A pH-Responsive Charge-Convertible Drug Delivery Nanocarrier for Precise Starvation and Chemo Synergistic Oncotherapy

Yifei Zhou; Xuan Gao; Yu Lu; Ruohao Zhang; Kehong Lv; Jitong Gong; Jing Feng; Hongjie Zhang

doi:10.1002/cplu.202200394

A pH-Responsive Charge-Convertible Drug Delivery Nanocarrier for Precise Starvation and Chemo Synergistic Oncotherapy

Chempluschem. 2023 Feb;88(2):e202200394. doi: 10.1002/cplu.202200394.

Authors

Yifei Zhou^{1

2}, Xuan Gao^{1

2}, Yu Lu^{1

3}, Ruohao Zhang^{1

2}, Kehong Lv^{1

2}, Jitong Gong^{1

2}, Jing Feng^{1

2}, Hongjie Zhang^{1

2

4}

Affiliations

¹ State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.
² School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, P. R. China.
³ College of Chemistry, Jilin University, Changchun, 130012, P. R. China.
⁴ Department of Chemistry, Tsinghua University, Beijing, 100084, P. R. China.

PMID: 36725346
DOI: 10.1002/cplu.202200394

Abstract

A pH-responsive charge-convertible drug delivery nanocarrier (MSN-TPZ-GOx@ZnO@PAH-PEG-DMMA, abbreviated as MTGZ@PPD) was prepared, which could specifically release hypoxia-activated chemotherapeutic Tirapazamine (TPZ) and glucose oxidase (GOx) in the tumor site for precise starvation and chemo synergistic oncotherapy. Acid-responsive Schiff base structure modified mesoporous silica nanoparticles (MSN) co-load with GOx and TPZ, then link with ZnO quantum dots (QDs). PAH-PEG-DMMA (PPD) polymer makes MTGZ@PPD with biocompatibility and charge-convertible feature. MTGZ@PPD is negatively charged at physiological pH, and the charge reversal of PPD and acidolysis of the Schiff base structure under the acidic tumor microenvironment (TME) induce a positively charged surface, which could potentiate the cell internalization. ZnO QDs could decompose at acidic TME, achieving controllable drug release. GOx could starve the tumor cells and enhance hypoxia level, thus initiates the activation of TPZ to realize synergistic starvation therapy and chemotherapy. This intelligent MTGZ@PPD has shown great potential for starvation and chemo synergistic oncotherapy.

Keywords: charge-convertible; glucose oxidase; pH-responsive; synergistic oncotherapy; tirapazamine.

Publication types

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

MeSH terms

Doxorubicin* / chemistry
Hydrogen-Ion Concentration
Schiff Bases
Zinc Oxide* / chemistry

Substances

Doxorubicin
Zinc Oxide
2,3-dimethylmaleic anhydride
Schiff Bases