Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 11, Issue 43, Pages 39688-39705Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.9b15751
Keywords
uPAR targeting; heterostructure; photothermal-chemotherapy; antiangiogenesis; theranosis; cervical cancer
Funding
- Natural Science Foundation of China [81671809, 21877049, 21701051]
- Major Program for Tackling Key Problems of Industrial Technology in Guangzhou [201902020013]
- Dedicated Fund for Promoting High-Quality Marine Economic Development in Guangdong Province [GDOE-2019-A31]
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Rational design and construction of theranostic nano medicines 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 codelivery of synergistic cisplatin and antiangiogenic drug Avastin (cisplatin-AuNRs@SiO2-Avastin@PEI/AE105) to achieve synergistic chemophotothermal therapy. Based on database analysis and clinical sample staining, conjugation of the 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 the urokinase-type 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 reactive oxygen species 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.
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