A red blood cell‐derived bionic microrobot capable of hierarchically adapting to five critical stages in systemic drug delivery

Author:

Zhu Ya‐Xuan12,Jia Hao‐Ran13,Jiang Yao‐Wen1,Guo Yuxin1,Duan Qiu‐Yi1,Xu Ke‐Fei1,Shan Bai‐Hui1,Liu Xiaoyang1,Chen Xiaokai4,Wu Fu‐Gen1ORCID

Affiliation:

1. State Key Laboratory of Digital Medical Engineering Jiangsu Key Laboratory for Biomaterials and Devices School of Biological Science and Medical Engineering Southeast University Nanjing Jiangsu People's Republic of China

2. Shanghai Tenth People's Hospital Shanghai Frontiers Science Center of Nanocatalytic Medicine School of Medicine Tongji University Shanghai People's Republic of China

3. The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) Hangzhou Institute of Medicine (HIM) Chinese Academy of Sciences Hangzhou Zhejiang People's Republic of China

4. School of Chemistry Chemical Engineering and Biotechnology Nanyang Technological University Singapore Singapore

Abstract

AbstractThe tumour‐targeting efficiency of systemically delivered chemodrugs largely dictates the therapeutic outcome of anticancer treatment. Major challenges lie in the complexity of diverse biological barriers that drug delivery systems must hierarchically overcome to reach their cellular/subcellular targets. Herein, an “all‐in‐one” red blood cell (RBC)‐derived microrobot that can hierarchically adapt to five critical stages during systemic drug delivery, that is, circulation, accumulation, release, extravasation, and penetration, is developed. The microrobots behave like natural RBCs in blood circulation, due to their almost identical surface properties, but can be magnetically manipulated to accumulate at regions of interest such as tumours. Next, the microrobots are “immolated” under laser irradiation to release their therapeutic cargoes and, by generating heat, to enhance drug extravasation through vascular barriers. As a coloaded agent, pirfenidone (PFD) can inhibit the formation of extracellular matrix and increase the penetration depth of chemodrugs in the solid tumour. It is demonstrated that this system effectively suppresses both primary and metastatic tumours in mouse models without evident side effects, and may represent a new class of intelligent biomimicking robots for biomedical applications.

Funder

Natural Science Foundation of Jiangsu Province

National Natural Science Foundation of China

Fundamental Research Funds for the Central Universities

Publisher

Wiley

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