Biodegradable zwitterionic polymer membrane coating endowing nanoparticles with ultra-long circulation and enhanced tumor photothermal therapy

Shaojun Peng; Boshu Ouyang; Yongzhi Men; Yang Du; Yongbin Cao; Ruihong Xie; Zhiqing Pang; Shun Shen; Wuli Yang

doi:10.1016/j.biomaterials.2019.119680

Biodegradable zwitterionic polymer membrane coating endowing nanoparticles with ultra-long circulation and enhanced tumor photothermal therapy

Biomaterials. 2020 Feb:231:119680. doi: 10.1016/j.biomaterials.2019.119680. Epub 2019 Dec 13.

Authors

Shaojun Peng¹, Boshu Ouyang², Yongzhi Men³, Yang Du², Yongbin Cao¹, Ruihong Xie¹, Zhiqing Pang⁴, Shun Shen⁵, Wuli Yang⁶

Affiliations

¹ State Key Laboratory of Molecular Engineering of Polymers & Department of Macromolecular Science, Fudan University, Shanghai, 200433, PR China.
² The Institute for Translational Nanomedicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, PR China; Central Laboratory, First Affiliated Hospital, Dalian Medical University, Dalian, 116021, PR China.
³ Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China.
⁴ Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, PR China. Electronic address: zqpang@fudan.edu.cn.
⁵ The Institute for Translational Nanomedicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, PR China. Electronic address: sshen@tongji.edu.cn.
⁶ State Key Laboratory of Molecular Engineering of Polymers & Department of Macromolecular Science, Fudan University, Shanghai, 200433, PR China. Electronic address: wlyang@fudan.edu.cn.

PMID: 31864018
DOI: 10.1016/j.biomaterials.2019.119680

Abstract

Long blood circulation is the basic requirement of advanced drug delivery systems for tumor treatment, which leads to enhanced tumor therapeutic efficiency and reduced side effects. However, the pharmacokinetics of the current nanoparticles in vivo is still unsatisfactory, which leads to limited success to translate nanoparticles into clinical applications. Inspired by the natural cell membrane-coating strategy, a series of zwitterionic polymer membranes are firstly developed and coated onto different kinds of nanoparticles in this work. Intriguingly, the zwitterionic polymer membrane shows stronger protein adsorption resistance and reduced macrophage uptake compared with the corresponding zwitterionic polymer brush or the red blood cell (RBC) membrane, which results in longer blood circulation time and higher tumor accumulation of the coated nanoparticles. Combined with the photothermal effect of model nanoparticles, Fe₃O₄, zwitterionic polymer membrane-coated Fe₃O₄ shows enhanced photothermal therapy (PTT) efficacy on A549 tumors compared with the corresponding zwitterionic polymer brush or RBC membrane-coated Fe₃O₄. Notably, Fe₃O₄ coated by carboxybetaine-based biomimic membranes exhibits the ultra-long blood circulation (t_1/2 = 96.0 h) and strongest PTT efficacy compared with those coated by phosphorylcholine-based or sulfobetaine-based biomimic membranes. In addition, the zwitterionic biomimic membrane exhibits rapid glutathione-triggered degradation with the products of low molecular weight (<2000 g mol^-1). Therefore, the biodegradable zwitterionic biomimic membrane coating offers a universal platform for the design and application of long-circulating biomedical nanoparticles, which may pave the way for the clinical applications of biomedical nanoparticles in tumor therapy.

Keywords: Drug delivery; Long circulation; Photothermal therapy; Protein adsorption; Zwitterionic polymer membrane.

Publication types

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

MeSH terms

Erythrocyte Membrane
Humans
Nanoparticles*
Neoplasms* / therapy
Photothermal Therapy
Polymers

Substances

Polymers