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- W3209014018 abstract "Optimal combination of hydrophobic-hydrophilic balance, proton buffering and electrostatic interaction is the key issue for designing polycations as efficient gene vectors and antibacterial agents. Herein, we screened a series of pH-sensitive quaternary ammonium-based amphiphilic triblock copolymers, mPEG2k-P(DPAa/DMAb)-PQAc (TDDE-x), which had different pKa values and proton buffering capacities. Significantly, we found that both the highest siRNA intracellular delivery efficiency and the strongest antibacterial capacity occurred on TDDE-3 micelles with the segment structure of mPEG2k-P(DPA50/DMA56)-PQA55. The TDDE-3/siRNA complex achieved 67% silencing efficiency on H9C2 cells (N/P = 5, 50 nM siRNA), higher than the advanced commercial transfection reagents RNAiMAX (58%) and Lipo2000 (30%). Moreover, TDDE-3 micelles showed quite low MICs of 32 μg/mL and 8 μg/mL against E. coli and S. aureus, respectively. Further studies on the structure-function relationship indicated that TDDE-3 micelles could mediate robust endosome escape and siRNA cytosolic release, and strong bacterial cell membrane-destabilizing function. Undoubtedly, this work reveals the possibility for double optimization of siRNA intracellular delivery efficiency and antibacterial activity of amphiphilic polycations by reasonable structure design, which is significant for low-cost development and clinical translation of efficient multifunctional polycations." @default.
- W3209014018 created "2021-11-08" @default.
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- W3209014018 date "2022-01-01" @default.
- W3209014018 modified "2023-10-15" @default.
- W3209014018 title "Possibility for double optimization of siRNA intracellular delivery efficiency and antibacterial activity: Structure screening of pH-sensitive triblock amphiphilic polycation micelles" @default.
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- W3209014018 doi "https://doi.org/10.1016/j.colsurfb.2021.112178" @default.
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