Prostate Cancer-Targeting Liposome Loaded with Zinc Ion-Coordinated Photosensitizer for Enhanced Chemo-Photodynamic Therapy

Background: Prostate cancer (PCa) is the second most prevalent cancer in males globally, impacting one out of every six males. However, the therapeutic effect of chemotherapy on PCa is restricted. Methods: To address this, we developed a tumor-targeted multifunctional liposomal platform (PTX-PS/Zn@Lip-Apt) for zinc-enhanced chemo-photodynamic therapy of PCa. Co-delivery of PTX and an aggregation-induced emission photosensitizer (TPEDPD) enables combined chemotherapy and photody-namic therapy. Zinc ions were loaded into liposomes to improve the chemosensitivity of PCa to chemodrugs. Then, the AS1411 aptamer was further modified onto the sur-face of the liposome to enhance its tumor targeting ability. Moreover, to improve the cellular uptake efficiency of the nanoparticles, the photochemical internalization (PCI) strategy was also employed. Results: In vitro experiments indicated that aptamer conjugation and PCI application enhanced the cellular uptake and cytotoxicity of PTX/PS-Zn@Lip-Apt. The zinc ion enhanced cytotoxicity could also be found. In vivo experiments demonstrated the good antitumor effect and biosafety of PTX/PS-Zn@Lip-Apt. Conclusions: Our findings provide an important basis for innovatively applying zinc-enhanced combined chemo-photodynamic therapy in prostate cancer.