Reducing thermal damage to adjacent normal tissue with dual thermo-responsive polymer via thermo-induced phase transition for precise photothermal theranosis

文献类型： 外文期刊

第一作者： Wang, Rui

作者： Wang, Rui;Mu, Xueluer;Feng, Wenbi;Zhou, Xianfeng;Wang, Xu;Lu, Yingxi;Yu, Weisong

作者机构：

关键词： Thermo -responsive polymer; Heat transfer; Phase transition; Photothermal therapy (PTT); Chemotherapy

期刊名称：ACTA BIOMATERIALIA （ 影响因子：10.633； 五年影响因子：10.227 ）

ISSN： 1742-7061

年卷期： 2022 年 148 卷

页码：

收录情况： SCI

摘要： Photothermal therapy has been extensively studied to improve the light-to-heat efficiency for tumor ab-lation, but could cause severe damage to adjacent healthy tissue due to the thermal transfer, the random distribution of photothermal agents (PTAs), or combination hereof. Herein, we solve this dilemma with a material design strategy to develop a P(AAm-co -AN)- b-P(NIPAM-co-DMAa)-b-P(AAm-co-AN) ABA triblock copolymer by RAFT polymerization, which exhibits both UCST and LCST dual thermo-responsive behav-iors in aqueous solution. The P(AAm-co-AN) block with appropriate AN content allows to finely tune its UCST to -43 degrees C, which can effectively co-assemble with camptothecin (CPT) and Cy7-TCF, a near -infrared (NIR) PTA, realizing the photo-activated "on-demand" release of CPT and Cy7-TCF. The LCST of P(NIPAM-co-DMAa) segment is adjusted to -53 degrees C by varying DMAa content, enabling an irreversible sol-to-gel transition. The heat transfer in hydrogel and heat dissipation at the interface of hydrogel-adjacent tissue are limited, resulting in selectively cell killing in tumor, with little hyperthermia in adjacent tis-sues. Moreover, the hydrogel continues to release CPT to enhance the synergistic efficacy of PTT with chemotherapy. These results suggest that dual thermo-responsive polymer can contribute PTT with high selectivity and negligible side effects for precise medicine. Statement of Significance Photothermal therapy exploits the susceptibility of tumor cells toward external light-induced hyperther-mia, but can cause severe damage to adjacent healthy tissue due to thermal transfer, random distri-bution of photothermal agents (PTAs), or combination hereof. Here, we solve this dilemma by devel-oping a P(AAm-co -AN)- b-P(NIPAM-co-DMAa)-b-P(AAm-co-AN) triblock copolymer with UCST and LCST dual thermo-responsive behaviors, realizing the sequential micelle-unimer-hydrogel phase transitions. The polymer can effectively encapsulate PTA/drug, achieve long systemic circulation, accumulate in tumor through EPR effect, regulate drug release by controlling tumor temperature above UCST via irradiation, and finally exhibit a sol-gel transition, eradicating the heat transfer to adjacent tissue. This represents a practicable strategy to guide the design of next-generation polymeric vector that can contribute PTT with negligible side effects. (c) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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