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O-经济化肿瘤靶向光敏磁性纳米材料在胃癌诊断与治疗中的整合

Integration of O-economised tumour-targeted photosensitive magnetic nanomaterials in the diagnosis and therapy of gastric cancer.

作者信息

Situ JinRong, Yang Yingying, Zhang Lingle, Yan Hongzhang, Cheng Yingsheng

机构信息

College of Fisheries and Life Science of Shanghai Ocean University Shanghai 201306 China

Shanghai Jiao Tong University Affiliated Sixth People's Hosptial China.

出版信息

RSC Adv. 2024 Mar 25;14(14):9920-9932. doi: 10.1039/d4ra00497c. eCollection 2024 Mar 20.

Abstract

Hypoxia in the tumour microenvironment is a major limiting factor in photodynamic therapy. The present study employed a novel O-economised photosensitizer, ACSN, to effectively curtail oxygen consumption by impeding the aerobic respiration of tumour cells, thereby increasing the reactive oxygen species (ROS) production in photodynamic therapy. To enhance the efficacy of photodynamic therapy, the active targeting peptide iRGD was employed to facilitate drug accumulation in the tumour tissue. Therefore, we constructed a targeted drug platform, ACSN/FeO@MSNs-iRGD, that integrates diagnosis and treatment. The drug exhibited excellent active targeting ability towards gastric cancer MGC-803 cells and can efficiently penetrate the mitochondria upon cellular internalisation. The photosensitizer ACSN, released from the drug, effectively suppressed mitochondrial aerobic respiration to conserve oxygen and exhibited robust ROS production upon laser excitation. The core-shell structure comprises FeO, which offers excellent T2 dark contrast for real-time tumour monitoring through MRI imaging. By incorporating excellent photodynamic therapy and MRI imaging capabilities, this drug can serve as an effective platform for the integration of tumour diagnosis and treatment, thus addressing the limitations associated with conventional tumour therapies. It is anticipated that this approach will soon be clinically translated.

摘要

肿瘤微环境中的缺氧是光动力治疗的主要限制因素。本研究采用了一种新型的氧节约型光敏剂ACSN,通过阻碍肿瘤细胞的有氧呼吸来有效减少氧气消耗,从而在光动力治疗中增加活性氧(ROS)的产生。为了提高光动力治疗的疗效,采用了活性靶向肽iRGD来促进药物在肿瘤组织中的积累。因此,我们构建了一个集诊断与治疗于一体的靶向药物平台ACSN/FeO@MSNs-iRGD。该药物对胃癌MGC-803细胞表现出优异的主动靶向能力,细胞内化后能有效穿透线粒体。从药物中释放出来的光敏剂ACSN有效抑制线粒体有氧呼吸以保存氧气,并在激光激发时表现出强大的ROS产生能力。核壳结构包含FeO,通过磁共振成像可为实时肿瘤监测提供优异的T2暗对比度。通过整合优异的光动力治疗和磁共振成像能力,这种药物可作为肿瘤诊断与治疗一体化的有效平台,从而解决传统肿瘤治疗方法的局限性。预计这种方法很快将实现临床转化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3019/10961965/48efd0644636/d4ra00497c-f1.jpg

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