Oxygen-Abundant and pH/NIR Dual-Responsive Nanocarriers for Tumor Hypoxia Reduction Therapy

Jiafeng Zhuang; Wei Zhang; Qize Xuan; Tonghao Ma; Qi Zhang; Chao Chen; Ping Wang

doi:10.1021/acsanm.1c01588

Oxygen-Abundant and pH/NIR Dual-Responsive Nanocarriers for Tumor Hypoxia Reduction Therapy

Jiafeng Zhuang, Wei Zhang, Qize Xuan, Tonghao Ma, Qi Zhang, Chao Chen, Ping Wang

Bioproducts and Biosystems Engineering

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Pre-existing tumor hypoxia and oxygen consumption by photodynamic therapy (PDT) always generate an inadequate oxygen supply, which often contributes to other therapy resistance, especially for aerobic treatments such as chemotherapy. In order to overcome this problem, we synthesized a chitosan (CS)-capped pH-/NIR-dual responsive and perfluorocarbon-based oxygen self-enriching photodynamic therapy nanosystem which could codeliver oxygen, photosensitizer, and chemotherapeutic drug. Simultaneously, in vitro results revealed that DOX release was stimulated by the acidic pH value with CS as a pH-responsive layer and rising temperature caused by the photothermal effect with an 808 nm laser, which could effectively reduce the nonspecific toxicity caused by premature drug release. Furthermore, due to the higher oxygen-carrying capability of perfluorocarbon, the decreased expression of the hypoxia-inducible factor-1α (HIF-1α) of tumors, as well as the significantly intense photodynamic effect and longer singlet (1O2) lifetime of the loaded photosensitizer, the elevated cytotoxicity was improved. More importantly, both in vitro and in vivo results showed that drug-loaded nanoparticles with oxygen-abundant properties achieved a similar anticancer therapy in both normoxic and hypoxic conditions against the difficulty led by deficient oxygen, as well as a good cellular internalization. Summarily, all these results pointed out that such a pH-/NIR-dual responsive drug carrier could enhance the synergetic anticancer therapy of chemotherapy and PDT by alleviation of tumor hypoxia, which provided a tempting controllable and multifunctional therapeutic application.

Original language	English (US)
Pages (from-to)	11480-11492
Number of pages	13
Journal	ACS Applied Nano Materials
Volume	4
Issue number	11
DOIs	https://doi.org/10.1021/acsanm.1c01588
State	Published - Nov 26 2021

Bibliographical note

Funding Information:
This work was sponsored by the National Natural Science Foundation of China (No. 21908059, 41907318, and 21636003), the China Postdoctoral Science Foundation (No. 2019M651419), Shanghai Sailing Program (No. 19YF1410900), the Fundamental Research Funds for the Central Universities (No. 22221818014), the Shanghai Postdoctoral Excellence Program (No. 2018011), the Foundation of State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences (No: GZKF202031), and the Open Funding Project of the State Key Laboratory of Bioreactor Engineering. All animal experiments were conducted in accordance with Chinese legislation on the Use and Care of Research Animals (Document No. 55, 2001), and institutional guidelines for the Care and Use of Laboratory Animals established by the East China University of Science and Technology Animal Studies Committee, and this committee approved the experiments.

Publisher Copyright:
©

Keywords

pH-/NIR-dual responsive
perfluorocarbon
photodynamic therapy
self-oxygen production
tumor hypoxia

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10.1021/acsanm.1c01588

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title = "Oxygen-Abundant and pH/NIR Dual-Responsive Nanocarriers for Tumor Hypoxia Reduction Therapy",

abstract = "Pre-existing tumor hypoxia and oxygen consumption by photodynamic therapy (PDT) always generate an inadequate oxygen supply, which often contributes to other therapy resistance, especially for aerobic treatments such as chemotherapy. In order to overcome this problem, we synthesized a chitosan (CS)-capped pH-/NIR-dual responsive and perfluorocarbon-based oxygen self-enriching photodynamic therapy nanosystem which could codeliver oxygen, photosensitizer, and chemotherapeutic drug. Simultaneously, in vitro results revealed that DOX release was stimulated by the acidic pH value with CS as a pH-responsive layer and rising temperature caused by the photothermal effect with an 808 nm laser, which could effectively reduce the nonspecific toxicity caused by premature drug release. Furthermore, due to the higher oxygen-carrying capability of perfluorocarbon, the decreased expression of the hypoxia-inducible factor-1α (HIF-1α) of tumors, as well as the significantly intense photodynamic effect and longer singlet (1O2) lifetime of the loaded photosensitizer, the elevated cytotoxicity was improved. More importantly, both in vitro and in vivo results showed that drug-loaded nanoparticles with oxygen-abundant properties achieved a similar anticancer therapy in both normoxic and hypoxic conditions against the difficulty led by deficient oxygen, as well as a good cellular internalization. Summarily, all these results pointed out that such a pH-/NIR-dual responsive drug carrier could enhance the synergetic anticancer therapy of chemotherapy and PDT by alleviation of tumor hypoxia, which provided a tempting controllable and multifunctional therapeutic application.",

keywords = "pH-/NIR-dual responsive, perfluorocarbon, photodynamic therapy, self-oxygen production, tumor hypoxia",

author = "Jiafeng Zhuang and Wei Zhang and Qize Xuan and Tonghao Ma and Qi Zhang and Chao Chen and Ping Wang",

note = "Funding Information: This work was sponsored by the National Natural Science Foundation of China (No. 21908059, 41907318, and 21636003), the China Postdoctoral Science Foundation (No. 2019M651419), Shanghai Sailing Program (No. 19YF1410900), the Fundamental Research Funds for the Central Universities (No. 22221818014), the Shanghai Postdoctoral Excellence Program (No. 2018011), the Foundation of State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences (No: GZKF202031), and the Open Funding Project of the State Key Laboratory of Bioreactor Engineering. All animal experiments were conducted in accordance with Chinese legislation on the Use and Care of Research Animals (Document No. 55, 2001), and institutional guidelines for the Care and Use of Laboratory Animals established by the East China University of Science and Technology Animal Studies Committee, and this committee approved the experiments. Publisher Copyright: {\textcopyright} ",

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T1 - Oxygen-Abundant and pH/NIR Dual-Responsive Nanocarriers for Tumor Hypoxia Reduction Therapy

AU - Zhuang, Jiafeng

AU - Zhang, Wei

AU - Xuan, Qize

AU - Ma, Tonghao

AU - Zhang, Qi

AU - Chen, Chao

AU - Wang, Ping

N1 - Funding Information: This work was sponsored by the National Natural Science Foundation of China (No. 21908059, 41907318, and 21636003), the China Postdoctoral Science Foundation (No. 2019M651419), Shanghai Sailing Program (No. 19YF1410900), the Fundamental Research Funds for the Central Universities (No. 22221818014), the Shanghai Postdoctoral Excellence Program (No. 2018011), the Foundation of State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences (No: GZKF202031), and the Open Funding Project of the State Key Laboratory of Bioreactor Engineering. All animal experiments were conducted in accordance with Chinese legislation on the Use and Care of Research Animals (Document No. 55, 2001), and institutional guidelines for the Care and Use of Laboratory Animals established by the East China University of Science and Technology Animal Studies Committee, and this committee approved the experiments. Publisher Copyright: ©

PY - 2021/11/26

Y1 - 2021/11/26

N2 - Pre-existing tumor hypoxia and oxygen consumption by photodynamic therapy (PDT) always generate an inadequate oxygen supply, which often contributes to other therapy resistance, especially for aerobic treatments such as chemotherapy. In order to overcome this problem, we synthesized a chitosan (CS)-capped pH-/NIR-dual responsive and perfluorocarbon-based oxygen self-enriching photodynamic therapy nanosystem which could codeliver oxygen, photosensitizer, and chemotherapeutic drug. Simultaneously, in vitro results revealed that DOX release was stimulated by the acidic pH value with CS as a pH-responsive layer and rising temperature caused by the photothermal effect with an 808 nm laser, which could effectively reduce the nonspecific toxicity caused by premature drug release. Furthermore, due to the higher oxygen-carrying capability of perfluorocarbon, the decreased expression of the hypoxia-inducible factor-1α (HIF-1α) of tumors, as well as the significantly intense photodynamic effect and longer singlet (1O2) lifetime of the loaded photosensitizer, the elevated cytotoxicity was improved. More importantly, both in vitro and in vivo results showed that drug-loaded nanoparticles with oxygen-abundant properties achieved a similar anticancer therapy in both normoxic and hypoxic conditions against the difficulty led by deficient oxygen, as well as a good cellular internalization. Summarily, all these results pointed out that such a pH-/NIR-dual responsive drug carrier could enhance the synergetic anticancer therapy of chemotherapy and PDT by alleviation of tumor hypoxia, which provided a tempting controllable and multifunctional therapeutic application.

AB - Pre-existing tumor hypoxia and oxygen consumption by photodynamic therapy (PDT) always generate an inadequate oxygen supply, which often contributes to other therapy resistance, especially for aerobic treatments such as chemotherapy. In order to overcome this problem, we synthesized a chitosan (CS)-capped pH-/NIR-dual responsive and perfluorocarbon-based oxygen self-enriching photodynamic therapy nanosystem which could codeliver oxygen, photosensitizer, and chemotherapeutic drug. Simultaneously, in vitro results revealed that DOX release was stimulated by the acidic pH value with CS as a pH-responsive layer and rising temperature caused by the photothermal effect with an 808 nm laser, which could effectively reduce the nonspecific toxicity caused by premature drug release. Furthermore, due to the higher oxygen-carrying capability of perfluorocarbon, the decreased expression of the hypoxia-inducible factor-1α (HIF-1α) of tumors, as well as the significantly intense photodynamic effect and longer singlet (1O2) lifetime of the loaded photosensitizer, the elevated cytotoxicity was improved. More importantly, both in vitro and in vivo results showed that drug-loaded nanoparticles with oxygen-abundant properties achieved a similar anticancer therapy in both normoxic and hypoxic conditions against the difficulty led by deficient oxygen, as well as a good cellular internalization. Summarily, all these results pointed out that such a pH-/NIR-dual responsive drug carrier could enhance the synergetic anticancer therapy of chemotherapy and PDT by alleviation of tumor hypoxia, which provided a tempting controllable and multifunctional therapeutic application.

KW - pH-/NIR-dual responsive

KW - perfluorocarbon

KW - photodynamic therapy

KW - self-oxygen production

KW - tumor hypoxia

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Oxygen-Abundant and pH/NIR Dual-Responsive Nanocarriers for Tumor Hypoxia Reduction Therapy

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