随着全球范围内抗生素的滥用，耐药菌广泛流行，有关抗耐药菌感染的新策略已成为迫在眉睫的新课题。已成功用于治疗多种肿瘤的光动力学疗法正逐渐应用于抗菌治疗，但由于目前大多数光敏剂存在靶向性差、穿透深度有限等诸多不足，限制了该疗法的推广。本项目拟在已成功建立可大量合成高纯度单羧基取代酞菁的基础上，通过取代其羧基基团，将具有生物特性的"靶向装置"（如抗菌肽等）偶合到酞菁上，合成具有一定靶向性的抗菌光敏剂，增强其对病原菌的杀伤选择性。同时，将合成的靶向光敏剂与稀土上转换纳米颗粒偶联，研制可治疗深部组织感染的上转换纳米靶向酞菁光敏剂，并开展近红外激发的细胞及动物水平的光动力学抗深部组织感染研究。预期本项目研制的上转换纳米靶向光敏剂不仅能有效治疗深部组织病原菌（包括耐药菌）感染，而且能将病原菌的检测及成像等诸多功能集于一体，在病原微生物诊疗领域具有重要应用。

In the last decades the worldwide rise in the emergence and spread of drug-resistant pathogens has intensified the development of new anti-microbial agents. Photodynamic antimicrobial chemotherapy (PACT) has been used successfully to inactivate pathogenic microorganisms in vitro, but its use to treat infections in animal models or patients has not, as yet, been much developed. The shortcomings of this method include the limited penetration depth and the lack of species specificity. We have previously established a method to synthesize unsymmetrical ZnPc-COOH in large quantity. Through the carboxyl group of ZnPc-COOH, it is possible to couple ZnPc with some targeting peptides in order to enhance the anti-microbial specificity. Meanwhile, these modified photosensitizers will be conjugated to the surface of upconversion nanoparticles. Using these phthalocyanine photosensitizers coupled with upconversion nanoparticles, we plan to carry out the near-infrared-triggered deep-tissue PACT study in vitro and in vivo. We expect that some modified photosensitizers coupled with lanthanide-doped upconversion nanoparticles will not only effective in the treatment of deep tissue infection, but also can be developed for integrated applications in pathogenic microorganisms detection and treatment.