4.7 Article

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

Journal

CARBOHYDRATE POLYMERS
Volume 268, Issue -, Pages -

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2021.118237

Keywords

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

Funding

  1. National NaturalScience Foundation of China [81974434]
  2. Science and Technology of Guangdong Province [2020A0505100038, 2018A0303130233, 2018A050506021, 2018A050506019, 2018A050506040]
  3. Science and Technology Program of Guangzhou [201907010037, 201907010032]

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The novel T7 peptide-modified nanoparticles based on carboxymethyl chitosan can target lung cancer cells, precisely regulate drug release, and improve treatment effects.
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-CMCSBAPE, 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 mu g/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 microenvironment to promote the inhibition of tumor growth. Collectively, the current findings help lay the foundation for combinatorial lung cancer treatment.

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