TY - JOUR
T1 - Possibility for double optimization of siRNA intracellular delivery efficiency and antibacterial activity
T2 - Structure screening of pH-sensitive triblock amphiphilic polycation micelles
AU - Zhang, Yufeng
AU - Dong, Yanliang
AU - Zhou, Junhui
AU - Huang, Wenjun
AU - Wu, Yidi
AU - Zhao, Shuyue
AU - Shi, Yongli
AU - Bai, Suping
AU - Li, Chunhui
AU - Huang, Yuanyu
AU - Dong, Anjie
N1 - Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2022/1
Y1 - 2022/1
N2 - 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.
AB - 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.
KW - Amphiphilic triblock polycations
KW - Antibacterial activity
KW - Hydrophobic-hydrophilic balance
KW - Proton buffering capacity
KW - SiRNA delivery
UR - http://www.scopus.com/inward/record.url?scp=85118508191&partnerID=8YFLogxK
U2 - 10.1016/j.colsurfb.2021.112178
DO - 10.1016/j.colsurfb.2021.112178
M3 - Article
C2 - 34742020
AN - SCOPUS:85118508191
SN - 0927-7765
VL - 209
JO - Colloids and Surfaces B: Biointerfaces
JF - Colloids and Surfaces B: Biointerfaces
M1 - 112178
ER -