Platinum(IV) complex-based two-in-one polyprodrug for a combinatorial chemo-photodynamic therapy

Area of Science:

• Biomedical Engineering
• Materials Science
• Oncology

Background:

• Combinatorial therapy enhances treatment efficacy but faces limitations like tumor hypoxia.
• Chemotherapy and photodynamic therapy (PDT) combination is hindered by hypoxia, reducing antitumor efficacy.

Purpose of the Study:

• To develop a platinum(IV) complex-based polyprodrug for combined chemotherapy and oxygen-independent PDT.
• To address tumor hypoxia limitations in combined anticancer therapies.

Main Methods:

• Synthesized a nanosized hydrogel-like polyprodrug via in situ polymerization of a platinum(IV) complex-based prodrug monomer (PPM) and MPC.
• Investigated photoactivation of the polyprodrug to generate platinum(II) species and reactive oxygen species (ROS) without oxygen consumption.
• Utilized electron spin resonance (ESR) and fluorescence probes to confirm ROS generation.

Main Results:

• The polyprodrug successfully generated platinum(II) chemotherapeutics and ROS upon light exposure, independent of oxygen.
• The nanosized, photoresponsive polyprodrug demonstrated sustained drug release, prolonged circulation, and tumor accumulation.
• The treatment reversed multidrug resistance by downregulating MRP1 expression.

Conclusions:

• The developed platinum(IV) polyprodrug offers a promising strategy for overcoming tumor hypoxia in cancer therapy.
• This oxygen-independent, photoactivable system provides sustained drug delivery and enhances antitumor efficacy.
• The polyprodrug exhibits potential for reversing drug resistance and improving overall cancer treatment outcomes.