Sertaconazole-repurposed nanoplatform enhances lung cancer therapy via CD44-targeted drug delivery

Abstract

Background Lung cancer is one of the most frequent causes of cancer-related deaths worldwide. Drug repurposing and nano-drug delivery systems are attracting considerable attention for improving anti-cancer therapy. Sertaconazole (STZ), an antifungal agent, has been reported to exhibit cytotoxicity against both normal and tumor cells, and its medical use is limited by its poor solubility. In order to overcome such shortcomings, we prepared a drug-repurposed nanoplatform to enhance the anti-tumor efficiency. Methods Nanoplatform was prepared by thin film dispersion. Drug release studies and uptake studies were measured in vitro. Subsequently, we verified the tumor inhibition mechanisms of HTS NPs through apoptosis assay, immunoblotting and reactive oxygen species (ROS) detection analyses. Antitumor activity was evaluated on an established xenograft lung cancer model in vivo. Results Our nanoplatform improved the solubility of sertaconazole and increased its accumulation in tumor cells. Mechanistically, HTS NPs was dependent on ROS-mediated apoptosis and pro-apoptotic autophagy to achieve their excellent anti-tumor effects. Furthermore, HTS NPs also showed strong inhibitory ability in nude mouse xenograft models without significant side effects. Conclusions Our results suggest that sertaconazole-repurposed nanoplatform provides an effective strategy for lung cancer treatment.

Mitochondrial‐Targeted CS@KET/P780 Nanoplatform for Site‐Specific Delivery and High‐Efficiency Cancer Immunotherapy in Hepatocellular Carcinoma

“…Next, the cells were incubated with various concentrations of normal saline (NC), KET, IR780, P780, KET/P780 NPs, and CS@KET/P780 NPs for 4 and 6 h. Then the cells were exposed to laser radiation for 30 s at 660 nm (for P780, KET/P780 NPs, and CS@KET/P780 NPs) or 808 nm (for IR780) after discarding the growth media and rinsing them with normal saline and incubated for another 2 h. As previously reported, the absorbance was measured at a wavelength of 570 nm. [ 31 ] Colony formation test, as previously described, was used to assess cell proliferation. [ 32 ] In a nutshell, 500 cancer cells were cultivated in 24‐well plates before being exposed to the same reagent dose for 4 h. After saline washout, intervention was performed using 660 or 808 nm laser irradiation for 30 s (1.0 W cm −2 ).…”

Nanoplatform-Mediated Autophagy Regulation and Combined Anti-Tumor Therapy for Resistant Tumors

“…For example, Liu R et al synthesized HA-TPGS-STZ nanoparticles to co-delivery TPGS and autophagy activator Sertaconazole (STZ), generating ROS through TPGS to induce mitochondria-related apoptosis, while activating autophagy dependent apoptosis, significantly enhancing the therapeutic effect on lung cancer. 165 Besides, Kavya KV et al co-delivered curcumin and Bcl 2 siRNA through Poly@Cur-FA nanoparticles, which significantly enhanced the therapeutic efficacy of curcumin in cervical cancer by inhibiting Bcl2 to activate autophagy dependent cell death. 166 Similarly, Hanafy NAN et al synthesized Curcumin-Niacin NPs nanoparticles to co-deliver niacin and curcumin, activating the GPR109A/AMPK/NRF-2 signaling pathway to induce excess autophagy collaborated with curcumin, significantly improving the therapeutic efficacy in liver cancer.…”