State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300350, P. R. China.
University of Groningen and University Medical Center Groningen, Department of Biomedical Engineering, Antonius Deusinglaan 1, Groningen 9713 AV, The Netherlands.
J Mater Chem B. 2022 Apr 6;10(14):2316-2322. doi: 10.1039/d1tb02647j.
Self-targeting antimicrobial platforms have yielded new possibilities for the treatment of infectious biofilms. Self-targeting involves stealth transport through the blood circulation towards an infectious biofilm, where the antimicrobial platform penetrates and accumulates in a biofilm in response to a change in environmental conditions, such as local pH. In a final step, nano-antimicrobials need to be activated or the antimicrobial cargo of nanocarriers released. Zwitterions possess both cationic and anionic groups, allowing full reversal in zeta potential from below to above zero in response to a change in environmental conditions. Electrolyte-based platforms generally do not have the ability to change their zeta potentials from below to above zero. Zwitterions for use in self-targeting platforms are usually hydrophilic and have a negative charge under physiological conditions (pH 7.4) providing low adsorption of proteins and assisting blood circulation. However, near or in the acidic environment of a biofilm, they become positively-charged yielding targeting, penetration and accumulation in the biofilm through electrostatic double-layer attraction to negatively-charged bacteria. Response-times to pH changes vary, depending on the way the zwitterion or electrolyte is built in a platform. Self-targeting zwitterion-based platforms with a short response-time yield different accumulation kinetics in abdominal biofilms in living mice than platforms with a longer response-time. experiments in mice also proved that self-targeting, pH-responsive zwitterion-based platforms provide a feasible approach for clinical control of bacterial infections. Clinically however, also other conditions than infection may yield an acidic environment. Therefore, it remains to be seen whether pH is a sufficiently unique recognition sign to direct self-targeting platforms to an infectious biofilm or whether (additional) external targeting through near-infrared irradiation or magnetic field application is needed.
自靶向抗菌平台为治疗感染性生物膜提供了新的可能性。自靶向涉及通过血液循环进行隐形运输，靶向抗菌平台针对环境条件（如局部 pH 值）的变化穿透并积聚在生物膜中。在最后一步中，需要激活纳米抗菌剂或释放纳米载体的抗菌货物。两性离子同时具有阳离子和阴离子基团，允许在环境条件发生变化时，其 zeta 电位从低于零反转到高于零。基于电解质的平台通常没有能力将其 zeta 电位从低于零反转到高于零。用于自靶向平台的两性离子通常是亲水的，在生理条件下（pH 值 7.4）带负电荷，从而降低了对蛋白质的吸附并有助于血液循环。然而，在生物膜的酸性环境附近或其中，它们会带正电荷，通过静电双层吸引作用靶向、穿透并积聚在带负电荷的细菌中。对 pH 值变化的响应时间取决于平台中两性离子或电解质的构建方式。与具有较长响应时间的平台相比，具有较短响应时间的基于自靶向两性离子的平台在活鼠的腹部生物膜中产生不同的积累动力学。在小鼠中的实验还证明，基于自靶向、pH 响应的两性离子平台为临床控制细菌感染提供了一种可行的方法。然而，在临床上，除了感染之外，其他条件也可能导致酸性环境。因此，pH 是否是一个足够独特的识别标志，能够将自靶向平台引导到感染性生物膜，或者是否需要（额外的）通过近红外辐射或磁场应用进行外部靶向，仍有待观察。
