Chitosan-based nanoparticle co-delivery of docetaxel and curcumin ameliorates anti-tumor chemoimmunotherapy in lung cancer

Carbohydr Polym. 2021 Sep 15:268:118237. doi: 10.1016/j.carbpol.2021.118237. Epub 2021 May 21.

Abstract

The application of traditional chemotherapy drugs for lung cancer has obvious limitations, such as toxic side effects, uncontrolled drug-release, poor bioavailability, and drug-resistance. Thus, to address the limitations of free drugs and improve treatment effects, we developed novel T7 peptide-modified nanoparticles (T7-CMCS-BAPE, CBT) based on carboxymethyl chitosan (CMCS), which is capable of targeted binding to the transferrin receptor (TfR) expressed on lung cancer cells and precisely regulating drug-release according to the pH value and reactive oxygen species (ROS) level. The results showed that the drug-loading content of docetaxel (DTX) and curcumin (CUR) was approximately 7.82% and 6.48%, respectively. Good biosafety was obtained even when the concentration was as high as 500 μg/mL. More importantly, the T7-CMCS-BAPE-DTX/CUR (CBT-DC) complexes exhibited better in vitro and in vivo anti-tumor effects than DTX monotherapy and other nanocarriers loaded with DTX and CUR alone. Furthermore, we determined that CBT-DC can ameliorate the immunosuppressive micro-environment to promote the inhibition of tumor growth. Collectively, the current findings help lay the foundation for combinatorial lung cancer treatment.

Keywords: Carboxymethyl chitosan; Curcumin; Immunosuppressive micro-environment; Lung cancer; T7 peptide.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Cell Line, Tumor
  • Chitosan / analogs & derivatives
  • Chitosan / metabolism
  • Chitosan / pharmacokinetics
  • Chitosan / toxicity
  • Curcumin / chemistry
  • Curcumin / pharmacokinetics
  • Curcumin / therapeutic use*
  • Docetaxel / chemistry
  • Docetaxel / pharmacokinetics
  • Docetaxel / therapeutic use*
  • Drug Carriers / chemistry*
  • Drug Carriers / metabolism
  • Drug Carriers / pharmacokinetics
  • Drug Carriers / toxicity
  • Drug Liberation
  • Humans
  • Hydrogen-Ion Concentration
  • Lung / pathology
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Macrophages / drug effects
  • Mice
  • Myeloid-Derived Suppressor Cells / drug effects
  • Nanoparticles / chemistry*
  • Nanoparticles / metabolism
  • Nanoparticles / toxicity
  • Reactive Oxygen Species / metabolism
  • T-Lymphocytes / drug effects
  • Tumor Microenvironment / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Reactive Oxygen Species
  • carboxymethyl-chitosan
  • Docetaxel
  • Chitosan
  • Curcumin