Mesoporous polydopamine delivery system for intelligent drug release and photothermal-enhanced chemodynamic therapy using MnO2 as gatekeeper

Zhaoyang Wang; Zekai Li; Yuehua Shi; Leyong Zeng

doi:10.1093/rb/rbad087

Mesoporous polydopamine delivery system for intelligent drug release and photothermal-enhanced chemodynamic therapy using MnO₂ as gatekeeper

Regen Biomater. 2023 Sep 22:10:rbad087. doi: 10.1093/rb/rbad087. eCollection 2023.

Authors

Zhaoyang Wang¹, Zekai Li¹, Yuehua Shi¹, Leyong Zeng¹

Affiliation

¹ Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Chemical Biology Key Laboratory of Hebei Province, State Key Laboratory of New Pharmaceutical Preparations and Excipients, College of Chemistry and Materials Science, Hebei University, Baoding 071002, P.R. China.

Abstract

The non-specific leakage of drugs from nanocarriers seriously weakened the safety and efficacy of chemotherapy, and it was very critical of constructing tumor microenvironment (TME)-responsive delivery nanocarriers, achieving the modulation release of drugs. Herein, using manganese dioxide (MnO₂) as gatekeeper, an intelligent nanoplatform based on mesoporous polydopamine (MPDA) was developed to deliver doxorubicin (DOX), by which the DOX release was precisely controlled, and simultaneously the photothermal therapy (PTT) and chemodynamic therapy (CDT) were realized. In normal physiological environment, the stable MnO₂ shell effectively avoided the leakage of DOX. However, in TME, the overexpressed glutathione (GSH) degraded MnO₂ shell, which caused the DOX release. Moreover, the photothermal effect of MPDA and the Fenton-like reaction of the generated Mn²⁺ further accelerated the cell death. Thus, the developed MPDA-DOX@MnO₂ nanoplatform can intelligently modulate the release of DOX, and the combined CDT/PTT/chemotherapy possessed high-safety and high-efficacy against tumors.

Keywords: MnO2 gatekeeper; chemodynamic therapy; chemotherapy; mesoporous polydopamine; photothermal therapy.