Chitosan-based nanoparticles (NPs) are widely used in drug delivery, device-based therapy, tissue engineering, and medical imaging. In this aspect, a clear understanding of how physicochemical properties of these NPs affect the cytological response is in high demand. The objective of this study is to evaluate the effect of surface charge on cellular uptake profiles (rate and amount) and intracellular trafficking. We fabricate three kinds of NPs (∼ 215 nm) with different surface charge via SPG membrane emulsification technique and deposition method. They possess uniform size as well as identical other physicochemical properties, minimizing any differences between the NPs except for surface charge. Moreover, we extend our research to eight cell lines, which could help to obtain a representative conclusion. Results show that the cellular uptake rate and amount are both positively correlated with the surface charge in all cell line. Subsequent intracellular trafficking indicates that some of positively charged NPs could escape from lysosome after being internalized and exhibit perinuclear localization, whereas the negatively and neutrally charged NPs prefer to colocalize with lysosome. These results are critical in building the knowledge base required to design chitosan-based NPs to be used efficiently and specifically.

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Conventional micellar carriers disassemble into free surfactants when diluted at concentrations below the critical micelle concentration (CMC). This limits the bioavailability in vivo of injected hydrophobic drugs encapsulated in micellar systems. Here, we show that a micelle comprising a superhydrophilic zwitterionic polymer domain and a superhydrophobic lipid domain has an undetectable CMC below 10−6 mM, a value that is orders of magnitude lower than the CMCs (>10−3 mM) of typical micellar systems. We also show that zwitterionic moieties or zwitterionic polymers added into a micelle solution stabilize the micelles at concentrations below their inherent CMC. In a mouse model of melanoma, ultralow CMC micelles encapsulating docetaxel led to the complete eradication of tumors, whereas conventional docetaxel micellar formulations did not reverse tumor growth. Ultralow-CMC micelles might become next-generation carriers for drug delivery.

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