H2O2-Responsive amphiphilic polymer with aggregation-induced emission (AIE) for DOX delivery and tumor therapy

Ya-Xuan Liang; Xue-Yi Sun; De-Zhong Xu; Jun-Ru Huang; Quan Tang; Zhong-Lin Lu; Rui Liu

doi:10.1016/j.bioorg.2021.105559

H₂O₂-Responsive amphiphilic polymer with aggregation-induced emission (AIE) for DOX delivery and tumor therapy

Bioorg Chem. 2022 Feb:119:105559. doi: 10.1016/j.bioorg.2021.105559. Epub 2021 Dec 15.

Authors

Ya-Xuan Liang¹, Xue-Yi Sun¹, De-Zhong Xu², Jun-Ru Huang³, Quan Tang¹, Zhong-Lin Lu⁴, Rui Liu⁵

Affiliations

¹ College of Chemistry, Beijing Normal University, Beijing 100875, PR China.
² China National Institute for Food and Drug Control, Institute of Chemical Drug Control, TianTanXiLi 2, Beijing 100050, PR China.
³ College of Medicine, China Pharmaceutical University, Nanjing 210009, PR China.
⁴ College of Chemistry, Beijing Normal University, Beijing 100875, PR China. Electronic address: luzl@bnu.edu.cn.
⁵ College of Chemistry, Beijing Normal University, Beijing 100875, PR China. Electronic address: rliu@bnu.edu.cn.

PMID: 34952244
DOI: 10.1016/j.bioorg.2021.105559

Abstract

Stimuli-responsive drug delivery systems (DDSs) based on amphiphilic polymers have attracted much attention. In this study, we reported an innovative H₂O₂-responsive amphiphilic polymer (TBP), bearing a H₂O₂-sensitive phenylboronic ester, AIE fluorophore tetraphenylethene (TPE) hydrophobic, and polyethylene glycol hydrophilic (PEG) moieties. TBP could self-assemble into micelles with an encapsulation efficiency as high as 74.9% for doxorubicin (DOX) in aqueous solution. In the presence of H₂O₂, TBP micelles was decomposed by oxidation, hydrolysis and rearrangement, leading to almost 80% DOX release from TBP@DOX micelles. TBP and the corresponding degradation products were biocompatible, while TBP@DOX micelles only displayed obvious toxicity toward cancer cells. Drug delivery process was clearly monitored by confocal laser scanning microscopic (CLSM) and flow cytometry (FCM) analysis. Moreover, in vivo anticancer study showed that TBP@DOX micelles were accumulated in tumor region of nude mice and effectively inhibited tumor growth. The results suggested that the reported H₂O₂-responsive amphiphilic polymer displayed great potential in drug delivery and tumor therapy.

Keywords: Amphiphilic polymers; Drug delivery; H(2)O(2)-responsive; Tumor therapy.

Publication types

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

MeSH terms

Animals
Antibiotics, Antineoplastic / chemistry
Antibiotics, Antineoplastic / pharmacology*
Cell Proliferation / drug effects
Cell Survival / drug effects
Dose-Response Relationship, Drug
Doxorubicin / chemistry
Doxorubicin / pharmacology*
Drug Delivery Systems*
Drug Liberation
Drug Screening Assays, Antitumor
Female
HEK293 Cells
HeLa Cells
Humans
Hydrogen Peroxide / chemistry*
Mice
Mice, Inbred BALB C
Mice, Nude
Molecular Structure
Polymers / chemistry*
Protein Aggregates
Structure-Activity Relationship
Surface-Active Agents / chemistry*

Substances

Antibiotics, Antineoplastic
Polymers
Protein Aggregates
Surface-Active Agents
Doxorubicin
Hydrogen Peroxide