PDF(Pubmed)
Abstract：
Optical stimulation in the red/near infrared range recently gained increasing interest, as a not-invasive tool to control cardiac cell activity and repair in disease conditions. Translation of this approach to therapy is hampered by scarce efficacy and selectivity. The use of smart biocompatible materials, capable to act as local, NIR-sensitive interfaces with cardiac cells, may represent a valuable solution, capable to overcome these limitations. In this work, a far red-responsive conjugated polymer, namely poly[2,1,3-benzothiadiazole-4,7-diyl[4,4-bis(2-ethylhexyl)-4H-cyclopenta[2,1-b:3,4-b\']dithiophene-2,6-diyl]] (PCPDTBT) is proposed for the realization of photoactive interfaces with cardiomyocytes derived from pluripotent stem cells (hPSC-CMs). Optical excitation of the polymer turns into effective ionic and electrical modulation of hPSC-CMs, in particular by fastening Ca2+ dynamics, inducing action potential shortening, accelerating the spontaneous beating frequency. The involvement in the phototransduction pathway of Sarco-Endoplasmic Reticulum Calcium ATPase (SERCA) and Na+ /Ca2+ exchanger (NCX) is proven by pharmacological assays and is correlated with physical/chemical processes occurring at the polymer surface upon photoexcitation. Very interestingly, an antiarrhythmogenic effect, unequivocally triggered by polymer photoexcitation, is also observed. Overall, red-light excitation of conjugated polymers may represent an unprecedented opportunity for fine control of hPSC-CMs functionality and can be considered as a perspective, noninvasive approach to treat arrhythmias.
摘要：
在红色/近红外范围内的光学刺激最近获得了越来越多的兴趣，作为一种非侵入性工具来控制心脏细胞活动和在疾病条件下的修复。这种治疗方法的转化受到功效和选择性不足的阻碍。使用智能生物相容性材料，能够像当地人一样行动，与心脏细胞的NIR敏感界面，可能是一个有价值的解决方案，能够克服这些限制。在这项工作中,一种对红色有反应的共轭聚合物,即聚[2,1,3-苯并噻二唑-4,7-二基[4,4-双（2-乙基己基）-4H-环戊烷[2,1-b：3,4-b']二噻吩-2,6-二基]]（PCPDTBT）被提议用于实现与源自多能干细胞（hPSC-CMs）的心肌细胞的光敏界面。聚合物的光激发变成hPSC-CM的有效离子和电调制，特别是通过紧固Ca2+动力学，诱导动作电位缩短，加速自发跳动频率。通过药理学测定证明了Sarco-内质网钙ATPase（SERCA）和Na/Ca2交换剂（NCX）参与光转导途径，并且与光激发时在聚合物表面发生的物理/化学过程相关。非常有趣的是，一种抗心律失常作用,由聚合物光激发明确触发，也被观察到。总的来说,共轭聚合物的红光激发可能代表了对hPSC-CM功能的精细控制的前所未有的机会，可以被认为是一个观点，治疗心律失常的非侵入性方法。
