The Surface charge of nanocarriers inevitably affects drug delivery efficiency, however, the cancer cell specificity, anti-inflammatory

 

Abstract

The Surface charge of nanocarriers inevitably affects drug delivery efficiency, however, the cancer cell specificity, anti-inflammatory effects and charge-reversal points remain to be further addressed in biomedical application. The aim of this study was to comprehensively assess the cancer cell specificity of DOX-loaded mesoporous silica-chitosan oligosaccharide-carboxymethyl chitosan nanoparticles (DOX@MSNs-COS-CMC) in MCF-7 and Hela cells, inhibit the production of inflammatory cytokines and improve the drug accumulation in tumor site. Intracellular results reveal that the retention time prolonged to 48 h in both Hela and MCF-7 cells at pH 7.4. However, DOX@MSNs-COS-CMC exhibited a cell type-dependent cytotoxicity and enhanced intracellular uptake in Hela cells at pH 6.5, due to the clathrin-mediated endocytosis and macropinocytosis in Hela cells in comparison with the vesicular transport in MCF-7 cells. Moreover, pearson's correlation coefficient value significantly decreased to 0.25 after 8 h, prompting endosomal escape and drug delivery into HeLa nucleus. After treatment of MSNs-COS-CMC at 200 g/mL, the inflammatory cytokines IL-6 and TNF-α level decreased by 70% and 80%, respectively. Tumor-inhibition of DOX@MSNs-COS-CMC was 0.4 times higher than free DOX, alleviating cardiotoxicity and inflammation in Hela xenograft tumor model. Charge-reversible DOX@MSNs-COS-CMC could be a possible candidate for clinical therapy of cervical carcinoma.

PMID: 32223247 [PubMed - as supplied by publisher]

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