Light-assisted hierarchical intratumoral penetration and programmed antitumor therapy based on tumor microenvironment (TME)-amendatory and self-adaptive polymeric nanoclusters

Jing Yan; Qinghua Wu; Ziyin Zhao; Jianhua Wu; Huan Ye; Qiujun Liang; Zhuchao Zhou; Mengying Hou; Xudong Li; Yong Liu; Lichen Yin

doi:10.1016/j.biomaterials.2020.120166

Light-assisted hierarchical intratumoral penetration and programmed antitumor therapy based on tumor microenvironment (TME)-amendatory and self-adaptive polymeric nanoclusters

Biomaterials. 2020 Oct:255:120166. doi: 10.1016/j.biomaterials.2020.120166. Epub 2020 Jun 2.

Authors

Jing Yan¹, Qinghua Wu¹, Ziyin Zhao¹, Jianhua Wu², Huan Ye¹, Qiujun Liang¹, Zhuchao Zhou³, Mengying Hou¹, Xudong Li¹, Yong Liu⁴, Lichen Yin⁵

Affiliations

¹ Jiangsu Key Laboratory of Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science & Technology, Soochow University, Suzhou, 215123, China.
² Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, China.
³ Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, China. Electronic address: zhouzhuchao@hotmail.com.
⁴ Jiangsu Key Laboratory of Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science & Technology, Soochow University, Suzhou, 215123, China. Electronic address: liuyong1987@suda.edu.cn.
⁵ Jiangsu Key Laboratory of Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science & Technology, Soochow University, Suzhou, 215123, China. Electronic address: lcyin@suda.edu.cn.

PMID: 32544718
DOI: 10.1016/j.biomaterials.2020.120166

Abstract

The anticancer performance of nanomedicine is largely impeded by insufficient intratumoral penetration. Herein, tumor microenvironment (TME)-amendatory and self-adaptive nanoclusters (NCs) capable of cancer-associated fibroblasts (CAFs) depletion and size/charge conversion were engineered to mediate light-assisted, hierarchical intratumoral penetration. Particularly, large-sized NCs (~50 nm) were prepared via self-assembly of FAP-α-targeting peptide-modified, ¹O₂-sensitive polymers, which were further used to envelope small-sized dendrimer (~5 nm) conjugated with Ce6 and loaded with DOX (DC/D). After systemic administration, the NCs efficiently targeted CAFs and generated lethal levels of ¹O₂ upon light irradiation, which depleted CAFs and concomitantly dissociated the NCs to liberate small-sized, positively charged DC/D. Such stroma attenuation and NCs transformation collectively facilitated the delivery of DC/D into deeper regions of CAF-rich tumors, where DOX and ¹O₂ provoked synergistic anti-cancer efficacies. This study provides an effective approach to facilitate the tumor penetration of nanomedicine by concurrently and spatiotemporally reconfiguring the nano-properties and remodeling the TME.

Keywords: Cancer-associated fibroblasts (CAFs); Light-responsiveness; Photodynamic therapy (PDT); Size reduction; Stroma depletion; Tumor penetration.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Nanomedicine*
Polymers
Tumor Microenvironment*

Substances

Polymers