Issue 5, 2023

Pt(ii) metallacycles encapsulated by ferritin enable precise cancer combination chemo-photodynamic therapy

Abstract

Different from common anti-tumor drugs, organoplatinum(II) metallacycles can integrate imaging and other therapeutic capabilities by incorporating corresponding functional donor ligands to enable potential applications in biomedicine. However, most of the emerging therapeutic agents not only show poor solubility and selectivity but also have serious side effects and unsatisfactory efficacy and encounter the tendency to develop drug resistance due to their single treatment model. Herein, an organoplatinum(II) metallacycle (PtM) was designed and synthesized using coordination-driven self-assembly via the combination of a metallic chemotherapy precursor and a reactive oxygen species generating organic precursor. The hydrophobic PtM molecules were encapsulated in the cavity of human heavy chain ferritin (HFn) during the reassembly of HFn to prepare the active targeting nanoagent HFn-PtM for use in chemo-photodynamic combination therapy. The HFn-PtM nanoagents exhibited excellent stability in buffer (pH from 5 to 7.2), alleviating the concern of drug leakage during circulation. A cellular uptake assay indicated that HFn-PtM could efficiently enter specific cells that overexpress the transferrin receptor 1. In vitro and in vivo anti-tumor investigations revealed that HFn-PtM exhibited excellent anti-tumor efficiency with negligible systemic toxicity. This work provides a strategy for the easy construction of multifunctional organoplatinum-based tumor-targeted drugs.

Graphical abstract: Pt(ii) metallacycles encapsulated by ferritin enable precise cancer combination chemo-photodynamic therapy

Supplementary files

Article information

Article type
Paper
Submitted
28 Oct 2022
Accepted
10 Dec 2022
First published
12 Dec 2022

J. Mater. Chem. B, 2023,11, 1090-1099

Pt(II) metallacycles encapsulated by ferritin enable precise cancer combination chemo-photodynamic therapy

X. Min‡, M. Li‡, W. Zhang‡, R. Li, Z. Zhang, P. Wang, W. Su, F. Li, Y. Sun and Y. Liu, J. Mater. Chem. B, 2023, 11, 1090 DOI: 10.1039/D2TB02349K

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