Hypoxia-responsive nanoreactors based on self-enhanced photodynamic sensitization and triggered ferroptosis for cancer synergistic therapy
Tóm tắt
Photodynamic therapy (PDT), a typical reactive oxygen species (ROS)-dependent treatment with high controllability, has emerged as an alternative cancer therapy modality but its therapeutic efficacy is still unsatisfactory due to the limited light penetration and constant oxygen consumption. With the development of another ROS-dependent paradigm ferroptosis, several efforts have been made to conquer the poor efficacy by combining these two approaches; however the biocompatibility, tumor-targeting capacity and clinical translation prospect of current studies still exist great concerns. Herein, a novel hypoxia-responsive nanoreactor BCFe@SRF with sorafenib (SRF) loaded inside, constructed by covalently connecting chlorin e6 conjugated bovine serum albumin (BSA-Ce6) and ferritin through azobenzene (Azo) linker, were prepared to offer unmatched opportunities for high-efficient PDT and ferroptosis synergistic therapy. The designed BCFe@SRF exhibited appropriate size distribution, stable dispersity, excellent ROS generation property, controllable drug release capacity, tumor accumulation ability, and outstanding biocompatibility. Importantly, the BCFe@SRF could be degraded under hypoxia environment to release BSA-Ce6 for laser-triggered PDT, ferritin for iron-catalyzed Fenton reaction and SRF for tumor antioxidative defense disruption. Meanwhile, besides PDT effects, it was found that BCFe@SRF mediated treatment upon laser irradiation in hypoxic environment not only could accelerate lipid peroxidation (LPO) generation but also could deplete intracellular glutathione (GSH) and decrease glutathione peroxidase (GPX4) expression, which was believed as three symbolic events during ferroptosis. All in all, the BCFe@SRF nanoreactor, employing multiple cascaded pathways to promote intracellular ROS accumulation, presented remarkably outstanding antitumor effects both in vitro and in vivo. BCFe@SRF could serve as a promising candidate for synergistic PDT and ferroptosis therapy, which is applicable to boost oxidative damage within tumor site and will be informative to future design of ROS-dependent therapeutic nanoplatforms.
Tài liệu tham khảo
Tang ZM, Liu YY, Ni DL, Zhou JJ, Zhang M, Zhao PR, Lv B, Wang H, Jin DY, Bu WB. Biodegradable nanoprodrugs: “delivering” ROS to cancer cells for molecular dynamic therapy. Adv Mater. 2020;32:1904011.
Jasim KA, Gesquiere AJ. Ultrastable and biofunctionalizable conjugated polymer nanoparticles with encapsulated iron for ferroptosis assisted chemodynamic therapy. Mol Pharm. 2019;16:4852–66.
Yang B, Ding L, Yao H, Chen Y, Shi J. A metal-organic framework (MOF) fenton nanoagent-enabled nanocatalytic cancer therapy in synergy with autophagy inhibition. Adv Mater. 2020;32:e1907152.
Wu M, Ding Y, Li L. Recent progress in the augmentation of reactive species with nanoplatforms for cancer therapy. Nanoscale. 2019;11:19658–83.
Wei Z, Liang P, Xie J, Song C, Tang C, Wang Y, Yin X, Cai Y, Han W, Dong X. Carrier-free nano-integrated strategy for synergetic cancer anti-angiogenic therapy and phototherapy. Chem Sci. 2019;10:2778–84.
Yang H, Liu R, Xu Y, Qian L, Dai Z. Photosensitizer nanoparticles boost photodynamic therapy for pancreatic cancer treatment. Nano-Micro Lett. 2021;13:1–16.
Ding L, Lin X, Lin Z, Wu Y, Liu X, Liu J, Wu M, Zhang X, Zeng Y. Cancer cell-targeted photosensitizer and therapeutic protein co-delivery nanoplatform based on a metal-organic framework for enhanced synergistic photodynamic and protein therapy. ACS Appl Mater Interfaces. 2020;12:36906–16.
Lin X, Wu M, Li M, Cai Z, Sun H, Tan X, Li J, Zeng Y, Liu X, Liu J. Photo-responsive hollow silica nanoparticles for light-triggered genetic and photodynamic synergistic therapy. Acta Biomater. 2018;76:178–92.
Lo PC, Rodriguez-Morgade MS, Pandey RK, Ng DKP, Torres T, Dumoulin F. The unique features and promises of phthalocyanines as advanced photosensitisers for photodynamic therapy of cancer. Chem Soc Rev. 2020;49:1041–56.
Gao J, Zhou H, Zhao Y, Lu L, Zhang J, Cheng W, Song X, Zheng Y, Chen C, Tang J. Time-course effect of ultrasmall superparamagnetic iron oxide nanoparticles on intracellular iron metabolism and ferroptosis activation. Nanotoxicology. 2021;15:366–79.
Meng X, Deng J, Liu F, Guo T, Liu M, Dai P, Fan A, Wang Z, Zhao Y. Triggered all-active metal organic framework: ferroptosis machinery contributes to the apoptotic photodynamic antitumor therapy. Nano Lett. 2019;19:7866–76.
Hu JJ, Chen Y, Li ZH, Peng SY, Sun Y, Zhang XZ. Augment of oxidative damage with enhanced photodynamic process and MTH1 inhibition for tumor therapy. Nano Lett. 2019;19:5568–76.
Tang Z, Liu Y, He M, Bu W. Chemodynamic therapy: Tumour microenvironment-mediated fenton and fenton-like reactions. Angew Chem Int Ed Engl. 2019;58:946–56.
Hwang E, Jung HS. Metal-organic complex-based chemodynamic therapy agents for cancer therapy. Chem Commun. 2020;56:8332–41.
Lin H, Chen Y, Shi J. Nanoparticle-triggered in situ catalytic chemical reactions for tumour-specific therapy. Chem Soc Rev. 2018;47:1938–58.
He Y, Hua Liu S, Yin J, Yoon J. Sonodynamic and chemodynamic therapy based on organic/organometallic sensitizers. Coord Chem Rev. 2021;429:213610.
Hao YN, Zhang WX, Gao YR, Wei YN, Shu Y, Wang JH. State-of-the-art advances of copper-based nanostructures in the enhancement of chemodynamic therapy. J Mater Chem B. 2021;9:250–66.
Wang X, Zhong X, Liu Z, Cheng L. Recent progress of chemodynamic therapy-induced combination cancer therapy. Nano Today. 2020;35:100946.
Wang W, Jin Y, Xu Z, Liu X, Bajwa SZ, Khan WS, Yu H. Stimuli-activatable nanomedicines for chemodynamic therapy of cancer. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2020;12:e1614.
Yang B, Dai Z, Zhang G, Hu Z, Yao X, Wang S, Liu Q, Zheng X. Ultrasmall ternary FePtMn nanocrystals with acidity-triggered dual-ions release and hypoxia relief for multimodal synergistic chemodynamic/photodynamic/photothermal cancer therapy. Adv Healthc Mater. 2020;9:e1901634.
Liang H, Guo J, Shi Y, Zhao G, Sun S, Sun X. Porous yolk-shell Fe/Fe3O4 nanoparticles with controlled exposure of highly active Fe(0) for cancer therapy. Biomaterials. 2021;268:120530.
Wang B, Zhang X, Wang Z, Shi D. Ferroptotic nanomaterials enhance cancer therapy via boosting Fenton-reaction. J Drug Deliv Sci Technol. 2020;59:101883.
Shen Z, Song J, Yung BC, Zhou Z, Wu A, Chen X. Emerging strategies of cancer therapy based on ferroptosis. Adv Mater. 2018;30:e1704007.
Shen Z, Liu T, Li Y, Lau J, Yang Z, Fan W, Zhou Z, Shi C, Ke C, Bregadze VI, Mandal SK, Liu Y, Li Z, Xue T, Zhu G, Munasinghe J, Niu G, Wu A, Chen X. Fenton-reaction-acceleratable magnetic nanoparticles for ferroptosis therapy of orthotopic brain tumors. ACS Nano. 2018;12:11355–65.
Jiang Q, Wang K, Zhang X, Ouyang B, Liu H, Pang Z, Yang W. Platelet membrane-camouflaged magnetic nanoparticles for ferroptosis-enhanced cancer immunotherapy. Small. 2020;16:e2001704.
Chen Q, Ma X, Xie L, Chen W, Xu Z, Song E, Zhu X, Song Y. Iron-based nanoparticles for MR imaging-guided ferroptosis in combination with photodynamic therapy to enhance cancer treatment. Nanoscale. 2021;13:4855–70.
Zhu T, Shi L, Yu C, Dong Y, Qiu F, Shen L, Qian Q, Zhou G, Zhu X. Ferroptosis promotes photodynamic therapy: supramolecular photosensitizer-inducer nanodrug for enhanced cancer treatment. Theranostics. 2019;9:3293–307.
Xu T, Ma Y, Yuan Q, Hu H, Hu X, Qian Z, Rolle JK, Gu Y, Li S. Enhanced ferroptosis by oxygen-boosted phototherapy based on a 2-in-1 nanoplatform of ferrous hemoglobin for tumor synergistic therapy. ACS Nano. 2020;14:3414–25.
Liu T, Liu W, Zhang M, Yu W, Gao F, Li C, Wang SB, Feng J, Zhang XZ. Ferrous-supply-regeneration nanoengineering for cancer-cell-specific ferroptosis in combination with imaging-guided photodynamic therapy. ACS Nano. 2018;12:12181–92.
Cheng YJ, Hu JJ, Qin SY, Zhang AQ, Zhang XZ. Recent advances in functional mesoporous silica-based nanoplatforms for combinational photo-chemotherapy of cancer. Biomaterials. 2020;232:119738.
Lin X, Wang X, Gu Q, Lei D, Liu X, Yao C. Emerging nanotechnological strategies to reshape tumor microenvironment for enhanced therapeutic outcomes of cancer immunotherapy. Biomed Mater. 2021;16:042001.
Wang X, Xuan Z, Zhu X, Sun H, Li J, Xie Z. Near-infrared photoresponsive drug delivery nanosystems for cancer photo-chemotherapy. J Nanobiotechnol. 2020;18:108.
Zhao P, Tang Z, Chen X, He Z, He X, Zhang M, Liu Y, Ren D, Zhao K, Bu W. Ferrous-cysteine–phosphotungstate nanoagent with neutral pH fenton reaction activity for enhanced cancer chemodynamic therapy. Mater Horiz. 2019;6:369–74.
Biswas C, Zhang Y, DeCastro R, Guo H, Nakamura T, Kataoka H, Nabeshima K. The human tumor cell-derived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily. Cancer Res. 1995;55:434–9.
Roomi MW, Monterrey JC, Kalinovsky T, Rath M, Niedzwiecki A. Distinct patterns of matrix metalloproteinase-2 and -9 expression in normal human cell lines. Oncol Rep. 2009;21:821–6.
Lee EJ, Lee NK, Kim IS. Bioengineered protein-based nanocage for drug delivery. Adv Drug Deliv Rev. 2016;106:157–71.
Lohcharoenkal W, Wang L, Chen YC, Rojanasakul Y. Protein nanoparticles as drug delivery carriers for cancer therapy. Biomed Res Int. 2014;2014:180549.
Sandra F, Khaliq NU, Sunna A, Care A. Developing protein-based nanoparticles as versatile delivery systems for cancer therapy and imaging. Nanomaterials. 2019;9:1329.
Gaber M, Medhat W, Hany M, Saher N, Fang JY, Elzoghby A. Protein-lipid nanohybrids as emerging platforms for drug and gene delivery: Challenges and outcomes. J Control Release. 2017;254:75–91.
Truffi M, Fiandra L, Sorrentino L, Monieri M, Corsi F, Mazzucchelli S. Ferritin nanocages: a biological platform for drug delivery, imaging and theranostics in cancer. Pharmacol Res. 2016;107:57–65.
Liang M, Fan K, Zhou M, Duan D, Zheng J, Yang D, Feng J, Yan X. H-ferritin-nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single-dose injection. Proc Natl Acad Sci. 2014;111:14900–5.
Hou W, Xie Y, Song X, Sun X, Lotze MT, Zeh HJ 3rd, Kang R, Tang D. Autophagy promotes ferroptosis by degradation of ferritin. Autophagy. 2016;12:1425–8.
Gao M, Monian P, Pan Q, Zhang W, Xiang J, Jiang X. Ferroptosis is an autophagic cell death process. Cell Res. 2016;26:1021–32.
Yang RZ, Xu WN, Zheng HL, Zheng XF, Li B, Jiang LS, Jiang SD. Involvement of oxidative stress-induced annulus fibrosus cell and nucleus pulposus cell ferroptosis in intervertebral disc degeneration pathogenesis. J Cell Physiol. 2021;236:2725–39.
Park E, Chung SW. ROS-mediated autophagy increases intracellular iron levels and ferroptosis by ferritin and transferrin receptor regulation. Cell Death Dis. 2019;10:822.
Li Y, Wang X, Yan J, Liu Y, Yang R, Pan D, Wang L, Xu Y, Li X, Yang M. Nanoparticle ferritin-bound erastin and rapamycin: a nanodrug combining autophagy and ferroptosis for anticancer therapy. Biomater Sci. 2019;7:3779–87.
Zhu YJ, Zheng B, Wang HY, Chen L. New knowledge of the mechanisms of sorafenib resistance in liver cancer. Acta Pharmacol Sin. 2017;38:614–22.
Wilhelm S, Carter C, Lynch M, Lowinger T, Dumas J, Smith RA, Schwartz B, Simantov R, Kelley S. Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov. 2006;5:835–44.
Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc J-F, De Oliveira AC, Santoro A, Raoul J-L, Forner A. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.
Li J, Meng X, Deng J, Lu D, Zhang X, Chen Y, Zhu J, Fan A, Ding D, Kong D, Wang Z, Zhao Y. Multifunctional micelles dually responsive to hypoxia and singlet oxygen: enhanced photodynamic therapy via interactively triggered photosensitizer delivery. ACS Appl Mater Interfaces. 2018;10:17117–28.
Wang W, Lin L, Ma X, Wang B, Liu S, Yan X, Li S, Tian H, Yu X. Light-induced hypoxia-triggered living nanocarriers for synergistic cancer therapy. ACS Appl Mater Interfaces. 2018;10:19398–407.
Zhang X, Wu M, Li J, Lan S, Zeng Y, Liu X, Liu J. Light-enhanced hypoxia-response of conjugated polymer nanocarrier for successive synergistic photodynamic and chemo-therapy. ACS Appl Mater Interfaces. 2018;10:21909–19.
Li Z, Wu M, Bai H, Liu X, Tang G. Light-enhanced hypoxia-responsive nanoparticles for deep tumor penetration and combined chemo-photodynamic therapy. Chem Commun. 2018;54:13127–30.
Dai Y, Xu C, Sun X, Chen X. Nanoparticle design strategies for enhanced anticancer therapy by exploiting the tumour microenvironment. Chem Soc Rev. 2017;46:3830–52.
Yang G, Phua SZF, Lim WQ, Zhang R, Feng L, Liu G, Wu H, Bindra AK, Jana D, Liu Z, Zhao Y. A hypoxia-responsive albumin-based nanosystem for deep tumor penetration and excellent therapeutic efficacy. Adv Mater. 2019;31:e1901513.
Lin X, Wang X, Li J, Cai L, Liao F, Wu M, Zheng D, Zeng Y, Zhang Z, Liu X, Wang J, Yao C. Localized NIR-II photo-immunotherapy through the combination of photothermal ablation and in situ generated interleukin-12 cytokine for efficiently eliminating primary and abscopal tumors. Nanoscale. 2021;13:1745–58.
Chen Q, Liu Z. Albumin carriers for cancer theranostics: a conventional patform with new promise. Adv Mater. 2016;28:10557–66.
Zhang N, Zhao F, Zou Q, Li Y, Ma G, Yan X. Multitriggered tumor-responsive drug delivery vehicles based on protein and polypeptide coassembly for enhanced photodynamic tumor ablation. Small. 2016;12:5936–43.
La A, Nguyen T, Tran K, Sauble E, Tu D, Gonzalez A, Kidane TZ, Soriano C, Morgan J, Doan M, Tran K, Wang CY, Knutson MD, Linder MC. Mobilization of iron from ferritin: new steps and details. Metallomics. 2018;10:154–68.
Wang J, Yuan S, Zhang Y, Wu W, Hu Y, Jiang X. The effects of poly(zwitterions)s versus poly(ethylene glycol) surface coatings on the biodistribution of protein nanoparticles. Biomater Sci. 2016;4:1351–60.