Abstract：
An electro-chemo-responsive carrier has been engineered for the controlled release of a highly hydrophilic anticancer peptide, CR(NMe)EKA (Cys-Arg- N-methyl-Glu-Lys-Ala). Remotely controlled on demand release of CR(NMe)EKA, loaded in electro-responsive poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticles, has been achieved by applying electrical stimuli consisting of constant positive (+0.50 V) or negative voltages (-0.50 V) at pre-defined time intervals. In addition, after loading CR(NMe)EKA/PEDOT nanoparticles into an injectable pH responsive hydrogel formed by phenylboronic acid grafted to chitosan (PBA-CS), the efficiency of the controlled peptide release has increased approximately by a factor of 2.6. The hydration ratio of such hydrogel is significantly lower in acidic environments than in neutral and basic media, which has been attributed to the dissociation of the boronate bonds between polymer chains. Hence, the electro-controlled peptide release from PBA-CS/CR(NMe)EKA/PEDOT hydrogels, in the acidic environment of tumors, combines the effects of the oxidation and reduction of PEDOT chains on the interactions with the peptide and the carrier, with the peptide concentration gradient at the interface between the collapsed hydrogel and the release medium. Furthermore, the peptide released by electro-stimulation preserved its bioactivity assessed by promoting human prostate cancer cells death. Overall, this work is a promising attempt to develop a carrier platform for small hydrophilic anticancer peptides, which delivery rationale is synergistically regulated by the electrical and pH responsiveness of the carrier.
摘要：
已经设计了一种电化学响应载体，用于高度亲水的抗癌肽的受控释放，CR(NMe)EKA(Cys-氩-N-甲基-Glu-Lys-Ala)。按需遥控释放CR(NMe)EKA，负载在电响应聚（3,4-亚乙基二氧噻吩）（PEDOT）纳米颗粒中，通过以预定义的时间间隔施加由恒定的正电压(+0.50V)或负电压(-0.50V)组成的电刺激来实现。此外,在将CR（NMe）EKA/PEDOT纳米颗粒加载到由苯基硼酸接枝到壳聚糖（PBA-CS）形成的可注射pH响应性水凝胶中之后，控制肽释放的效率增加了大约2.6倍。这种水凝胶的水合率在酸性环境中明显低于在中性和碱性介质中，这归因于聚合物链之间的硼酸酯键的解离。因此，PBA-CS/CR（NMe）EKA/PEDOT水凝胶的电控制肽释放，在肿瘤的酸性环境中，结合了PEDOT链的氧化和还原对肽和载体相互作用的影响，在塌陷的水凝胶和释放介质之间的界面处具有肽浓度梯度。此外，通过电刺激释放的肽保留了其通过促进人类前列腺癌细胞死亡评估的生物活性。总的来说,这项工作是开发小型亲水性抗癌肽载体平台的有希望的尝试，其递送原理由载体的电和pH响应性协同调节。
