文献：Elaboration on the architecture of pH-sensitive surface charge-adaptive micelles with enhanced penetration and bactericidal activity in bioflms

文献链接：https://jnanobiotechnology.biomedcentral.com/articles/10.1186/s12951-021-00980-8

作者：Rong Guo, Keke Li, Baocheng Tian, Changrong Wang, Xiangjun Chen, Xinyu Jiang, Huayu He and Wei Hong

相关产品：

PLA5K-PAE5K-mPEG5K  聚乳酸（5K）-聚（β-氨基酯）（5K）-甲氧基聚乙二醇（5K）

PAE5K-PLA5K-mPEG5K  聚（β-氨基酯）（5K）-聚乳酸（5K）-甲氧基聚乙二醇（5K）

PLA5K-PEG5K-PAE5K  聚乳酸（5K）-聚乙二醇（5K）-聚（β-氨基酯）（5K）

原文摘要：

Background: Bioflm formation is one of the main reasons for persistent bacterial infections. Recently, pH-sensitive copolymers have fascinated incredible attention to tackle bioflm-related infections. However, the proper incorporation of pH-sensitive segments in the polymer chains, which could signifcantly afect the bioflms targeting ability, has not been particularly investigated. Herein, we synthesized three types of pH-sensitive copolymers based on poly (β-amino ester) (PAE), poly (lactic-co-glycolic acid) (PLA) and polyethylene glycol (PEG), PAE-PLA-mPEG (A-L-E), PLAPAE-mPEG (L-A-E) and PLA-PEG-PAE (L-E-A) to address this issue.

Results: The three copolymers could self-assemble into micelles (MA-L-E, ML-A-E and ML-E-A) in aqueous medium. Compared with MA-L-E and ML-A-E, placing the PAE at the distal PEG end of PLA-PEG to yield PLA-PEG-PAE (ML-E-A) was characterized with proper triggering pH, fully bioflm penetration, and high cell membrane binding afnity. Further loaded with Triclosan (TCS), ML-E-A/TCS could efciently kill the bacteria either in planktonic or bioflm mode. We reasoned that PAE segments would be preferentially placed near the surface and distant from the hydrophobic PLA segments. This would increase the magnitude of surface charge-switching capability, as the cationic PAE+ would easily disassociate from the inner core without conquering the additional hydrophobic force arising from covalent linkage with PLA segments, and rapidly rise to the outermost layer of the micellar surface due to the relative hydrophilicity. This was signifcant in that it could enable the micelles immediately change its surface charge where localized acidity occurred, and efciently bind themselves to the bacterial surface where they became hydrolyzed by bacterial lipases to stimulate release of encapsulated TCS even a relatively short residence time to prevent rapid wash-out. In vivo therapeutic performance of ML-E-A/TCS was evaluated on a classical bioflm infection model, implant-related bioflm infection.

The result suggested that ML-E-A/TCS was efective for the treatment of implant-related bioflm infection, which was proved by the efcient clearance of bioflm-contaminated catheters and the recovery of surrounding infected tissues.

Conclusions: In summary, elaboration on the architecture of pH-sensitive copolymers was the frst step to target bioflm. The ML-E-A structure may represent an interesting future direction in the treatment of bioflm-relevant infections associated with acidity

PLA-PAE-mPEG、PLA-PEG-PAE和PAE-PLA-mPEG可能是指包含聚乳酸（PLA）、聚（β-氨基酯）（PAE）和甲氧基聚乙二醇（mPEG）的不同结构或顺序的共聚物。这三种共聚物都包含PLA、PAE和mPEG三种成分，但它们的排列顺序可能不同。由于PLA、PAE和mPEG各自具有性能，因此这三种共聚物可能具有优良的生物相容性、生物降解性、水溶性、低免疫原性和靶向性等。在化合物载体和组织工程等领域中，这三种共聚物可能具有潜在的应用价值。该文献制备三种ph敏感共聚物，PLA-PAE-mPEG、PAE-mPEG、PLA-PLA-mPEG和PLA-PEG-PEE分布不同。三种共聚物分别以聚乙二醇为稳定壳，PLA为疏水核，PAE为ph敏感的疏水核，自组装成ML-A-E、MA-L-E和ML-E-A胶束。对Te触发pH进行了初步研究。

图为：详细阐述了ph敏感共聚物与适当的pHt

PLA-PAE-mPEG、PLA-PEG-PAE和PAE-PLA-mPEG在表面电荷自适应胶束制备中的应用：

采用薄膜水化法制备了三种ph敏感的表面电荷自适应胶束（ML-A-E、MA-L-E和ML-E-A）。简单地说，将PLA-PAE-mPEG、PLA-PEG-PAE和PAE-PLA-mPEG分别溶解在二氯甲烷中。通过旋转蒸发去除溶剂，使flm形成。然后，用 PBS水合flm，通过flm搅拌得到胶束溶液。最后，将ML-E-A、ML-A-E和MA-L-E的pH分别调整。每个胶束制备的Te zeta在纳米ZS分析仪上测量了zeta电位。

图为：ML-E-A和ML-A-E的Zeta电势(A)和粒径(B)随时间的变化

结论：应用三种对ph敏感的共聚物，PLA-PAE-mPEG、PAE-PLA-mPEG和PLA-PEG-PAE可以自组装成三种ph敏感的表面电荷自适应胶束（ML-A-E、MA-L-E和ML-E-A），并重点研究了它们的结构-功能关系。与ML-A-E和MA-L-E相比，ML-E-A在切换表面电荷、与bacteria结合、穿透生物膜以及在体内treat生物膜相关方面具有更强的能力。综上所述，在构建生物膜处理时，需要考虑合理设计ph敏感共聚物的结构，以最大限度地提高电荷开关能力。