(22): 6483–6487

[51] Verfaillie T, Rubio N, Garg A D, Bultynck G, Rizzuto R, Decuypere J P, Piette J, Linehan C, Gupta S, Samali A, Agostinis P. PERK is required at the ER-mitochondrial contact sites to convey apoptosis after ROS-based ER stress. Cell Death and Differentiation, 2012, 19(11): 1880–1891

[52] Garg A D, Krysko D V, Verfaillie T, Kaczmarek A, Ferreira G B, Marysael T, Rubio N, Firczuk M, Mathieu C, Roebroek A J, Annaert W, Golab J, de Witte P, Vandenabeele P, Agostinis P. A novel pathway combining calreticulin exposure and ATP secretion in immunogenic cancer cell death. EMBO Journal, 2012, 31(5): 1062–1079

[53] Radogna F, Diederich M. Stress-induced cellular responses in immunogenic cell death: implications for cancer immunotherapy. Biochemical Pharmacology, 2018, 153: 12–23

[54] Krysko D V, Garg A D, Kaczmarek A, Krysko O, Agostinis P, Vandenabeele P. Immunogenic cell death and DAMPs in cancer therapy. Nature Reviews. Cancer, 2012, 12(12): 860–875

[55] Li W, Yang J, Luo L, Jiang M, Qin B, Yin H, Zhu C, Yuan X, Zhang J, Luo Z, Du Y, Li Q, Lou Y, Qiu Y, You J. Targeting photodynamic and photothermal therapy to the endoplasmic reticulum enhances immunogenic cancer cell death. Nature Communications, 2019, 10(1): 3349

[56] Dimou A, Syrigos K N, Saif M W. Overcoming the stromal barrier: technologies to optimize drug delivery in pancreatic cancer. Therapeutic Advances in Medical Oncology, 2012, 4(5): 271–279

[57] Meng H, Zhao Y, Dong J, Xue M, Lin Y S, Ji Z, Mai W X, Zhang H, Chang C H, Brinker C J, Zink J I, Nel A E. Two-wave nanotherapy to target the stroma and optimize gemcitabine delivery to a human pancreatic cancer model in mice. ACS Nano, 2013, 7(11): 10048–10065

[58] Miao L, Lin C M, Huang L. Stromal barriers and strategies for the delivery of nanomedicine to desmoplastic tumors. Journal of Controlled Release, 2015, 219: 192–204

[59] Meng H, Nel A E. Use of nano engineered approaches to overcome the stromal barrier in pancreatic cancer. Advanced Drug Delivery Reviews, 2018, 130: 50–57

[60] Rosenberg A, Mahalingam D. Immunotherapy in pancreatic adenocarcinoma-overcoming barriers to response. Journal of Gastrointestinal Oncology, 2018, 9(1): 143–159

[61] Torphy R J, Zhu Y, Schulick R D. Immunotherapy for pancreatic cancer: barriers and breakthroughs. Annals of Gastroenterological Surgery, 2018, 2(4): 274–281

[62] Issels R D. Hyperthermia adds to chemotherapy. European Journal of Cancer, 2008, 44(17): 2546–2554

[63] Nam J, Son S, Park K S, Zou W P, Shea L D, Moon J J. Cancer nanomedicine for combination cancer immunotherapy. Nature Reviews. Materials, 2019, 4(6): 398–414

[64] Peng J, Xiao Y, Li W, Yang Q, Tan L, Jia Y, Qu Y, Qian Z. Photosensitizer micelles together with IDO inhibitor enhance cancer photothermal therapy and immunotherapy. Advancement of Science, 2018, 5(5): 1700891

[65] Li Y, Li X, Zhou F, Doughty A, Hoover A R, Nordquist R E, Chen W R. Nanotechnology-based photoimmunological therapies for cancer. Cancer Letters, 2019, 442: 429–438

[66] Liu X, Zhang Y, Wang Y, Zhu W, Li G, Ma X, Zhang Y, Chen S, Tiwari S, Shi K, Zhang S, Fan H M, Zhao Y X, Liang X J. Comprehensive understanding of magnetic hyperthermia for improving antitumor therapeutic efficacy. Theranostics, 2020, 10(8): 3793–3815

[67] Mei K C, Liao Y P, Jiang J, Chiang M, Khazaieli M, Liu X, Wang X, Liu Q, Chang C H, Zhang X, Li J, Ji Y, Melano B, Telesca D, Xia T, Meng H, Nel A E. Liposomal delivery of mitoxantrone and a cholesteryl indoximod prodrug provides effective chemo-immunotherapy in multiple solid tumors. ACS Nano, 2020, 14(10): 13343–13366

[68] Stephen Z R, Zhang M. Recent progress in the synergistic combination of nanoparticle-mediated hyperthermia and immunotherapy for treatment of cancer. Advanced Healthcare Materials, 2020, 10(2): 2001415

[69] Wang S, Sun Z, Hou Y. Engineering nanoparticles toward the modulation of emerging cancer immunotherapy. Advanced Healthcare Materials, 2020, 10(5): e2000845

[70] Mortezaee K, Narmani A, Salehi M, Bagheri H, Farhood B, Haghi-Aminjan H, Najafi M. Synergic effects of nanoparticles-mediated hyperthermia in radiotherapy/chemotherapy of cancer. Life Sciences, 2021, 269: 119020

[71] Liu X S, Jiang J H, Chang C H, Liao Y P, Jared J L, Tang I, Zheng E, Qiu W, Lin M, Wang X, . Development of facile and versatile platinum drug delivering silicasome nanocarriers for efficient pancreatic cancer chemo-immunotherapy. Small, 2021, 17(14): 2005993

[72] Chen J, Lin L, Yan N, Hu Y, Fang H, Guo Z, Sun P, Tian H, Chen X. Macrophages loaded CpG and GNR-PEI for combination of tumor photothermal therapy and immunotherapy. Science China Materials, 2018, 61(11): 1484–1494

[73] Musetti S, Huang L. Nanoparticle-mediated remodeling of the tumor microenvironment to enhance immunotherapy. ACS Nano, 2018, 12(12): 11740–11755

[74] Allen S D, Liu X, Jiang J, Liao Y P, Chang C H, Nel A E, Meng H. Immune checkpoint inhibition in syngeneic mouse cancer models by a silicasome nanocarrier delivering a GSK3 inhibitor. Biomaterials, 2021, 269: 120635

[75] Chen P M, Pan W Y, Wu C Y, Yeh C Y, Korupalli C, Luo P K, Chou C J, Chia W T, Sung H W. Modulation of tumor microenvironment using a TLR-7/8 agonist-loaded nanoparticle system that exerts low-temperature hyperthermia and immunotherapy for in situ cancer vaccination. Biomaterials, 2020, 230: 119629

[76] Shobaki N, Sato Y, Suzuki Y, Okabe N, Harashima H. Manipulating the function of tumor-associated macrophages by siRNA-loaded lipid nanoparticles for cancer immunotherapy. Journal of Controlled Release, 2020, 325: 235–248

[77] Teo P Y, Yang C, Whilding L M, Parente-Pereira A C, Maher J, George A J, Hedrick J L, Yang Y Y, Ghaem-Maghami S. Ovarian cancer immunotherapy using PD-L1 siRNA targeted delivery from folic acid-functionalized polyethylenimine: strategies to enhance T cell killing. Advanced Healthcare Materials, 2015, 4(8): 1180–1189

[78] Golden E B, Apetoh L. Radiotherapy and immunogenic cell death. Seminars in Radiation Oncology, 2015, 25(1): 11–17

[79] Galluzzi L, Kepp O, Kroemer G. Immunogenic cell death in radiation therapy. OncoImmunology, 2013, 2(10): e26536

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