Folate-receptor-targeted laser-activable poly(lactide-co-glycolic acid) nanoparticles loaded with paclitaxel/indocyanine green for photoacoustic/ultrasound imaging and chemo/photothermal therapy.
Folate-receptor-targeted laser-activable poly(lactide-co-glycolic acid) nanoparticles loaded with paclitaxel/indocyanine green for photoacoustic/ultrasound imaging and chemo/photothermal therapy.
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DOI：
10.2147/ijn.s167043
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发表时间：
2018
影响因子：
8
通讯作者：
Ran H
中科院分区：
文献类型：
--
作者：
Liu F;Chen Y;Li Y;Guo Y;Cao Y;Li P;Wang Z;Gong Y;Ran H
癌症是对人类健康最严重的威胁之一。精准医学是一种创新的治疗方法，作为其中的一部分，治疗诊断纳米医学已得到广泛研究。然而，纳米药物所需的生物相容性和批准的高昂成本阻碍了其临床转化。我们设计了一种新型治疗诊断纳米颗粒（NP）叶酸受体靶向激光激活聚（丙交酯-乙醇酸）（PLGA）纳米颗粒，负载有紫杉醇（Ptx）/吲哚青绿（ICG）-叶酸-聚乙二醇（PEG）-PLGA-Ptx@ICG-全氟己烷 (Pfh)-使用安全且经批准的材料和药物，这将有助于临床转化。通过激光照射，可以实现高效的光热治疗。此外，通过近红外激光照射特定区域可以激活靶向纳米颗粒，从而导致叶酸受体高表达区域的Ptx急剧释放，并确保肿瘤区域内较高的Ptx浓度，从而产生化疗/光热协同抗肿瘤功效。同时，纳米颗粒可用作光声和超声成像的双模态造影剂。通过超声处理方法制备 FA-PEG-PLGA-Ptx@ICG-Pfh NPs，并对其理化性质进行表征。分别通过CCK8测定和血液分析评估细胞毒性和体内生物相容性。通过光声/超声成像系统在体外和体内评估纳米粒子作为双模态造影剂。通过CCK8测定和MDA-MB231荷瘤小鼠模型评价体外抗癌作用和体内抗癌治疗。 FA-PEG-PLGA-Ptx@ICG-Pfh NPs尺寸为308±5.82 nm，具有负zeta电位，表现出优异的光热效应。纳米粒子在激光照射下可引发Ptx的急剧释放，并在体外和体内表现出良好的生物相容性。通过光声/超声成像，纳米粒子在体外和体内表现出作为双模态造影剂的优异能力。激光照射下的 FA-PEG-PLGA-Ptx@ICG-Pfh NPs 在体外和体内均表现出最佳的抗癌功效。这种生物相容性的新型治疗诊断NP有望将双模态成像与改善的治疗效果结合起来，并为癌症治疗提供一个有前景的范例。
Cancer is one of the most serious threats to human health. Precision medicine is an innovative approach to treatment, as part of which theranostic nanomedicine has been studied extensively. However, the required biocompatibility and substantial cost for the approval of nanomedicines hinder their clinical translation. We designed a novel type of theranostic nanoparticle (NP) folate-receptor-targeted laser-activatable poly(lactide-co-glycolic acid) (PLGA) NPs loaded with paclitaxel (Ptx)/indo-cyanine green (ICG)-folic acid-polyethylene glycol (PEG)-PLGA-Ptx@ICG-perfluorohexane (Pfh)- using safe and approved materials and drugs, which would facilitate clinical translation. With laser irradiation, highly efficient photothermal therapy can be achieved. Additionally, targeted NPs can be activated by near-infrared laser irradiation at a specific region, which leads to the sharp release of Ptx at areas of high folate-receptor expression and ensures a higher Ptx concentration within the tumor region, thereby leading to chemo/photothermal synergistic antitumor efficacy. Meanwhile, the NPs can be used as a dual-modality contrast agent for photoacoustic and ultrasound imaging. FA-PEG-PLGA-Ptx@ICG-Pfh NPs were prepared by sonification method and characterized for physicochemical properties. Cytotoxicity and in vivo biocompatibility were evaluated respectively by CCK8 assay and blood analysis. NPs as dual-modality contrast agents were evaluated by photoacoustic/ultrasound imaging system in vitro and in vivo. In vitro anticancer effect and in vivo anticancer therapy was evaluated by CCK8 assay and MDA-MB231 tumor-bearing mice model. FA-PEG-PLGA-Ptx@ICG-Pfh NPs were in the size of 308±5.82 nm with negative zeta potential and showed excellent photothermal effect. The NPs could be triggered sharp release of Ptx by laser irradiation, and showed the good biocompatibility in vitro and in vivo. Through photoacoustic/ultrasound imaging, the NPs showed an excellent ability as dual-modality contrast agents in vitro and in vivo. FA-PEG-PLGA-Ptx@ICG-Pfh NPs with laser irradiation showed the best anticancer efficacy in vitro and in vivo. Such a biocompatible and novel theranostic NP is expected to integrate dual-modality imaging with improved therapeutic efficacy and provide a promising paradigm for cancer therapy.