Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore, Singapore.
College of Science, Harbin Engineering University, Harbin, 150080, China.
Nat Commun. 2018 Oct 15;9(1):4277. doi: 10.1038/s41467-018-06729-6.
An intelligent drug release system that is triggered into action upon sensing the motion of swarmer P. mirabilis is introduced. The rational design of the drug release system focuses on a pNIPAAm-co-pAEMA copolymer that prevents drug leakage in a tobramycin-loaded mesoporous silica particle by covering its surface via electrostatic attraction. The copolymer chains are also conjugated to peptide ligands YVLWKRKRKFCFI-NH that display affinity to Gram-negative bacteria. When swarmer P. mirabilis cells approach and come in contact with the particle, the copolymer-YVLWKRKRKFCFI-NH binds to the lipopolysaccharides on the outer membrane of motile P. mirabilis and are stripped off the particle surface when the cells move away; hence releasing tobramycin into the swarmer colony and inhibiting its expansion. The release mechanism is termed Motion-Induced Mechanical Stripping (MIMS). For swarmer B. subtilis, the removal of copolymers from particle surfaces via MIMS is not apparent due to poor adherence between bacteria and copolymer-YVLWKRKRKFCFI-NH system.
引入了一种智能药物释放系统，该系统能够在感应到 swarm P. mirabilis 的运动时触发。药物释放系统的合理设计侧重于 pNIPAAm-co-pAEMA 共聚物，该共聚物通过静电吸引覆盖其表面来防止载有妥布霉素的介孔硅颗粒中的药物泄漏。共聚物链也与肽配体 YVLWKRKRKFCFI-NH 缀合，该配体对革兰氏阴性菌具有亲和力。当 swarm P. mirabilis 细胞接近并与颗粒接触时，共聚物-YVLWKRKRKFCFI-NH 与运动 P. mirabilis 外膜上的脂多糖结合，当细胞移动时从颗粒表面脱落; 从而将妥布霉素释放到 swarm 菌落中并抑制其扩展。这种释放机制被称为运动诱导的机械剥落 (MIMS)。对于 swarm B. subtilis，由于细菌和共聚物-YVLWKRKRKFCFI-NH 系统之间的粘附不良，通过 MIMS 从颗粒表面去除共聚物并不明显。
