Marasini Ramesh, Aryal Santosh
Department of Chemistry, College of Arts and Sciences, Kansas State University, Manhattan, Kansas 66506, United States.
Russell H. Morgan Department of Radiology and Radiological Sciences, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States.
ACS Omega. 2022 Mar 28;7(14):12056-12065. doi: 10.1021/acsomega.2c00306. eCollection 2022 Apr 12.
Organic small-molecule photosensitizers are well-characterized and known for the light-responsive treatment modality including photodynamic therapy. Compared with ultraviolet-visible (UV-vis) light used in conventional photodynamic therapy with organic photosensitizers, near-infrared (NIR) light from 700 to 900 nm is less absorbed and scattered by biological tissue such as hemoglobin, lipids, and water, and thus, the use of NIR excitation can greatly increase the penetration depth and emission. Additionally, NIR light has lower energy than UV-vis that can be beneficial due to less activation of fluorophores present in tissues upon NIR irradiation. However, the low water stability, nonspecific distribution, and short circulation half-life of the organic photosensitizers limit its broad biological application. NIR responsive small-molecule fluorescent agents are the focus of extensive research for combined molecular imaging and hyperthermia. Recently a new class of NIR dye, IR-820 with excitation and emission wavelengths of 710 and 820 nm, has been developed and explored as an alternative platform to overcome some of the limitations of the most commonly used gold nanoparticles for photothermal therapy of cancer. Herein, we synthesized a core-shell biocompatible nanocarrier envelope made up of a phospholipid conjugated with poly(ethylene glycol) as a shell, while poly(lactic glycolic acid) (PLGA) was used as a core to encapsulate IR-820 dye. The IR-820-loaded nanoparticles were prepared by nanoprecipitation and characterized for their physicochemical properties and photothermal efficiency. These nanoparticles were monodispersed and highly stable in physiological pH with the hydrodynamic size of 103 ± 8 nm and polydispersity index of 0.163 ± 0.031. The IR-820-loaded nanocarrier showed excellent biocompatibility in the dark, whereas remarkable phototoxicity was observed with breast cancer cells (MCF-7) upon NIR laser excitation. Therefore, the IR-820-loaded phospholipid mimicking biodegradable lipid-polymer composite nanoparticles could have great potential for cancer theranostics.
有机小分子光敏剂具有良好的特性，以包括光动力疗法在内的光响应治疗方式而闻名。与传统光动力疗法中使用有机光敏剂的紫外 - 可见光（UV-vis）相比，700至900纳米的近红外（NIR）光被血红蛋白、脂质和水等生物组织吸收和散射较少，因此，使用近红外激发可以大大增加穿透深度和发射。此外，近红外光的能量低于紫外 - 可见光，这是有益的，因为近红外照射时组织中存在的荧光团活化较少。然而，有机光敏剂的低水稳定性、非特异性分布和短循环半衰期限制了其广泛的生物学应用。近红外响应小分子荧光剂是分子成像和热疗联合研究的重点。最近，一类新型近红外染料IR - 820被开发出来，其激发和发射波长分别为710和820纳米，并被探索作为一种替代平台，以克服最常用的金纳米颗粒在癌症光热治疗中的一些局限性。在此，我们合成了一种核壳生物相容性纳米载体包膜，其外壳由与聚乙二醇共轭的磷脂组成，而聚乳酸 - 乙醇酸共聚物（PLGA）用作核心来封装IR - 820染料。通过纳米沉淀法制备了负载IR - 820的纳米颗粒，并对其物理化学性质和光热效率进行了表征。这些纳米颗粒在生理pH下呈单分散且高度稳定，流体动力学尺寸为103±8纳米，多分散指数为0.163±0.031。负载IR - 820的纳米载体在黑暗中显示出优异的生物相容性，而在近红外激光激发下，乳腺癌细胞（MCF - 7）表现出显著的光毒性。因此，负载IR - 820的磷脂模拟可生物降解脂质 - 聚合物复合纳米颗粒在癌症诊疗方面具有巨大潜力。
