An efficient synergistic cancer therapy by integrating cell cycle inhibitor and photosensitizer into polydopamine nanoparticles

Abstract

Multifunctional nanomedicines are highly demanded in the development of new cancer theranostic approaches to achieve more effective and safer treatment. Herein, we designed a polydopamine (PDA) nanoparticle by loading with cell cycle inhibitor nocodazole (NOC) and photosensitizer ZnPc(TAP)₄¹²⁺ (ZnPc12⁺) for simultaneous tumor imaging and efficient synergistic therapy. It was found that the loaded NOC can facilitate enhanced nuclear uptake of ZnPc12⁺ in MCF-7 cells, resulting in PDA-NOC–ZnPc12⁺ nanoparticles not only inhibiting cell proliferation and inducing cell cycle G₂/M arrest, but also improving photodynamic therapy (PDT) efficacy. Compared with the respective single anticancer action, PDA-NOC–ZnPc12⁺ nanoparticles exhibited better anticancer efficacy in tumor-bearing mice, demonstrating the synergistic effect of combination therapy with a cell cycle inhibitor and photosensitizer. Particularly, PDA-NOC–ZnPc12⁺ resulted in a high accumulation of ZnPc12⁺ in tumors but low retention in livers, without rendering distinct toxicity to the treated animals. Such PDA-based nanocarriers functionalized with dual-drug loading and bioimaging may have great potential for diagnosis and combination therapy of cancer.