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

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-mod...

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Bibliographic Details
Published in:Carbohydrate polymers 2021-09, Vol.268, p.118237, Article 118237
Main Authors: Zhu, Xiongjie, Yu, Zhongjian, Feng, Longbao, Deng, Lian, Fang, Zhaobi, Liu, Zhile, Li, Ying, Wu, Xiaoran, Qin, Lingyu, Guo, Rui, Zheng, Yanfang
Format: Article
Language:English
Subjects:
Carboxymethyl chitosan
Curcumin
Immunosuppressive micro-environment
Lung cancer
T7 peptide
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Summary: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. •ROS/pH-responsive nanoparticles mediated DTX and CUR co-delivery to lung cancer.•The nanomedicine exhibited better antitumor effects compared with free drug.•Amelioration of immunosuppressive microenvironment could be achieved by CBT-DC.
ISSN:0144-8617
1879-1344
DOI:10.1016/j.carbpol.2021.118237