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Gas therapy (GT) exhibits great potential for clinical application due to its high therapeutic efficiency, low systemic side effects, and biosafety, thereinto, a multifunctional nanoplatform is generally needed for controllable gas release and precise delivery to tumor tissue. In this review, the recent development of multifunctional nanoplatforms for efficient tumor delivery of stimuli-responsive gas-releasing molecules (GRMs), which could be triggered by either exogenous physical or endogenous tumor microenvironment (TME) is summarized. The reported therapeutic gas molecules, including oxygen (O2), hydrogen sulfide (H2S), nitric oxide (NO), hydrogen (H2), and carbon monoxide (CO), etc., could directly influence or change the pathological status. Additionally, abundant nanocarriers have been employed for gas delivery into cancer region, such as mesoporous silica nanoparticles (MSNs), metal-organic frameworks (MOFs), two-dimensional (2D) nanomaterials, and liposomes, as well as non-nanocarriers including inorganic and organic nanoparticles. In the end, the outlooks of current challenges of GT and GRMs delivery nanoplatforms as well as the prospects of future clinical applications are proposed.


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Recent deveolpment of multifunctional responsive gas-releasing nanoplatforms for tumor therapeutic application

Show Author's information Zebin Yang1,2Hangrong Chen1,3( )
State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China
School of Chemical Science and Engineering, Tongji University, Shanghai 200092, China
School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China

Abstract

Gas therapy (GT) exhibits great potential for clinical application due to its high therapeutic efficiency, low systemic side effects, and biosafety, thereinto, a multifunctional nanoplatform is generally needed for controllable gas release and precise delivery to tumor tissue. In this review, the recent development of multifunctional nanoplatforms for efficient tumor delivery of stimuli-responsive gas-releasing molecules (GRMs), which could be triggered by either exogenous physical or endogenous tumor microenvironment (TME) is summarized. The reported therapeutic gas molecules, including oxygen (O2), hydrogen sulfide (H2S), nitric oxide (NO), hydrogen (H2), and carbon monoxide (CO), etc., could directly influence or change the pathological status. Additionally, abundant nanocarriers have been employed for gas delivery into cancer region, such as mesoporous silica nanoparticles (MSNs), metal-organic frameworks (MOFs), two-dimensional (2D) nanomaterials, and liposomes, as well as non-nanocarriers including inorganic and organic nanoparticles. In the end, the outlooks of current challenges of GT and GRMs delivery nanoplatforms as well as the prospects of future clinical applications are proposed.

Keywords: stimuli-responsive, gas therapy (GT), gas-releasing molecules (GRMs), exogenous, endogenous, nanoplatform

References(122)

[1]

Chen, L. C.; Zhou, S. F.; Su, L. C.; Song, J. B. Gas-mediated cancer bioimaging and therapy. ACS Nano 2019, 13, 10887–10917.

[2]

Jia, L. F.; Zhang, W. C.; Wang, C. Y. BMI1 inhibition eliminates residual cancer stem cells after PD1 blockade and activates antitumor immunity to prevent metastasis and relapse. Cell Stem Cell 2020, 27, 238–253.

[3]

Shannon, A. M.; Bouchier-Hayes, D. J.; Condron, C. M.; Toomey, D. Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies. Cancer Treat. Rev. 2003, 29, 297–307.

[4]

Xavierselvan, M.; Cook, J.; Duong, J.; Diaz, N.; Homan, K.; Mallidi, S. Photoacoustic nanodroplets for oxygen enhanced photodynamic therapy of cancer. Photoacoustics 2022, 25, 100306.

[5]

Markman, J. L.; Rekechenetskiy, A.; Holler, E.; Ljubimova, J. Y. Nanomedicine therapeutic approaches to overcome cancer drug resistance. Adv. Drug Deliver. Rev. 2013, 65, 1866–1879.

[6]

He, Q. J. Precision gas therapy using intelligent nanomedicine. Biomater. Sci. 2017, 5, 2226–2230.

[7]

Szabó, C. Hydrogen sulphide and its therapeutic potential. Nat. Rev. Drug Discov. 2007, 6, 917–935.

[8]

Szabó, C. Gasotransmitters in cancer: From pathophysiology to experimental therapy. Nat. Rev. Drug Discov. 2016, 15, 185–203.

[9]

Motterlini, R.; Otterbein, L. E. The therapeutic potential of carbon monoxide. Nat. Rev. Drug Discov. 2010, 9, 728–743.

[10]

Wegiel, B.; Gallo, D.; Csizmadia, E.; Harris, C.; Belcher, J.; Vercellotti, G. M.; Penacho, N.; Seth, P.; Sukhatme, V.; Ahmed, A. et al. Carbon monoxide expedites metabolic exhaustion to inhibit tumor growth. Cancer Res. 2013, 73, 7009–7021.

[11]

Moncada, S.; Erusalimsky, J. D. Does nitric oxide modulate mitochondrial energy generation and apoptosis? Nat Rev. Mol. Cell Biol. 2002, 3, 214–220.

[12]

Wong, C. C. L.; Gilkes, D. M.; Zhang, H. F.; Chen, J.; Wei, H.; Chaturvedi, P.; Fraley, S. I.; Wong, C. M.; Khoo, U. S.; Ng, I. O. L. et al. Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation. Proc. Natl. Acad. Sci. USA 2011, 108, 16369–16374.

[13]

Song, G. S.; Cheng, L.; Chao, Y.; Yang, K.; Liu, Z. Emerging nanotechnology and advanced materials for cancer radiation therapy. Adv. Mater. 2017, 29, 1700996.

[14]

Wang, Y. S.; Yang, T.; He, Q. J. Strategies for engineering advanced nanomedicines for gas therapy of cancer. Natl. Sci. Rev. 2020, 7, 1485–1512.

[15]

Powell, C. R.; Dillon, K. M.; Matson, J. B. A review of hydrogen sulfide (H2S) donors: Chemistry and potential therapeutic applications. Biochem. Pharmacol. 2018, 149, 110–123.

[16]

Ji, X. Y.; Wang, B. H. Strategies toward organic carbon monoxide prodrugs. Acc. Chem. Res. 2018, 51, 1377–1385.

[17]

Brown, J. M.; Wilson, W. R. Exploiting tumour hypoxia in cancer treatment. Nat. Rev. Cancer 2004, 4, 437–447.

[18]

Chen, Q.; Liang, C.; Sun, X. Q.; Chen, J. W.; Yang, Z. J.; Zhao, H.; Feng, L. Z.; Liu, Z. H2O2-responsive liposomal nanoprobe for photoacoustic inflammation imaging and tumor theranostics via in vivo chromogenic assay. Proc. Natl. Acad. Sci. USA. 2017, 114, 5343–5348.

[19]

Maman, S.; Witz, I. P. A history of exploring cancer in context. Nat. Rev. Cancer 2018, 18, 359–376.

[20]

Zhao, Y. J.; Ouyang, X. M.; Peng, Y. J.; Peng, S. J. Stimuli responsive nitric oxide-based nanomedicine for synergistic therapy. Pharmaceutics 2021, 13, 1917.

[21]

Yu, L. D.; Hu, P.; Chen, Y. Gas-generating nanoplatforms: Material chemistry, multifunctionality, and gas therapy. Adv. Mater. 2018, 30, 1801964.

[22]

Wu, X. Q.; Cheng, Y.; Zheng, R. X.; Xu, K. Q.; Yan, J.; Song, P. P.; Wang, Y. J.; Rauf, A.; Pan, Y.; Zhang, H. Y. Immunomodulation of tumor microenvironment by arginine-loaded iron oxide nanoparticles for gaseous immunotherapy. ACS Appl. Mater. Interfaces 2021, 13, 19825–19835.

[23]

Yang, Z. B.; Luo, Y.; Hu, Y. A.; Liang, K. C.; He, G.; Chen, Q.; Wang, Q. G.; Chen, H. R. Photothermo-promoted nanocatalysis combined with H2S-mediated respiration inhibition for efficient cancer therapy. Adv. Funct. Mater. 2021, 31, 2007991.

[24]

Kresge, C. T.; Leonowicz, M. E.; Roth, W. J.; Vartuli, J. C.; Beck, J. S. Ordered mesoporous molecular sieves synthesized by a liquid-crystal template mechanism. Nature 1992, 359, 710–712.

[25]

Manzano, M.; Vallet-Regí, M. Mesoporous silica nanoparticles for drug delivery. Adv. Funct. Mater. 2020, 30, 1902634.

[26]

Yang, B. W.; Chen, Y.; Shi, J. L. Mesoporous silica/organosilica nanoparticles: Synthesis, biological effect and biomedical application. Mater. Sci. Eng. R Rep. 2019, 137, 66–105.

[27]

Davis, M. E. Ordered porous materials for emerging applications. Nature 2002, 417, 813–821.

[28]

Wang, P. G.; Xian, M.; Tang, X. P.; Wu, X. J.; Wen, Z.; Cai, T. W.; Janczuk, A. J. Nitric oxide donors:  Chemical activities and biological applications. Chem. Rev. 2002, 102, 1091–1134.

[29]

G, U. R.; Axthelm, J.; Hoffmann, P.; Taye, N.; Gläser, S.; Görls, H.; Hopkins, S. L.; Plass, W.; Neugebauer, U.; Bonnet, S. et al. Co-registered molecular logic gate with a CO-releasing molecule triggered by light and peroxide. J. Am. Chem. Soc. 2017, 139, 4991–4994.

[30]

Rimmer, R. D.; Pierri, A. E.; Ford, P. C. Photochemically activated carbon monoxide release for biological targets. Toward developing air-stable photoCORMs labilized by visible light. Coordin. Chem. Rev. 2012, 256, 1509–1519.

[31]

Hong, G. S.; Lee, J. C.; Robinson, J. T.; Raaz, U.; Xie, L. M.; Huang, N. F.; Cooke, J. P.; Dai, H. J. Multifunctional in vivo vascular imaging using near-infrared II fluorescence. Nat. Med. 2012, 18, 1841–1846.

[32]

Tsai, M. F.; Chang, S. H. G.; Cheng, F. Y.; Shanmugam, V.; Cheng, Y. S.; Su, C. H.; Yeh, C. S. Au nanorod design as light-absorber in the first and second biological near-infrared windows for in vivo photothermal therapy. ACS Nano 2013, 7, 5330–5342.

[33]

Guo, R. R.; Tian, Y.; Wang, Y. J.; Yang, W. L. Near-infrared laser-triggered nitric oxide nanogenerators for the reversal of multidrug resistance in cancer. Adv. Funct. Mater. 2017, 27, 1606398.

[34]

Zhang, X.; Tian, G.; Yin, W. Y.; Wang, L. M.; Zheng, X. P.; Yan, L.; Li, J. X.; Su, H. R.; Chen, C. Y.; Gu, Z. J. et al. Controllable generation of nitric oxide by near-infrared-sensitized upconversion nanoparticles for tumor therapy. Adv. Funct. Mater. 2015, 25, 3049–3056.

[35]

Marin, A.; Muniruzzaman, M.; Rapoport, N. Mechanism of the ultrasonic activation of micellar drug delivery. J. Control. Release 2001, 75, 69–81.

[36]

Chen, J.; Luo, H. L.; Liu, Y.; Zhang, W.; Li, H. X.; Luo, T.; Zhang, K.; Zhao, Y. X.; Liu, J. J. Oxygen-self-produced nanoplatform for relieving hypoxia and breaking resistance to sonodynamic treatment of pancreatic cancer. ACS Nano 2017, 11, 12849–12862.

[37]

Jin, Z. K.; Wen, Y. Y.; Hu, Y. X.; Chen, W. W.; Zheng, X. F.; Guo, W. S.; Wang, T. F.; Qian, Z. Y.; Su, B. L.; He, Q. J. MRI-guided and ultrasound-triggered release of NO by advanced nanomedicine. Nanoscale 2017, 9, 3637–3645.

[38]

Zhang, K.; Xu, H. X.; Jia, X. Q.; Chen, Y.; Ma, M.; Sun, L. P.; Chen, H. R. Ultrasound-triggered nitric oxide release platform based on energy transformation for targeted inhibition of pancreatic tumor. ACS Nano 2016, 10, 10816–10828.

[39]

Cao, W.; Gu, Y. W.; Meineck, M.; Xu, H. P. The combination of chemotherapy and radiotherapy towards more efficient drug delivery. Chem. Asian J. 2014, 9, 48–57.

[40]

Fan, W. P.; Bu, W. B.; Zhang, Z.; Shen, B.; Zhang, H.; He, Q. J.; Ni, D. L.; Cui, Z. W.; Zhao, K. L.; Bu, J. W. et al. X-ray radiation-controlled no-release for ON-demand depth-independent hypoxic radiosensitization. Angew. Chem., Int. Ed. 2015, 54, 14026–14030.

[41]

Juzenas, P.; Chen, W.; Sun, Y. P.; Coelho, M. A. N.; Generalov, R.; Generalov, N.; Christensen, I. L. Quantum dots and nanoparticles for photodynamic and radiation therapies of cancer. Adv. Drug Deliver. Rev. 2008, 60, 1600–1614.

[42]

Ma, N.; Xu, H. P.; An, L. P.; Li, J.; Sun, Z. W.; Zhang, X. Radiation-sensitive diselenide block co-polymer micellar aggregates: Toward the combination of radiotherapy and chemotherapy. Langmuir 2011, 27, 5874–5878.

[43]

Shao, D.; Zhang, F.; Chen, F. M.; Zheng, X.; Hu, H. Z.; Yang, C.; Tu, Z. X.; Wang, Z.; Chang, Z. M.; Lu, J. N. et al. Biomimetic diselenide-bridged mesoporous organosilica nanoparticles as an X-ray-responsive biodegradable carrier for chemo-immunotherapy. Adv. Mater 2020, 32, 2004385.

[44]

Dou, Y.; Liu, Y. J.; Zhao, F. S.; Guo, Y. Y.; Li, X.; Wu, M. L.; Chang, J.; Yu, C. S. Radiation-responsive scintillating nanotheranostics for reduced hypoxic radioresistance under ROS/NO-mediated tumor microenvironment regulation. Theranostics 2018, 8, 5870–5889.

[45]

Liu, T. Z.; Zhang, N.; Wang, Z. G.; Wu, M. Y.; Chen, Y.; Ma, M.; Chen, H. R.; Shi, J. L. Endogenous catalytic generation of O2 bubbles for in situ ultrasound-guided high intensity focused ultrasound ablation. ACS Nano 2017, 11, 9093–9102.

[46]

Fan, W. P.; Lu, N.; Huang, P.; Liu, Y.; Yang, Z.; Wang, S.; Yu, G. C.; Liu, Y. J.; Hu, J. K.; He, Q. J. et al. Glucose-responsive sequential generation of hydrogen peroxide and nitric oxide for synergistic cancer starving-like/gas therapy. Angew. Chem. 2017, 129, 1249–1253.

[47]

Jin, Z. K.; Wen, Y. Y.; Xiong, L. W.; Yang, T.; Zhao, P. H.; Tan, L. W.; Wang, T. F.; Qian, Z. Y.; Su, B. L.; He, Q. J. Intratumoral H2O2-triggered release of CO from a metal carbonyl-based nanomedicine for efficient CO therapy. Chem. Commun. 2017, 53, 5557–5560.

[48]

Laurent, S.; Forge, D.; Port, M.; Roch, A.; Robic, C.; Elst, L. V.; Muller, R. N. Magnetic iron oxide nanoparticles: Synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. Chem. Rev. 2010, 110, 2574.

[49]

Liu, J. A.; Bu, W. B.; Pan, L. M.; Shi, J. L. NIR-triggered anticancer drug delivery by upconverting nanoparticles with integrated azobenzene-modified mesoporous silica. Angew. Chem., Int. Ed. 2013, 52, 4375–4379.

[50]

Thomas, C. R.; Ferris, D. P.; Lee, J. H.; Choi, E.; Cho, M. H.; Kim, E. S.; Stoddart, J. F.; Shin, J. S.; Cheon, J.; Zink, J. I. Noninvasive remote-controlled release of drug molecules in vitro using magnetic actuation of mechanized nanoparticles. J. Am. Chem. Soc. 2010, 132, 10623–10625.

[51]

Choi, H. W.; Kim, J.; Kim, J.; Kim, Y.; Song, H. B.; Kim, J. H.; Kim, K.; Kim, W. J. Light-induced acid generation on a gatekeeper for smart nitric oxide delivery. ACS Nano 2016, 10, 4199–4208.

[52]

Zhao, B.; Zhao, P. H.; Jin, Z. K.; Fan, M. J.; Meng, J.; He, Q. J. Programmed ROS/CO-releasing nanomedicine for synergetic chemodynamic-gas therapy of cancer. J. Nanobiotechnol. 2019, 17, 75.

[53]

Yang, T.; Jin, Z. K.; Wang, Z. H.; Zhao, P. H.; Zhao, B.; Fan, M. J.; Chen, L. H.; Wang, T. F; Su, B. L.; He, Q. J. Intratumoral high-payload delivery and acid-responsive release of H2 for efficient cancer therapy using the ammonia borane-loaded mesoporous silica nanomedicine. Appl. Mater. Today 2018, 11, 136–143.

[54]

Yaghi, O. M.; Li, H. L. Hydrothermal synthesis of a metal-organic framework containing large rectangular channels. J. Am. Chem. Soc. 1995, 117, 10401–10402.

[55]

Yaghi, O. M.; Li, G. M.; Li, H. L. Selective binding and removal of guests in a microporous metal-organic framework. Nature 1995, 378, 703–706.

[56]

Jiao, L.; Wang, Y.; Jiang, H. L.; Xu, Q. Metal-organic frameworks as platforms for catalytic applications. Adv. Mater 2018, 30, 1703663.

[57]

Zhao, X.; Wang, Y. X.; Li, D. S.; Bu, X. H.; Feng, P. Y. Metal-organic frameworks for separation. Adv. Mater 2018, 30, 1705189.

[58]

Yang, J.; Yang, Y. W. Metal-organic frameworks for biomedical applications. Small 2020, 16, 1906846.

[59]

Chen, J. J.; Zhu, Y. F.; Kaskel, S. Porphyrin-based metal-organic frameworks for biomedical applications. Angew. Chem., Int. Ed. 2021, 60, 5010–5035.

[60]

Gao, P.; Chen, Y. Y.; Pan, W.; Li, N.; Liu, Z.; Tang, B. Antitumor agents based on metal-organic frameworks. Angew. Chem., Int. Ed. 2021, 60, 16763–16776.

[61]

Jin, D. N.; Zhang, J. A.; Huang, Y. Y.; Qin, X. R. ; Zhuang, J. Y.; Yin, W. J.; Chen, S. J.; Wang, Y.; Hua, P.; Yao, Y. Recent advances in the development of metal-organic framework-based gas-releasing nanoplatforms for synergistic cancer therapy. Dalton Trans. 2021, 50, 1189–1196.

[62]

Pinto, R. V.; Wang, S. J.; Tavares, S. R.; Pires, J.; Antunes, F.; Vimont, A.; Clet, G.; Daturi, M.; Maurin, G.; Serre, C. et al. Tuning cellular biological functions through the controlled release of NO from a porous Ti-MOF. Angew. Chem. , Int. Ed. 2020, 59, 5135–5143.

[63]

Jin, Z. K.; Zhao, P. H.; Zhang, J. H.; Yang, T.; Zhou, G. X.; Zhang, D. H.; Wang, T. F.; He, Q. J. Intelligent metal carbonyl metal-organic framework nanocomplex for fluorescent traceable H2O2-triggered CO delivery. Chem.—Eur. J. 2018, 24, 11667–11674.

[64]

Cai, W.; Wang, J. Q.; Chu, C. C.; Chen, W.; Wu, C. S.; Liu, G. Metal-organic framework-based stimuli-responsive systems for drug delivery. Adv. Sci. 2019, 6, 1801526.

[65]

Gao, S. T.; Zheng, P. L.; Li, Z. H.; Feng, X. C.; Yan, W. X.; Chen, S. Z.; Guo, W. S.; Liu, D. D.; Yang, X. J.; Wang, S. X. et al. Biomimetic O2-evolving metal-organic framework nanoplatform for highly efficient photodynamic therapy against hypoxic tumor. Biomaterials 2018, 178, 83–94.

[66]

Yao, J. Z.; Liu, Y.; Wang, J. W.; Jiang, Q.; She, D. J.; Guo, H. S.; Sun, N. R.; Pang, Z. Q.; Deng, C. H.; Yang, W. L. et al. On-demand CO release for amplification of chemotherapy by MOF functionalized magnetic carbon nanoparticles with NIR irradiation. Biomaterials 2019, 195, 51–62.

[67]

Diring, S.; Carné-Sánchez, A.; Zhang, J. C.; Ikemura, S.; Kim, C.; Inaba, H.; Kitagawa, S.; Furukawa, S. Light responsive metal-organic frameworks as controllable CO-releasing cell culture substrates. Chem. Sci. 2017, 8, 2381–2386.

[68]

An, J.; Hu, Y. G.; Li, C.; Hou, X. L.; Cheng, K.; Zhang, B.; Zhang, R. Y.; Li, D. Y.; Liu, S. J.; Liu, B. et al. A pH/ultrasound dual-response biomimetic nanoplatform for nitric oxide gas-sonodynamic combined therapy and repeated ultrasound for relieving hypoxia. Biomaterials 2020, 230, 119636.

[69]

Cheng, H.; Zhu, J. Y.; Li, S. Y.; Zeng, J. Y.; Lei, Q.; Chen, K. W.; Zhang, C.; Zhang, X. An O2 self-sufficient biomimetic nanoplatform for highly specific and efficient photodynamic therapy. Adv. Funct. Mater. 2016, 26, 7847–7860.

[70]

Feng, J.; Yu, W. Q.; Xu, Z.; Wang, F. A. An intelligent ZIF-8-gated polydopamine nanoplatform for in vivo cooperatively enhanced combination phototherapy. Chem. Sci. 2020, 11, 1649–1656.

[71]

Ren, Q.; Yu, N.; Wang, L. Y.; Wen, M.; Geng, P.; Jiang, Q.; Li, M. Q.; Chen, Z. G. Nanoarchitectonics with metal-organic frameworks and platinum nanozymes with improved oxygen evolution for enhanced sonodynamic/chemo-therapy. J. Colloid Interface Sci. 2022, 614, 147–159.

[72]

He, L. C.; Ni, Q. Q.; Mu, J.; Fan, W. P.; Liu, L.; Wang, Z. T.; Li, L.; Tang, W.; Liu, Y. J.; Cheng, Y. Y. et al. Solvent-assisted self-assembly of a metal-organic framework based biocatalyst for cascade reaction driven photodynamic therapy. J. Am. Chem. Soc. 2020, 142, 6822–6832.

[73]

Johnson, T. R.; Mann, B. E.; Clark, J. E.; Foresti, R.; Green, C. J.; Motterlini, R. Metal carbonyls: A new class of pharmaceuticals? Angew. Chem. , Int. Ed. 2003, 42, 3722–3729.

[74]

Johnson, T. R.; Mann, B. E.; Clark, J. E.; Foresti, R.; Green, C. J.; Motterlini, R. Carbonylmetallkomplexe-eine neue klasse von pharmazeutika? Angew. Chem. 2003, 115, 3850–3858.

[75]

Guan, Q.; Zhou, L. L.; Li, Y. A.; Dong, Y. B. A nanoscale metal-organic framework for combined photodynamic and starvation therapy in treating breast tumors. Chem. Commun. 2019, 55, 14898–14901.

[76]

Xie, Z. X.; Liang, S.; Cai, X. H.; Ding, B. B.; Huang, S. S.; Hou, Z. Y.; Ma, P. A.; Cheng, Z. Y.; Lin, J. O2-Cu/ZIF-8@Ce6/ZIF-8@F127 composite as a tumor microenvironment-responsive nanoplatform with enhanced photo-/chemodynamic antitumor efficacy. ACS Appl. Mater. Interfaces 2019, 11, 31671–31680.

[77]

Gao, S. T.; Jin, Y.; Ge, K.; Li, Z. H.; Liu, H. F.; Dai, X. Y.; Zhang, Y. H.; Chen, S. Z.; Liang, X. J.; Zhang, J. C. Self-supply of O2 and H2O2 by a nanocatalytic medicine to enhance combined chemo/chemodynamic therapy. Adv. Sci. 2019, 6, 1902137.

[78]

Yao, X. X.; Chen, D. Y.; Zhao, B.; Yang, B. R.; Jin, Z. K.; Fan, M. J.; Tao, G. R.; Qin, S. C.; Yang, W. L.; He, Q. J. Acid-degradable hydrogen-generating metal-organic framework for overcoming cancer resistance/metastasis and off-target side effects. Adv. Sci. 2022, 9, 2101965.

[79]

Liu, Z.; Robinson, J. T.; Sun, X. M.; Dai, H. J. PEGylated nanographene oxide for delivery of water-insoluble cancer drugs. J. Am. Chem. Soc. 2008, 130, 10876–10877.

[80]

Zhang, L. M.; Xia, J. G.; Zhao, Q. H.; Liu, L. W.; Zhang, Z. J. Functional graphene oxide as a nanocarrier for controlled loading and targeted delivery of mixed anticancer drugs. Small 2010, 6, 537–544.

[81]

Xu, J. S.; Zeng, F.; Wu, H.; Hu, C. P.; Yu, C. M.; Wu, S. Z. Preparation of a mitochondria-targeted and no-releasing nanoplatform and its enhanced pro-apoptotic effect on cancer cells. Small 2014, 10, 3750–3760.

[82]

Wei, F. M.; Kuang, S.; Rees, T. W.; Liao, X. X.; Liu, J. P.; Luo, D. Q.; Wang, J. Q.; Zhang, X. T.; Ji, L. N.; Chao, H. Ruthenium(II) complexes coordinated to graphitic carbon nitride: Oxygen self-sufficient photosensitizers which produce multiple ROS for photodynamic therapy in hypoxia. Biomaterials 2021, 276, 121064.

[83]

Jin, Z. K.; Duo, Y. H.; Li, Y.; Qiu, M.; Jiang, M. N.; Liu, Q.; Zhao, P. H.; Yang, T.; Liang, W. Y.; Zhang, H. et al. A novel NIR-responsive CO gas-releasing and hyperthermia-generating nanomedicine provides a curative approach for cancer therapy. Nano Today 2021, 38, 101197.

[84]

Chen, D. Y.; Jin, Z. K.; Zhao, B.; Wang, Y. S.; He, Q. J. MBene as a theranostic nanoplatform for photocontrolled intratumoral retention and drug release. Adv. Mater 2021, 33, 2008089.

[85]

Robinson, J. T.; Tabakman, S. M.; Liang, Y. Y.; Wang, H. L.; Casalongue, H. S.; Vinh, D.; Dai, H. J. Ultrasmall reduced graphene oxide with high near-infrared absorbance for photothermal therapy. J. Am. Chem. Soc. 2011, 133, 6825–6831.

[86]

Yang, Z. B.; Liu, J. T.; Liu, J. K.; Chen, X. L.; Yan, T. T.; Chen, Q. H. Investigation on physicochemical properties of graphene oxide/nano-hydroxyapatite composites and its biomedical applications. J. Aust. Ceram. Soc. 2021, 57, 625–633.

[87]

He, Q. J.; Kiesewetter, D. O.; Qu, Y.; Fu, X.; Fan, J.; Huang, P.; Liu, Y. J.; Zhu, G. Z.; Liu, Y.; Qian, Z. Y. et al. NIR-responsive on-demand release of CO from metal carbonyl-caged graphene oxide nanomedicine. Adv. Mater 2015, 27, 6740–6746.

[88]

Fan, J.; He, N. Y.; He, Q. J.; Liu, Y.; Ma, Y.; Fu, X.; Liu, Y. J.; Huang, P.; Chen, X. Y. A novel self-assembled sandwich nanomedicine for NIR-responsive release of NO. Nanoscale 2015, 7, 20055–20062.

[89]

Li, H. F.; Yao, Y.; Shi, H.; Lei, Y. L.; Wang, K. M.; He, X. X.; Liu, J. B. A near-infrared light-responsive nanocomposite for photothermal release of H2S and suppression of cell viability. J. Mater. Chem. B 2019, 7, 5992–5997.

[90]

Cao, L.; Wang, X.; Meziani, M. J.; Lu, F. S.; Wang, H. F.; Luo, P. G.; Lin, Y.; Harruff, B. A.; Veca, M.; Murray, D. et al. Carbon dots for multiphoton bioimaging. J. Am. Chem. Soc. 2007, 129, 11318–11319.

[91]

Yang, Z. B.; Luo, Y.; Yu, H. Z.; Liang, K. C.; Wang, M.; Wang, Q. G.; Yin, B.; Chen, H. R. Reshaping the tumor immune microenvironment based on a light-activated nanoplatform for efficient cancer therapy. Adv. Mater. 2022, 34, 2108908.

[92]

Fang, X.; Cai, S. X.; Wang, M.; Chen, Z. W.; Lu, C. H.; Yang, H. H. Photogenerated holes mediated nitric oxide production for hypoxic tumor treatment. Angew. Chem., Int. Ed. 2021, 60, 7046–7050.

[93]

Liu, X.; Liu, Y. L.; Thakor, A. S.; Kevadiya, B. D.; Cheng, J. M.; Chen, M. L.; Li, Y.; Xu, Q.; Wu, Q. H.; Wu, Y. et al. Endogenous NO-releasing carbon nanodots for tumor-specific gas therapy. Acta Biomater. 2021, 136, 485–494.

[94]

Fan, M. J.; Wen, Y. Y.; Ye, D. E.; Jin, Z. K.; Zhao, P. H.; Chen, D. Y.; Lu, X. F.; He, Q. J. Acid-responsive H2-releasing 2D MgB2 nanosheet for therapeutic synergy and side effect attenuation of gastric cancer chemotherapy. Adv. Healthcare Mater. 2019, 8, 1900157.

[95]

Bangham, A. D.; Standish, M. M.; Watkins, J. C. Diffusion of univalent ions across the lamellae of swollen phospholipids. Mol. Biol. 1965, 13, 238–252, IN26–IN27.

[96]

Long, M. M.; Lu, A. L.; Lu, M.; Weng, L. Y.; Chen, Q. P.; Zhu, L.; Chen, Z. P. Azo-inserted responsive hybrid liposomes for hypoxia-specific drug delivery. Acta Biomater. 2020, 115, 343–357.

[97]

Opoku-Damoah, Y.; Zhang, R.; Ta, H. T.; Jose, D. A.; Sakla, R.; Xu, Z. P. Lipid-encapsulated upconversion nanoparticle for near-infrared light-mediated carbon monoxide release for cancer gas therapy. Eur. J. Pharm. Biopharm. 2021, 158, 211–221.

[98]

Wu, W. W.; Yang, Y.; Liang, Z. Y.; Song, X. L.; Huang, Y. D.; Qiu, L.; Qiu, X. Z.; Yu, S. M.; Xue, W. Near infrared II laser controlled free radical releasing nanogenerator for synergistic nitric oxide and alkyl radical therapy of breast cancer. Nanoscale 2021, 13, 11169–11187.

[99]

Zhang, Z.; Yang, J. R.; Min, Q. Q.; Ling, C. J.; Maiti, D.; Xu, J. Y.; Qin, L. Q.; Yang, K. Holo-lactoferrin modified liposome for relieving tumor hypoxia and enhancing radiochemotherapy of cancer. Small 2019, 15, 1803703.

[100]

Suchyta, D. J.; Schoenfisch, M. H. Encapsulation of N-diazeniumdiolates within liposomes for enhanced nitric oxide donor stability and delivery. Mol. Pharmaceutics 2015, 12, 3569–3574.

[101]

Chen, X. H.; Jia, F.; Li, Y. Z.; Deng, Y. Y.; Huang, Y.; Liu, W. F.; Jin, Q.; Ji, J. Nitric oxide-induced stromal depletion for improved nanoparticle penetration in pancreatic cancer treatment. Biomaterials 2020, 246, 119999.

[102]

Zhang, X. B.; Li, N.; Zhang, S. W.; Sun, B. J.; Chen, Q.; He, Z. G.; Luo, C.; Sun, J. Emerging carrier-free nanosystems based on molecular self-assembly of pure drugs for cancer therapy. Med. Res. Rev. 2020, 40, 1754–1775.

[103]

Li, Y. A.; Yang, Y. L.; An, F. F.; Liu, Z.; Zhang, X. J.; Zhang, X. H. Carrier-free, functionalized pure drug nanorods as a novel cancer-targeted drug delivery platform. Nanotechnology 2013, 24, 015103.

[104]

Zhang, X.; Du, J. F.; Guo, Z.; Yu, J.; Gao, Q.; Yin, W. Y.; Zhu, S.; Gu, Z. J.; Zhao, Y. L. Efficient near infrared light triggered nitric oxide release nanocomposites for sensitizing mild photothermal therapy. Adv. Sci. 2019, 6, 1801122.

[105]

Zhao, P. H.; Jin, Z. K.; Chen, Q.; Yang, T.; Chen, D. Y.; Meng, J.; Lu, X. F.; Gu, Z.; He, Q. J. Local generation of hydrogen for enhanced photothermal therapy. Nat. Commun. 2018, 9, 4241.

[106]

Xue, Z. L.; Jiang, M. Y.; Liu, H. R.; Zeng, S. J.; Hao, J. H. Low dose soft X-ray-controlled deep-tissue long-lasting NO release of persistent luminescence nanoplatform for gas-sensitized anticancer therapy. Biomaterials 2020, 263, 120384.

[107]

Zhang, F. M.; Liu, S. K.; Zhang, N.; Kuang, Y.; Li, W. T.; Gai, S. L.; He, F.; Gulzar, A.; Yang, P. P. X-ray-triggered NO-released Bi-SNO nanoparticles: All-in-one nano-radiosensitizer with photothermal/gas therapy for enhanced radiotherapy. Nanoscale 2020, 12, 19293–19307.

[108]

Wang, Y.; Zhang, J. Y.; Lv, X. Y.; Wang, L.; Zhong, Z. H.; Yang, D. P.; Si, W. L.; Zhang, T.; Dong, X. C. Mitoxantrone as photothermal agents for ultrasound/fluorescence imaging-guided chemo-phototherapy enhanced by intratumoral H2O2-Induced CO. Biomaterials 2020, 252, 120111.

[109]

Sasakura, K.; Hanaoka, K.; Shibuya, N.; Mikami, Y.; Kimura, Y.; Komatsu, T.; Ueno, T.; Terai, T.; Kimura, H.; Nagano, T. Development of a highly selective fluorescence probe for hydrogen sulfide. J. Am. Chem. Soc. 2011, 133, 18003–18005.

[110]

Zheng, H. L.; Ma, B. X.; Shi, Y. S.; Dai, Q. X.; Li, D. S.; Ren, E.; Zhu, J.; Liu, J. M.; Chen, H.; Yin, Z. Y. et al. Tumor microenvironment-triggered MoS2@GA-Fe nanoreactor: A self-rolling enhanced chemodynamic therapy and hydrogen sulfide treatment for hepatocellular carcinoma. Chem. Eng. J. 2021, 406, 126888.

[111]

Liu, J. J.; Li, M. H; Luo, Z.; Dai, L. L.; Guo, X. M.; Cai, K. Y. Design of nanocarriers based on complex biological barriers in vivo for tumor therapy. Nano Today 2017, 15, 56–90.

[112]

Sun, P. P.; Jia, L.; Hai, J.; Li, S. Y.; Chen, F. J.; Liang, K.; Sun, S. H.; Liu, H. W.; Fu, X.; Zhu, Y. H. et al. Tumor microenvironment-“AND” near-infrared light-activated coordination polymer nanoprodrug for on-demand CO-sensitized synergistic cancer therapy. Adv. Healthcare Mater. 2021, 10, 2001728.

[113]

Huang, X. H.; Xu, F. N.; Hou, H. B.; Hou, J. W.; Wang, Y.; Zhou, S. B. Stimuli-responsive nitric oxide generator for light-triggered synergistic cancer photothermal/gas therapy. Nano Res. 2019, 12, 1361–1370.

[114]

Xu, Y.; Liu, J. W.; Liu, Z. Y.; Chen, G. G.; Li, X. M.; Ren, H. Damaging tumor vessels with an ultrasound-triggered NO release nanosystem to enhance drug accumulation and T cells infiltration. Int. J. Nanomed. 2021, 16, 2597–2613.

[115]

Chen, H.; Shi, T.; Wang, Y.; Liu, Z. Y.; Liu, F. C.; Zhang, H. Y.; Wang, X. W.; Miao, Z. Y.; Liu, B. R.; Wan, M. M. et al. Deep penetration of nanolevel drugs and micrometer-level T cells promoted by nanomotors for cancer immunochemotherapy. J. Am. Chem. Soc. 2021, 143, 12025–12037.

[116]

Deng, Y. Y.; Jia, F.; Chen, X. H.; Jin, Q.; Ji, J. ATP suppression by pH-activated mitochondria-targeted delivery of nitric oxide nanoplatform for drug resistance reversal and metastasis inhibition. Small 2020, 16, 2001747.

[117]

Zhang, J. M.; Song, H. J.; Ji, S. L.; Wang, X. M.; Huang, P. S.; Zhang, C. N.; Wang, W. W.; Kong, D. L. NO prodrug-conjugated, self-assembled, pH-responsive and galactose receptor targeted nanoparticles for co-delivery of nitric oxide and doxorubicin. Nanoscale 2018, 10, 4179–4188.

[118]

Li, J.; Xie, L. S.; Li, B.; Yin, C.; Wang, G. H.; Sang, W.; Li, W. X.; Tian, H.; Zhang, Z.; Zhang, X. J. et al. Engineering a hydrogen-sulfide-based nanomodulator to normalize hyperactive photothermal immunogenicity for combination cancer therapy. Adv. Mater 2021, 33, 2008481.

[119]

Deng, Y. Y.; Wang, Y. P.; Jia, F.; Liu, W. F.; Zhou, D. F.; Jin, Q.; Ji, J. Tailoring supramolecular prodrug nanoassemblies for reactive nitrogen species-potentiated chemotherapy of liver cancer. ACS Nano 2021, 15, 8663–8675.

[120]

Tu, J. Y.; Tu, K.; Xu, H. R.; Wang, L.; Yuan, X. L.; Qin, X. Y.; Kong, L.; Chu, Q.; Zhang, Z. P. Improving tumor hypoxia and radiotherapy resistance via in situ nitric oxide release strategy. Eur. J. Pharm. Biopharm. 2020, 150, 96–107.

[121]

Li, S.; Liao, R. R.; Sheng, X. Y.; Luo, X. J.; Zhang, X.; Wen, X. M.; Zhou, J.; Peng, K. Hydrogen gas in cancer treatment. Front. Oncol. 2019, 9, 696.

[122]

Tamura, T.; Hayashida, K.; Sano, M.; Suzuki, M.; Shibusawa, T.; Yoshizawa, J.; Kobayashi, Y.; Suzuki, T.; Ohta, S.; Morisaki, H. et al. Feasibility and safety of hydrogen gas inhalation for post-cardiac arrest syndrome- first-in-human pilot study. Circ. J. 2016, 80, 1870–1873.

Publication history
Copyright
Acknowledgements

Publication history

Received: 25 March 2022
Revised: 23 April 2022
Accepted: 25 April 2022
Published: 28 May 2022
Issue date: March 2023

Copyright

© Tsinghua University Press 2022

Acknowledgements

This work was supported by the National Key R&D Program of China (No. 2021YFB3801001), the National Natural Science Foundation of China (Nos. 32030061 and 81720108023), and the Key Program for Basic Research of Shanghai (Nos. 19JC1415600 and 21JC1406000).

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