Construction of Urokinase-Type Plasminogen Activator Receptor-Targeted Heterostructures for Efficient Photothermal Chemotherapy against Cervical Cancer To Achieve Simultaneous Anticancer and Antiangiogenesis

Abstract

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 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.

Bacterially Synthesized Tellurium Nanorods for Elimination of Advanced Malignant Tumor by Photothermal Immunotherapy

“…It was found that there was inappreciable change in the temperature elevation after four repeated irradiation cycles, revealing remarkable photothermal stability of Te@EcN (Figure 2j). Furthermore, the time constant (τ s ) was measured to be 383.2 s, and photothermal conversion efficiency (η) was calculated to be 33.5% (Figure 2k,l), which was comparable to previously reported photothermal agents, such as gold nanorods (30.6%), [45] palladium nanosheets (30.9%), [46] and carbon-silica nanocomposite (34.5%). [47] Together, these results demonstrated the superior NIR photothermal performance and high photostability of Te@ EcN, thus confirming its potential for PTT of tumors.…”

An Overview of Novel Agents for Cervical Cancer Treatment by Inducing Apoptosis: Emerging Drugs Ongoing Clinical Trials and Preclinical Studies

“…In 1995, researchers announced the first liposome-based nanodrug, doxorubicin, for the treatment of tumors (79). Afterwards, with continuous advent of new polymer materials, a mass of nanoparticles (nanospheres, nano capsules) have been discovered and have exhibited significant selectivity and efficiency for drug loading and tumor therapy (80)(81)(82). This research has inspired new concepts in nanomedicine, and photothermal effects combined with diagnostic imaging or with drugs bring forward new types of combination therapies.…”

The use of a uPAR-targeted probe for photothermal cancer therapy prolongs survival in a xenograft mouse model of glioblastoma

“…uPAR is a receptor known to be overexpressed in multiple tumor types and is therefore a promising target for anti-cancer therapy [ 13 , 16 , 27 ]. AE105 is a small peptide that binds to uPAR and has previously been used for imaging and targeted therapy [ 18 , 28 , 29 ]. The strong uPAR expression at the invasive tumor front and surrounding stroma makes it highly interesting for guided tumor resection, and more recently the fluorescent probe composed of ICG and AE105, ICG-Glu-Glu-AE105, has been applied for fluorescence-guided surgery [ 30 , 31 ].…”