International Journal of Nanomedicine (Oct 2020)
Novel T7-Modified pH-Responsive Targeted Nanosystem for Co-Delivery of Docetaxel and Curcumin in the Treatment of Esophageal Cancer
Abstract
Lian Deng,1,* Xiongjie Zhu,1,* Zhongjian Yu,1 Ying Li,1 Lingyu Qin,1 Zhile Liu,1 Longbao Feng,2 Rui Guo,2 Yanfang Zheng1 1Department of Oncology, Zhujiang Hospital of Southern Medical University, Guangzhou 510282, China; 2Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China*These authors contributed equally to this workCorrespondence: Yanfang Zheng; Rui Guo Tel +86 18665000236Email [email protected]; [email protected]: Although single-drug chemotherapy is still an effective treatment for esophageal cancer, its long-term application is limited by severe side-effects, poor bioavailability, and drug-resistance. Increasing attention has been paid to nanomedicines because of their good biological safety, targeting capabilities, and high-efficiency loading of multiple drugs. Herein, we have developed a novel T7 peptide-modified pH-responsive targeting nanosystem co-loaded with docetaxel and curcumin for the treatment of esophageal cancer.Methods: Firstly, CM-β-CD-PEI-PEG-T7/DTX/CUR (T7-NP-DC) was synthesized by the double emulsion (W/O/W) method. The targeting capacity of the nanocarrier was then investigated by in vitro and in vivo assays using targeted (T7-NP) and non-targeted nanoparticles (NP). Furthermore, the anti-tumor efficacy of T7-NP-DC was studied using esophageal cancer cells (KYSE150 and KYSE510) and a KYSE150 xenograft tumor model.Results: T7-NP-DC was synthesized successfully and its diameter was determined to be about 100 nm by transmission electron microscopy and dynamic light scattering. T7-NP-DC with docetaxel and curcumin loading of 10% and 6.1%, respectively, had good colloidal stability and exhibited pH-responsive drug release. Good biosafety was observed, even when the concentration was as high as 800 μg/mL. Significant enhancement of T7-NP uptake was observed 6 hours after intravenous injection compared with NP. In addition, the therapeutic efficacy of T7-NP-DC was better than NP-DC and docetaxel in terms of growth suppression in the KYSE150 esophageal cancer model.Conclusion: The findings demonstrated that T7-NP-DC is a promising, non-toxic, and controllable nanoparticle that is capable of simultaneous delivery of the chemotherapy drug, docetaxel, and the Chinese Medicine, curcumin, for treatment of esophageal cancer. This novel T7-modified targeting nanosystem releases loaded drugs when exposed to the acidic microenvironment of the tumor and exerts a synergistic anti-tumor effect. The data indicate that the nanomaterials can safely exert synergistic anti-tumor effects and provide an excellent therapeutic platform for combination therapy of esophageal cancer.Keywords: nanocarrier, T7 peptide, pH-responsive, docetaxel, esophageal cancer
