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.
Keyphrases
- combination therapy
- cancer therapy
- photodynamic therapy
- reactive oxygen species
- drug delivery
- locally advanced
- endothelial cells
- induced apoptosis
- fluorescence imaging
- drug induced
- papillary thyroid
- oxidative stress
- single cell
- high throughput
- radiation therapy
- water soluble
- young adults
- binding protein
- climate change
- replacement therapy
- smoking cessation