Department of Ultrasound, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, PR China.
Department of Radiology, Hospital (t.c.m) Affiliated to Southwest Medical University, Luzhou 646000, PR China.
Biomater Sci. 2019 Oct 1;7(10):4060-4074. doi: 10.1039/c9bm01052a. Epub 2019 Sep 2.
Combined photothermal-chemotherapy guided by multimodal imaging is a promising strategy for cancer diagnosis and treatment. Multifunctional nanoparticles, such as those comprising organic and inorganic compounds, have been extensively investigated for combined photothermal-chemotherapy; however, their application is still limited by their potential long-term toxicity and lack of contrast properties. To solve these problems, in this study, a new type of multifunctional nanoparticle for combined photothermal-chemotherapy guided by dual-modality imaging was prepared with endogenous melanin by multistep emulsification to enhance tumor ablation. The nanoparticles were coated with poly(lactide-co-glycolic acid) (PLGA) and loaded with paclitaxel (PTX), encapsulated melanin and perfluoropentane (PFP). The materials in the nanoparticles were endogenous, ensuring high stability, biocompatibility, and biosafety. Nanoparticles irradiated with a laser, which induced their phase transformation into microbubbles, exhibited high photothermal conversion efficiency, thereby achieving photoacoustic (PA)/ultrasound (US) dual-modality imaging to determine tumor location, boundary, and size and to monitor drug distribution. Furthermore, optical droplet vaporization (ODV) of the nanoparticles could trigger the release of PTX; thus, these nanoparticles are a useful drug carrier. In vivo and in vitro experiments revealed that a strong synergistic antitumor effect was achieved by combining the photothermal properties of the nanoparticles with a chemotherapy drug. Importantly, the cavitation, thermoelastic expansion, and sonoporation caused by the phase transformation of the nanoparticles could directly damage the tumors. These processes also promoted the release, penetration and absorption of the drug, further enhancing the effect of combined photothermal-chemotherapy on tumor suppression. Therefore, the multifunctional nanoparticles prepared in this study provide a new strategy of using endogenous materials for controlled near-infrared (NIR)-responsive drug release and combined photothermal-chemotherapy guided by multimodal imaging.
多模态成像引导的光热-化学联合治疗是癌症诊断和治疗的一种有前途的策略。包含有机和无机化合物的多功能纳米粒子已被广泛研究用于光热-化学联合治疗；然而，它们的应用仍然受到潜在的长期毒性和缺乏对比特性的限制。为了解决这些问题，在本研究中，通过多步乳化制备了一种新型的基于双模态成像的多功能纳米粒子用于光热-化学联合治疗，以增强肿瘤消融效果。该纳米粒子用内源性黑色素进行了涂层，并负载了紫杉醇（PTX）、封装黑色素和全氟戊烷（PFP）。纳米粒子中的材料是内源性的，以确保其具有高稳定性、生物相容性和生物安全性。用激光照射纳米粒子会诱导其相变为微泡，从而表现出高的光热转换效率，实现了光声（PA）/超声（US）双模态成像，以确定肿瘤的位置、边界和大小，并监测药物分布。此外，纳米粒子的光学液滴蒸发（ODV）可以触发 PTX 的释放；因此，这些纳米粒子是一种有用的药物载体。体内和体外实验表明，将纳米粒子的光热特性与化疗药物相结合可实现强烈的协同抗肿瘤效果。重要的是，纳米粒子相变引起的空化、热弹性膨胀和声孔作用可以直接破坏肿瘤。这些过程还促进了药物的释放、渗透和吸收，进一步增强了联合光热-化学治疗对肿瘤抑制的效果。因此，本研究中制备的多功能纳米粒子为使用内源性材料实现近红外（NIR）响应性药物释放和多模态成像引导的联合光热-化学治疗提供了一种新策略。
