Novel T7-Modified pH-Responsive Targeted Nanosystem for Co-Delivery of Docetaxel and Curcumin in the Treatment of Esophageal Cancer

Int J Nanomedicine. 2020 Oct 9:15:7745-7762. doi: 10.2147/IJN.S257312. eCollection 2020.

Abstract

Background: 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: T7 peptide; docetaxel; esophageal cancer; nanocarrier; pH-responsive.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Curcumin / administration & dosage
  • Curcumin / chemistry*
  • Curcumin / pharmacology*
  • Curcumin / therapeutic use
  • Docetaxel / administration & dosage
  • Docetaxel / chemistry*
  • Docetaxel / pharmacology*
  • Docetaxel / therapeutic use
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Esophageal Neoplasms / drug therapy*
  • Humans
  • Hydrogen-Ion Concentration
  • Nanomedicine
  • Nanoparticles / chemistry*
  • Polyethylene Glycols / chemistry
  • Polyethyleneimine / analogs & derivatives
  • Polyethyleneimine / chemistry
  • Tumor Microenvironment / drug effects

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • poly(ethylene glycol)-co-poly(ethyleneimine)
  • Docetaxel
  • Polyethylene Glycols
  • Polyethyleneimine
  • Curcumin

Grants and funding

This work was supported by a grant from the National Natural Science Foundation of China (No. 81974434), a grant from the Natural Science Foundation of Guangdong Province (No. 2018A0303130233), grants from the Science and Technology of Guangdong Province (Nos. 2018A050506021, 2018A050506019, 2018A050506040), and grants from the Science and Technology Program of Guangzhou (Nos. 201907010037, 201907010032).