Coassembling functionalized glycopolypeptides to prepare pH-responsive self-indicating nanocomplexes to manipulate self-assembly/drug delivery and visualize intracellular drug release

Junyang Zhong; Yusi Quan; Xiaoya Zhao; Suifei Li; Ziqing He; Guodong Ye; Mingna Sun; Yingling Miao; Chunping Ma; Huikang Yang; Xing Chen; Yugang Huang

doi:10.1016/j.msec.2022.112711

Coassembling functionalized glycopolypeptides to prepare pH-responsive self-indicating nanocomplexes to manipulate self-assembly/drug delivery and visualize intracellular drug release

Biomater Adv. 2022 Mar:134:112711. doi: 10.1016/j.msec.2022.112711. Epub 2022 Feb 14.

Authors

Junyang Zhong¹, Yusi Quan¹, Xiaoya Zhao¹, Suifei Li¹, Ziqing He¹, Guodong Ye¹, Mingna Sun¹, Yingling Miao¹, Chunping Ma², Huikang Yang³, Xing Chen⁴, Yugang Huang⁵

Affiliations

¹ Key Laboratory of Molecular Target & Clinical Pharmacology, the State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China.
² School of Materials and Energy Engineering, Guizhou Institute of Technology, Guiyang 550003, China.
³ Department of Radiology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510640, China.
⁴ School of Public Health, Guangxi Medical University, Nanning 530021, China.
⁵ Key Laboratory of Molecular Target & Clinical Pharmacology, the State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China. Electronic address: hyug@gzhmu.edu.cn.

PMID: 35581069
DOI: 10.1016/j.msec.2022.112711

Abstract

The pH-responsive polymeric micelles (PMs) have been widely used as smart nano drug delivery systems to treat tumors. However, synchronously manipulating these PMs' self-assembly properties, drug release dynamics and tracing their pH-dependent intracellular fate remain challenges. Herein, we have first synthesized hyaluronic acid (HA) based glycopolypeptides modified by tetraphenylethylene (TPE) and a pH-sensitive doxorubicin (DOX) prodrug through Diels-Alder reaction, respectively. Then, the pH-responsive nanocomplexes (NCs) were prepared by coassembling the two obtained glycopolypeptides with different formulations. Controllable size within the range of 60-125 nm and morphologies like spherical, vesicular and oblate micelles can be easily accomplished by using this method; High drug encapsulating and loading efficiency can be easily realized and adjusted within a range of 86-97% and 7-25%, respectively; Acid sensitive drug release dynamics of these NCs are also tunable by using this way. Additionally, the programmed drug release induced by subtle pH variations can be extracellularly self-indicated by detecting the blue AIE changes of the TPE units through fluorescence resonance energy transfer (FRET) effect between DOX and TPE. More importantly, the dynamic pH-triggered DOX release can be easily traced inside the tumor cells by visualizing blue emission changes of the TPE through the FRET effect. In addition, both the size and the shape can affect the endocytic routes of the NCs; The HA coated NCs targeting the tumor cells can effectively inhibit the proliferation of the HeLa cells. This work can provide a new route to acquire the stimuli-responsive self-indicating PMs with the ability to adjust their self-assembly properties and their pH-triggered drug release dynamics, and even to simultaneously visualize the PMs' intracellular fate in a real-time.

Keywords: AIE; Drug delivery; Fluorescence resonance energy transfer; Glycopolypeptide; pH-responsive polymeric micelles.

MeSH terms

Doxorubicin / chemistry
Drug Delivery Systems* / methods
Drug Liberation
HeLa Cells
Humans
Hyaluronic Acid / chemistry
Hydrogen-Ion Concentration
Micelles*
Polymers / chemistry

Substances

Micelles
Polymers
Doxorubicin
Hyaluronic Acid