KMS Chongqing Institute of Green and Intelligent Technology, CAS
| Supramolecular micelles as multifunctional theranostic agents for synergistic photodynamic therapy and hypoxia-activated chemotherapy | |
Huang, Xiaobei1,2; Chen, Tunan3,4; Mu, Ning3,4; Lam, Hou Wang5; Sun, Chen6,7; Yue, Ludan6,7; Cheng, Qian6,7; Gao, Cheng6,7; Yuan, Zhen2 ; Wang, Ruibing6,7
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| 2021-09-01 | |
| 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. |
| 关键词 | Photodynamic-chemotherapeutic therapy Supramolecular Hypoxia-activated prodrug Targeted drug delivery Controlled drug release |
| DOI | 10.1016/j.actbio.2021.07.014 |
| 发表期刊 | ACTA BIOMATERIALIA
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| ISSN | 1742-7061 |
| 卷号 | 131页码:483-492 |
| 通讯作者 | Yuan, Zhen(zhenyuan@umac.mo) ; Wang, Ruibing(rwang@um.edu.mo) |
| 收录类别 | SCI |
| WOS记录号 | WOS:000685311400004 |
| 语种 | 英语 |
