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基于主客体识别的超分子卟啉光敏剂用于原位细菌响应性近红外光热治疗

Supramolecular Porphyrin Photosensitizers Based on Host-Guest Recognition for In Situ Bacteria-Responsive Near-Infrared Photothermal Therapy.

作者信息

Wu Dan, Du Xianlong, Xue Qiangqiang, Zhou Jie, Ping Kunmin, Cao Yibin, Liu Shuang, Zhu Qing

机构信息

College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou, 310014, P. R. China.

Bethune First Clinical Medical College, Jilin University, Changchun, 130012, P. R. China.

出版信息

Adv Healthc Mater. 2024 Dec;13(30):e2401662. doi: 10.1002/adhm.202401662. Epub 2024 Oct 10.

DOI:10.1002/adhm.202401662
PMID:39388515
Abstract

Antibiotic resistance resulting from the overuse of antibiotics sets a high challenge for brutal antimicrobial treatment. Although photothermal therapy (PTT) overcomes the awkward situation of antibiotic resistance, it usually mistakenly kills the beneficial bacteria strains when eliminating pernicious bacteria. Specifically recognizing and damaging the target pathogens is urgently required for PTT-mediated sterilization strategy. Based on the host-guest recognition between cucurbit[10]uril (CB[10]) and porphyrins, two water-soluble supramolecular porphyrins are designed and implement selective bactericidal effect via in situ bacteria-responsive near-infrared (NIR) PTT. With the help of CB[10], the π-π stacking and hydrophobic interactions of porphyrins are efficiently inhibited, thus contributing to a good photostability and a high photothermal conversion efficiency. Attributing to the matching reduction potential between facultative anaerobic Escherichia coli (E. coli) and porphyrins, they are selectively in situ reduced into supramolecular phlorin and supramolecular chlorin by E. coli, successfully achieving a selective sterilization against E. coli. In vivo, the in situ bacteria-responsive NIR PTT systems also promote the quick recovery of E. coli-infected abscesses and trauma on mice without inducing obvious systemic toxicity, providing a new alternative to the current antibiotics and helping relieve the global public health crisis of abusive antibiotics.

摘要

抗生素的过度使用导致的抗生素耐药性给残酷的抗菌治疗带来了巨大挑战。尽管光热疗法(PTT)克服了抗生素耐药性的尴尬局面,但在消除有害细菌时,它通常会误杀有益菌株。PTT介导的杀菌策略迫切需要特异性识别并破坏目标病原体。基于葫芦[10]脲(CB[10])与卟啉之间的主客体识别,设计了两种水溶性超分子卟啉,并通过原位细菌响应近红外(NIR)PTT实现了选择性杀菌效果。在CB[10]的帮助下,卟啉的π-π堆积和疏水相互作用被有效抑制,从而具有良好的光稳定性和高光热转换效率。由于兼性厌氧大肠杆菌(E. coli)与卟啉之间的还原电位匹配,它们被大肠杆菌选择性地原位还原为超分子二氢卟酚和超分子二氢卟吩,成功实现了对大肠杆菌的选择性杀菌。在体内,原位细菌响应近红外PTT系统还能促进感染大肠杆菌的小鼠脓肿和创伤的快速恢复,且不会引起明显的全身毒性,为当前的抗生素提供了新的替代品,有助于缓解滥用抗生素带来的全球公共卫生危机。

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