do Reis Sara Rhaissa Rezende, Helal-Neto Edward, da Silva de Barros Aline Oliveira, Pinto Suyene Rocha, Portilho Filipe Leal, de Oliveira Siqueira Luciana Betzler, Alencar Luciana Magalhães Rebelo, Dahoumane Si Amar, Alexis Frank, Ricci-Junior Eduardo, Santos-Oliveira Ralph
Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Rua Helio de Almeida, 75, Ilha do Fundão, Rio de Janeiro, Brazil.
Faculty of Pharmacy, Rio de Janeiro Federal University, Rio de Janeiro, Brazil.
Pharm Res. 2021 Feb;38(2):335-346. doi: 10.1007/s11095-021-02999-w. Epub 2021 Feb 18.
Melanoma is an invasive and very aggressive skin cancer due to its multi-drug resistance that results in poor patient survival. There is a need to test new treatment approaches to improve therapeutic efficacy and reduce side effects of conventional treatments.
PLA/PVA nanoparticles carrying both Dacarbazine and zinc phthalocyanine was produced by double emulsion technique. The characterization was performed by dynamic light scattering and atomic force microscopy. In vitro photodynamic therapy test assay using MV3 melanoma cells as a model has been performed. In vitro cell viability (MTT) was performed to measure cell toxicity of of nanoparticles with and without drugs using human endothelial cells as a model. The in vivo assay (biodistribution/tissue deposition) has been performed using radiolabeled PLA/PVA NPs.
The nanoparticles produced showed a mean diameter of about 259 nm with a spherical shape. The in-vitro photodynamic therapy tests demonstrated that the combination is critical to enhance the therapeutic efficacy and it is dose dependent. The in vitro cell toxicity assay using endothelial cells demonstrated that the drug encapsulated into nanoparticles had no significant toxicity compared to control samples. In-vivo results demonstrated that the drug loading affects the biodistribution of the nanoparticle formulations (NPs). Low accumulation of the NPs into the stomach, heart, brain, and kidneys suggested that common side effects of Dacarbazine could be reduced.
This work reports a robust nanoparticle formulation with the objective to leveraging the synergistic effects of chemo and photodynamic therapies to potentially suppressing the drug resistance and reducing side effects associated with Dacarbazine. The data corroborates that the dual encapsulated NPs showed better in-vitro efficacy when compared with the both compounds alone. The results support the need to have a dual modality NP formulation for melanoma therapy by combining chemotherapy and photodynamic therapy.
黑色素瘤是一种侵袭性很强的皮肤癌，具有多药耐药性，导致患者生存率较低。因此，需要测试新的治疗方法，以提高治疗效果并减少传统治疗的副作用。
采用双乳液技术制备了负载达卡巴嗪和酞菁锌的聚乳酸/聚乙烯醇纳米颗粒。通过动态光散射和原子力显微镜进行表征。以MV3黑色素瘤细胞为模型进行了体外光动力治疗测试分析。以人内皮细胞为模型，进行体外细胞活力（MTT）测定，以测量含药和不含药纳米颗粒的细胞毒性。使用放射性标记的聚乳酸/聚乙烯醇纳米颗粒进行了体内分析（生物分布/组织沉积）。
制备的纳米颗粒平均直径约为259nm，呈球形。体外光动力治疗测试表明，这种组合对于提高治疗效果至关重要，且具有剂量依赖性。使用内皮细胞进行的体外细胞毒性测定表明，与对照样品相比，封装在纳米颗粒中的药物没有明显毒性。体内结果表明，药物负载会影响纳米颗粒制剂（NPs）的生物分布。纳米颗粒在胃、心脏、大脑和肾脏中的低积累表明，达卡巴嗪的常见副作用可能会减少。
本研究报告了一种强大的纳米颗粒制剂，旨在利用化疗和光动力疗法的协同作用，潜在地抑制耐药性并减少与达卡巴嗪相关的副作用。数据证实，与单独使用两种化合物相比，双重封装的纳米颗粒在体外显示出更好的疗效。结果支持了通过联合化疗和光动力疗法制备用于黑色素瘤治疗的双模态纳米颗粒制剂的必要性。
