Supramolecular micelles as multifunctional theranostic agents for synergistic photodynamic therapy and hypoxia-activated chemotherapy
文献类型：期刊论文
| 作者 | Huang, Xiaobei6,7; Chen, Tunan1,2; Mu, Ning1,2; Lam, Hou Wang3; Sun, Chen4,5; Yue, Ludan4,5; Cheng, Qian4,5; Gao, Cheng4,5; Yuan, Zhen7; Wang, Ruibing4,5 |
| 刊名 | ACTA BIOMATERIALIA
 |
| 出版日期 | 2021-09-01 |
| 卷号 | 131页码:483-492 |
| 关键词 | Photodynamic-chemotherapeutic therapy Supramolecular Hypoxia-activated prodrug Targeted drug delivery Controlled drug release |
| ISSN号 | 1742-7061 |
| DOI | 10.1016/j.actbio.2021.07.014 |
| 通讯作者 | Yuan, Zhen(zhenyuan@umac.mo) ; Wang, Ruibing(rwang@um.edu.mo) |
| 英文摘要 | Photodynamic therapy (PDT), where a photosensitizer (under light irradiation) converts molecular oxy-gen to singlet oxygen to elicit programmed cell death, is a promising cancer treatment modality with a high temporal and spatial resolution. However, only limited cancer treatment efficacy has been achieved in clinical PDT due to the hypoxic conditions of solid tumor microenvironment that limits the gener-ation of singlet oxygen, and PDT process often leads to even more hypoxic microenvironment due to the consumption of oxygens during therapy. Herein, we designed novel supramolecular micelles to co-deliver photosensitizer and hypoxia-responsive prodrug to improve the overall therapeutic efficacy. The supramolecular micelles (CPC) were derived from a polyethylene glycol (PEG) system dually tagged with hydrophilic cucurbit[7]uril (CB[7]) and hydrophobic Chlorin e6 (Ce6), respectively on each end, for syn-ergistic antitumor therapy via PDT of Ce6 and chemotherapy of a hypoxia-responsive prodrug, banox-antrone (AQ4N), loaded into the cavity of CB[7]. In addition, CPC was further modularly functionalized by folate (FA) via strong host-guest interaction between folate-amantadine (FA-ADA) and CB[7] to produce a novel nanoplatform, AQ4N@CPC-FA, for targeted delivery. AQ4N@CPC-FA exhibited enhanced cellular up-take, negligible cytotoxicity and good biocompatibility, and improved intracellular reactive oxygen species (ROS) generation efficiency. More importantly, in vivo evaluation of AQ4N@CPC-FA revealed a synergistic antitumor efficacy between PDT of Ce6 and hypoxia-activated chemotherapy of AQ4N (that can be con-verted to chemotherapeutic AQ4 for tumor chemotherapy in response to the strengthened hypoxic tumor microenvironment during PDT treatment). This study not only provides a new nanoplatform for syner-gistic photodynamic-chemotherapeutic treatment, but also offers important new insights to design and development of multifunctional supramolecular drug delivery system. Statement of significance Photodynamic therapy (PDT) has exhibited a variety of advantages for cancer phototherapy as com-pared to traditional chemotherapy. However, the unsatisfactory therapeutic efficacy by PDT alone as a result of the enhanced tumor hypoxia during PDT has limited its clinical application. Herein, we de-signed multifunctional supramolecular micelles to co-deliver photosensitizer and hypoxia-responsive pro-drug to improve the overall therapeutic efficacy. The supramolecular micelles are biocompatible and pos-sess strong red absorption, controlled drug release profile, and ultimately enhanced therapeutic outcome via PDT-chemotherapy. This study not only provides a new nanoplatform for synergistic photodynamicchemotherapeutic treatment of cancer, but also offers im portant new insights to design and development of multifunctional supramolecular drug delivery tool for multi-modality cancer therapy. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. |
| 资助项目 | Science and Technology Development Fund, Macau SAR[SKL-QRCM(UM)-2020-2022] ; Science and Technology Development Fund, Macau SAR[0011/2018/A1] ; Science and Technology Development Fund, Macau SAR[0020/2019/AMJ] ; University of Macau[MYRG2017-00010-ICMS] ; University of Macau[MYRG2018-00081-FHS] ; University of Macau[MYRG2019-00082-FHS] ; University of Macau[MYRG 2020-00067-FHS] ; Talents Training Program of Army Medical University[2019MPRC021/SWH2018QNWQ-05] ; National Natural Science Foundation of China (NSFC)[8102067] |
| WOS研究方向 | Engineering ; Materials Science |
| 语种 | 英语 |
| WOS记录号 | WOS:000685311400004 |
| 出版者 | ELSEVIER SCI LTD |
| 源URL | [http://119.78.100.138/handle/2HOD01W0/13906]  |
| 专题 | 中国科学院重庆绿色智能技术研究院 |
| 通讯作者 | Yuan, Zhen; Wang, Ruibing |
| 作者单位 | 1.Army Mil Med Univ, Mil Med Univ 3, Southwest Hosp, Dept Neurosurg, Chongqing 400038, Peoples R China 2.Army Mil Med Univ, Mil Med Univ 3, Southwest Hosp, Key Lab Neurotrauma, Chongqing 400038, Peoples R China 3.Kings Coll London, Fac Life Sci & Med, London, England 4.Univ Macau, Inst Chinese Med Sci, MoE Frontiers Sci Ctr Precis Oncol, Taipa 999078, Macao, Peoples R China 5.Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Taipa 999078, Macao, Peoples R China 6.Chinese Acad Sci, Chongqing Inst Green & Intelligent Technol, Chongqing 400714, Peoples R China 7.Univ Macau, Fac Hlth Sci, Taipa 999078, Macao, Peoples R China |
| 推荐引用方式 GB/T 7714 | Huang, Xiaobei,Chen, Tunan,Mu, Ning,et al. Supramolecular micelles as multifunctional theranostic agents for synergistic photodynamic therapy and hypoxia-activated chemotherapy[J]. ACTA BIOMATERIALIA,2021,131:483-492. |
| APA | Huang, Xiaobei.,Chen, Tunan.,Mu, Ning.,Lam, Hou Wang.,Sun, Chen.,...&Wang, Ruibing.(2021).Supramolecular micelles as multifunctional theranostic agents for synergistic photodynamic therapy and hypoxia-activated chemotherapy.ACTA BIOMATERIALIA,131,483-492. |
| MLA | Huang, Xiaobei,et al."Supramolecular micelles as multifunctional theranostic agents for synergistic photodynamic therapy and hypoxia-activated chemotherapy".ACTA BIOMATERIALIA 131(2021):483-492. |
入库方式： OAI收割
来源：重庆绿色智能技术研究院
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