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Construction of Urokinase Type Plasminogen Activator Receptor (uPAR)-Targeted Heterostructures for Efficient Photothermal-Chemotherapy against Cervical Cancer to Achieve Simultaneous Anticancer and Antiangiogenesis.

Rational design and construction of theranostic nanomedicines based on clinical characteristics of cervical cancer is an important strategy to achieve precise cancer therapy. Herein, we fabricate a cervical cancer-targeting gold nanorod-mesoporous silica heterostructure for co-delivery of synergistic cisplatin and antiangiogenic drug Avastin (cisplatin-AuNRs@SiO2-Avastin@PEI/AE105) to achieve synergistic chemo-photothermal therapy. Based on database analysis and clinical samples staining, conjugation of AE105 targeting peptide obviously improves the intracellular uptake of the nanosystem, and enhances the cancer-killing ability and selectivity between cervical cancer and normal cells. It could also be used to specifically monitor urokinase plasminogen activator receptor (uPAR) expression level in clinical cervical specimens, which would be an early indicator of prognosis in cancer treatment. Under 808 nm laser irradiation, the nanosystem demonstrates smart NIR-light-triggered drug release and prominent photodynamic activity via induction of ROS overproduction-mediated cell apoptosis. The nanosystem also simultaneously suppresses HeLa tumor growth and angiogenesis in vivo, with no evident histological damage observed in the major organs. In short, this study not only provides a clinical data-based rational design strategy of smart nanomedicine for precise treatment and rapid clinical diagnosis of cervical cancer, but also contributes to the development of the clinical translation of nanomedicines.