Original articles
Bo Zhuang, Ting Chen, Yueqi Huang, Zhimei Xiao, Yiguang Jin. Chemo-photothermal immunotherapy for eradication of orthotopic tumors and inhibition of metastasis by intratumoral injection of polydopamine versatile hydrogels[J]. Acta Pharmaceutica Sinica B, 2022, 12(3): 1447-1459

Chemo-photothermal immunotherapy for eradication of orthotopic tumors and inhibition of metastasis by intratumoral injection of polydopamine versatile hydrogels
Bo Zhuanga,b, Ting Chena, Yueqi Huanga, Zhimei Xiaoa, Yiguang Jina
a. Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China;
b. Department of Chemical Defense, Institute of NBC Defense, Beijing 102205, China
Abstract:
Cancer remains one of the leading causes of death globally and metastasis always leads to treatment failure. Here, we develop a versatile hydrogel loading photothermal agents, chemotherapeutics, and immune-adjuvants to eradicate orthotopic tumors and inhibit metastasis by combinational therapy. Hydrogel networks were synthesized via the thiol-Michael addition of polydopamine (PDA) with thiolated hyaluronic acid. PDA acted as a cross-linking agent and endowed the hydrogel with excellent photothermal property. Meanwhile, a chemotherapeutic agent, doxorubicin (DOX), was loaded in the hydrogel via π-π stacking with PDA and an immune-adjuvant, CpG-ODN, was loaded via electrostatic interaction. The release of DOX from the hydrogel was initially slow but accelerated due to near infrared light irradiation. The hydrogels showed remarkably synergistic effect against 4T1 cancer cells and stimulated plenty of cytokines secreting from RAW264.7 cells. Moreover, the hydrogels eradicated orthotopic murine breast cancer xenografts and strongly inhibited metastasis after intratumoral injection and light irradiation. The high anticancer efficiency of this chemo-photothermal immunotherapy resulted from the strong synergistic effect of the versatile hydrogels, including the evoked host immune response. The combinational strategy of chemo-photothermal immunotherapy is promising for highly effective treatment of breast cancer.
Key words:    Breast cancer    Polydopamine    Hydrogel    Intratumoral injection    Photothermal    Chemotherapy    Immunotherapy    Metastasis   
Received: 2021-05-26     Revised: 2021-07-08
DOI: 10.1016/j.apsb.2021.09.001
Funds: This work was partially supported by the National Natural Science Foundation of China (82073791).
Corresponding author: Yiguang Jin,E-mai:jinyg@sina.com     Email:jinyg@sina.com
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Bo Zhuang
Ting Chen
Yueqi Huang
Zhimei Xiao
Yiguang Jin

References:
[1] ChembiochemFerlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Pineros M, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer 2019;144:1941-1953
[2] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;0:1-41
[3] Zugazagoitia J, Guedes C, Ponce S, Ferrer I, Molina-Pinelo S, Paz-Ares L. Current challenges in cancer treatment. Clin Ther 2016;38:1551-1566
[4] Maeda H, Khatami M. Analyses of repeated failures in cancer therapy for solid tumors: poor tumor-selective drug delivery, low therapeutic efficacy and unsustainable costs. Clin Transl Med 2018;7:11
[5] Ng CW, Li J, Pu K. Recent progresses in phototherapy-synergized cancer immunotherapy. Adv Funct Mater 2018;28:1804688
[6] Sugie T. Immunotherapy for metastatic breast cancer. Chin Clin Oncol 2018;7:28
[7] Riley RS, June CH, Langer R, Mitchell MJ. Delivery technologies for cancer immunotherapy. Nat Rev Drug Discov 2019;18:175-196
[8] Adams S, Gatti-Mays ME, Kalinsky K, Korde LA, Sharon E, Amiri-Kordestani L, et al. Current landscape of immunotherapy in breast cancer: a review. JAMA Oncol 2019;5:1205-1214
[9] Hegde PS, Chen DS. Top 10 challenges in cancer immunotherapy. Immunity 2020;52:17-35
[10] 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. Nat Commun 2016;7:13193
[11] Kim HS, Lee DY. Near-infrared-responsive cancer photothermal and photodynamic therapy using gold nanoparticles. Polymers 2018;10:961
[12] Sun X, Zhuang B, Zhang M, Jiang H, Jin Y. Intratumorally injected photothermal agent-loaded photodynamic nanocarriers for ablation of orthotopic melanoma and breast cancer. ACS Biomater Sci Eng 2019;5:724-739
[13] Nam J, Son S, Ochyl LJ, Kuai R, Schwendeman A, Moon JJ. Chemo-photothermal therapy combination elicits anti-tumor immunity against advanced metastatic cancer. Nat Commun 2018;9:1074
[14] Chen X, Zou J, Zhang K, Zhu J, Zhang Y, Zhu Z, et al. Photothermal/matrix metalloproteinase-2 dual-responsive gelatin nanoparticles for breast cancer treatment. Acta Pharm Sin B 2021;11:271-282
[15] Wang C, Sun W, Wright G, Wang AZ, Gu Z. Inflammation-triggered cancer immunotherapy by programmed delivery of CpG and anti-PD1 antibody. Adv Mater 2016;28:8912-8920
[16] Fan Y, Kuai R, Xu Y, Ochyl LJ, Irvine DJ, Moon JJ. Immunogenic cell death amplified by co-localized adjuvant delivery for cancer immunotherapy. Nano Lett 2017;17:7387-7393
[17] Jung HS, Verwilst P, Sharma A, Shin J, Sessler JL, Kim JS. Organic molecule-based photothermal agents: an expanding photothermal therapy universe. Chem Soc Rev 2018;47:2280-2297
[18] Lv S, Miao Y, Liu D, Song F. Recent development of photothermal agents (PTAs) based on small organic molecular dyes. Chembiochem 2020;21:2098-2110
[19] Xing R, Liu K, Jiao T, Zhang N, Ma K, Zhang R, et al. An injectable self-assembling collagen-gold hybrid hydrogel for combinatorial antitumor photothermal/photodynamic therapy. Adv Mater 2016;28:3669-3676
[20] Bakalova R, Zhelev Z, Aoki I, Masamoto K, Mileva M, Obata T, et al. Multimodal silica-shelled quantum dots: direct intracellular delivery, photosensitization, toxic, and microcirculation effects. Bioconjug Chem 2008;19:1135-1142
[21] Xia B, Wang B, Shi J, Zhang Y, Zhang Q, Chen Z, et al. Photothermal and biodegradable polyaniline/porous silicon hybrid nanocomposites as drug carriers for combined chemo-photothermal therapy of cancer. Acta Biomater 2017;51:197-208
[22] Cheng W, Zeng X, Chen H, Li Z, Zeng W, Mei L, et al. Versatile polydopamine platforms: Synthesis and promising applications for surface modification and advanced nanomedicine. ACS Nano 2019;13:8537-8565
[23] Zhao L, Bi D, Qi X, Guo Y, Yue F, Wang X, et al. Polydopamine-based surface modification of paclitaxel nanoparticles for osteosarcoma targeted therapy. Nanotechnology 2019;30:255101
[24] Chen R, Zhu C, Fan Y, Feng W, Wang J, Shang E, et al. Polydopamine-based multifunctional platform for combined photothermal therapy, chemotherapy, and immunotherapy in malignant tumor treatment. ACS Applied Bio Materials 2019;2:874-883
[25] Emens LA, Middleton G. The interplay of immunotherapy and chemotherapy: harnessing potential synergies. Cancer Immunol Res 2015;3:436-443
[26] Cheng Y, Weng S, Yu L, Zhu N, Yang M, Yuan Y. The role of hyperthermia in the multidisciplinary treatment of malignant tumors. Integr Cancer Ther 2019;18:1534735419876345
[27] Singh A, Jain S, Sahoo SK. Magnetic nanoparticles for amalgamation of magnetic hyperthermia and chemotherapy: An approach towards enhanced attenuation of tumor. Mater Sci Eng C Mater Biol Appl 2020;110:110695
[28] Zheng Y, Cheng Y, Chen J, Ding J, Li M, Li C, et al. Injectable hydrogel-microsphere construct with sequential degradation for locally synergistic chemotherapy. ACS Appl Mater Interfaces 2017;9:3487-3496
[29] Yu S, He C, Chen X. Injectable hydrogels as unique platforms for local chemotherapeutics-based combination antitumor therapy. Macromol Biosci 2018;18:e1800240
[30] Zhuang B, Chen T, Xiao Z, Jin Y. Drug-loaded implantable surgical cavity-adaptive hydrogels for prevention of local tumor recurrence. Int J Pharm 2020;577:119048
[31] Santhanam S, Liang J, Baid R, Ravi N. Investigating thiol-modification on hyaluronan via carbodiimide chemistry using response surface methodology. J Biomed Mater Res A 2015;103:2300-2308
[32] Pu Y, Chen Y, Nguyen T, Xu CF, Zang L, Sosic Z, et al. Application of a label-free and domain-specific free thiol method in monoclonal antibody characterization. J Chromatogr B 2019;1114-1115:93-99
[33] Xu X, Bai B, Wang H, Suo Y. A near-infrared and temperature-responsive pesticide release platform through core-shell polydopamine@ PNIPAm nanocomposites. ACS Appl Mater Interfaces 2017;9:6424-6432
[34] Li W, Liu Z, Liu C, Guan Y, Ren J, Qu X. Manganese dioxide nanozymes as responsive cytoprotective shells for individual living cell encapsulation. Angew Chem Int Ed Engl 2017;56:13661-13665
[35] Zhang M, Li M, Du L, Zeng J, Yao T, Jin Y. Paclitaxel-in-liposome-in-bacteria for inhalation treatment of primary lung cancer. Int J Pharm 2020;578:119177
[36] Burdick JA, Prestwich GD. Hyaluronic acid hydrogels for biomedical applications. Adv Mater 2011;23:H41-56
[37] He M, Sui J, Chen Y, Bian S, Cui Y, Zhou C, et al. Localized multidrug co-delivery by injectable self-crosslinking hydrogel for synergistic combinational chemotherapy. J Mater Chem B 2017;5:4852-4862
[38] Tejido-Rastrilla R, Ferraris S, Goldmann WH, Grunewald A, Detsch R, Baldi G, et al. Studies on cell compatibility, cntibacterial behavior, and zeta potential of Ag-containing polydopamine-coated bioactive glass-ceramic. Materials 2019;12:500
[39] Wang B, Qiao C, Gao X, Yang X, Li Y, Li T. Rheological properties of N-[(2-hydroxyl)-propyl-3-trimethyl ammonium] chitosan chloride. Carbohydr Polym 2017;171:50-58
[40] Zhang H, Wang X, Wang P, Liu R, Hou X, Cao W, et al. One-pot synthesis of biodegradable polydopamine-doped mesoporous silica nanocomposites (PMSNs) as pH-sensitive targeting drug nanocarriers for synergistic chemo-photothermal therapy. RSC Adv 2018;8:37433-37440
[41] Jia L, Han F, Wang H, Zhu C, Guo Q, Li J, et al. Polydopamine-assisted surface modification for orthopaedic implants. J Orthop Translat 2019;17:82-95
[42] Zhao Z, Chen C, Wu W, Wang F, Du L, Zhang X, et al. Highly efficient photothermal nanoagent achieved by harvesting energy via excited-state intramolecular motion within nanoparticles. Nat Commun 2019;10:768
[43] Zhuang WR, Wang Y, Cui PF, Xing L, Lee J, Kim D, et al. Applications of pi–pi stacking interactions in the design of drug-delivery systems. J Control Release 2019;294:311-326
[44] Zhang L, Yang P, Guo R, Sun J, Xie R, Yang W. Multifunctional mesoporous polydopamine with hydrophobic paclitaxel for photoacoustic imaging-guided chemo-photothermal synergistic therapy. Int J Nanomedicine 2019;14:8647-8663
[45] Wang Y, Xiang Y, Xin VW, Wang XW, Peng XC, Liu XQ, et al. Dendritic cell biology and its role in tumor immunotherapy. J Hematol Oncol 2020;13:107
[46] Zhang N, Song J, Liu Y, Liu M, Zhang L, Sheng D, et al. Photothermal therapy mediated by phase-transformation nanoparticles facilitates delivery of anti-PD1 antibody and synergizes with antitumor immunotherapy for melanoma. J Control Release 2019;306:15-28
[47] Beheshti A, Wage J, McDonald JT, Lamont C, Peluso M, Hahnfeldt P, et al. Tumor-host signaling interaction reveals a systemic, age-dependent splenic immune influence on tumor development. Oncotarget 2015;6:35419-35432
[48] Chen W, Qin M, Chen X, Wang Q, Zhang Z, Sun X. Combining photothermal therapy and immunotherapy against melanoma by polydopamine-coated Al2O3 nanoparticles. Theranostics 2018;8:2229-2241
[49] Yang W, Zhang F, Deng H, Lin L, Wang S, Kang F, et al. Smart nanovesicle-mediated immunogenic cell death through tumor microenvironment modulation for effective photodynamic immunotherapy. ACS Nano 2020;14:620-631
[50] Jaime-Sanchez P, Uranga-Murillo I, Aguilo N, Khouili SC, Arias MA, Sancho D, et al. Cell death induced by cytotoxic CD8+ T cells is immunogenic and primes caspase-3-dependent spread immunity against endogenous tumor antigens. J Immunother Cancer 2020;8:e000528
[51] Wang R, He Z, Cai P, Zhao Y, Gao L, Yang W, et al. Surface-functionalized modified copper sulfide nanoparticles enhance checkpoint blockade tumor immunotherapy by photothermal therapy and antigen capturing. ACS Appl Mater Interfaces 2019;11:13964-13972
[52] Ge R, Liu C, Zhang X, Wang W, Li B, Liu J, et al. Photothermal-activatable Fe3O4 superparticle nanodrug carriers with PD-L1 immune checkpoint blockade for anti-metastatic cancer immunotherapy. ACS Appl Mater Interfaces 2018;10:20342-20355
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