Cell Type-Dependent Specificity and Anti-Inflammatory Effects of Charge-Reversible MSNs-COS-CMC for Targeted Drug Delivery in Cervical Carcinoma

• DOI: 10.1021/acs.molpharmaceut.0c00004
• Publication Date: 2020-03-30T19:20:31Z
• Authors: Lan Cui; Xiayi Feng; Wentao Liu; Hao Liu; Qian Qin; Shuangxia Wu; Suqin He; Xinchang Pang; Dong Men; Chengshen Zhu
• Keywords: Chitosan; Interleukin-6; Tumor Necrosis Factor-alpha; cell specificity; Anti-Inflammatory Agents; Uterine Cervical Neoplasms; 02 engineering and technology; Hydrogen-Ion Concentration; Models, Biological; Endocytosis; 3. Good health; MCF-7 Cells; chitosan oligosaccharide; Humans; Female; cervical carcinoma; 0210 nano-technology; charge reversal; anti-inflammatory; HeLa Cells

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 applications. 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 the 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 the HeLa nucleus. After the treatment of MSNs-COS-CMC at 200 μg/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 the HeLa xenograft tumor model. Charge-reversible DOX@MSNs-COS-CMC could be a possible candidate for clinical therapy of cervical carcinoma.