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具有卓越近红外荧光/光声成像性能和光热肿瘤治疗效果的治疗前诊断剂。

Pretheranostic agents with extraordinaryNIRF/photoacoustic imaging performanceand photothermal oncotherapy efficacy.

作者信息

Shi Liu, Chen Zhenzhou, Ou Jiaxin, Liang En, Chen Zhipeng, Fu Qiuyue, Huang Lan, Cheng Kui

机构信息

Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism and Guangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.

State Key Laboratory of Organ Failure Research, Key Laboratory of Infectious Diseases Research in South China, Ministry of Education, Southern Medical University, Guangzhou 510515, China.

出版信息

Acta Pharm Sin B. 2024 Dec;14(12):5370-5381. doi: 10.1016/j.apsb.2024.07.017. Epub 2024 Jul 24.

Abstract

Cervical cancer, the most common gynecological malignancy, significantly and adversely affects women's physical health and well-being. Traditional surgical interventions and chemotherapy, while potentially effective, often entail serious side effects that have led to an urgent need for novel therapeutic methods. Photothermal therapy (PTT) has emerged as a promising approach due to its ability to minimize damage to healthy tissue. Connecting a biothiol detection group to PTT-sensitive molecules can improve tumor targeting and further minimize potential side effects. In this study, we developed a near-infrared fluorescence (NIRF)/photoacoustic (PA) dual-mode probe, S-NBD, which demonstrated robust PTT performance. This innovative probe is capable of activating NIRF/PA signals to enable the detection of biothiols with high emission wavelength (838 nm) and large Stokes shift (178 nm), allowing for monitoring of cancer cells. Additionally, the probe achieved an outstanding photothermal conversion efficiency of 67.1%. The application of laser irradiation (660 nm, 1.0 W/cm, 5 min) was able to achieve complete tumor ablation without recurrence. In summary, this seminal study presents a pioneering NIRF/PA dual-mode dicyanoisophorone-based probe for biothiol imaging, incorporating features from PTT for the first time. This pioneering approach achieves the dual objectives of improving tumor diagnosis and treatment.

摘要

宫颈癌是最常见的妇科恶性肿瘤,对女性的身体健康和幸福有着重大的负面影响。传统的手术干预和化疗虽然可能有效,但往往会带来严重的副作用,这使得人们迫切需要新的治疗方法。光热疗法(PTT)因其能够将对健康组织的损伤降至最低而成为一种很有前景的方法。将生物硫醇检测基团与对PTT敏感的分子连接,可以提高肿瘤靶向性,并进一步减少潜在的副作用。在本研究中,我们开发了一种近红外荧光(NIRF)/光声(PA)双模探针S-NBD,它表现出强大的PTT性能。这种创新的探针能够激活NIRF/PA信号,以检测具有高发射波长(838 nm)和大斯托克斯位移(178 nm)的生物硫醇,从而实现对癌细胞的监测。此外,该探针的光热转换效率高达67.1%。应用激光照射(660 nm,1.0 W/cm,5分钟)能够实现肿瘤的完全消融且无复发。总之,这项开创性的研究首次提出了一种基于二氰异佛尔酮的NIRF/PA双模探针用于生物硫醇成像,并融入了PTT的特性。这种开创性的方法实现了改善肿瘤诊断和治疗的双重目标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6acf/11725032/3cca15d624c2/ga1.jpg

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