Photo-responsive prodrug nanoparticles for efficient cytoplasmic delivery and synergistic photodynamic-chemotherapy of metastatic triple-negative breast cancer

Triple-negative breast cancer (TNBC) have been considered as the most malignant subtype of breast cancer with leading incidence and mortality among females. Herein, photo-responsive prodrug nanoparticles (AlP/CPT-NPs) were designed with efficient cytoplasmic delivery of anti-cancer agent for cooperative photodynamic-chemotherapy. AlP/CPT-NPs were prepared using photosensitizer Al(III) phthalocyanine chloride disulfonic acid (AlP) and ROS-activatable camptothecin prodrug (CPT-PD). AlP/CPT-NPs could induce intracellular O-1(2) generation upon light exposure, which not only initiate immediate disassembly of AlP/CPT-NPs but also promote cytoplasmic delivery of CPT through O-1(2) -mediated lysosomal rupture. The released intracellular CPT could be translocated into nuclei in only 5 min post-irradiation. Consequently, AlP/CPT-NPs efficiently suppressed the tumor growth and metastasis of TNBC in a spatiotemporally controlled manner, providing a promising option for effective treatment of metastatic TNBC. Statement of significance Breast cancer is a complex disease with leading incidence among females, in which triple-negative breast cancer (TNBC) is considered as the most malignant subtype with increased risk of resistance, recurrence and metastasis. Herein, we designed photo-responsive prodrug nanoparticles (AlP/CPT-NPs) for synergistic treatment of metastatic TNBC. Upon 660 nm light exposure, the O-1(2) generated by AlP/CPT- NPs could initiate immediate disassembly of AlP/CPT-NPs and further promote cytoplasmic delivery of the therapeutic payloads (camptothecin, CPT). The prepared AlP/CPT-NPs induced potent in vivo phototherapeutic damage through photodynamic-chemotherapy, resulting in complete tumor ablation with metastasis suppression. (C) 2021 Published by Elsevier Ltd on behalf of Acta Materialia Inc.

Automated summary

In this study, photo-responsive prodrug nanoparticles (AlP/CPT-NPs) were designed for synergistic treatment of metastatic TNBC. Upon light exposure, the generated O-1(2) could promote cytoplasmic delivery of the therapeutic payloads, resulting in potent in vivo phototherapeutic damage through photodynamic-chemotherapy. This approach led to complete tumor ablation with metastasis suppression, showing promise for effective treatment of metastatic TNBC.