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通过磁铁矿纳米生物共轭物增强化疗药物在黑色素瘤治疗中的递送和效力。

Enhanced Delivery and Potency of Chemotherapeutics in Melanoma Treatment via Magnetite Nanobioconjugates.

作者信息

Díaz Erika, Quezada Valentina, Cifuentes Javier, Arias Morales Nydia Yadira, Reyes Luis H, Muñoz-Camargo Carolina, Cruz Juan C

机构信息

Department of Biomedical Engineering, Universidad de Los Andes, Bogotá 111711, Colombia.

Center for Microscopy (MicroCore), Vice Presidency for Research and Creation, Universidad de Los Andes, Bogotá 111711, Colombia.

出版信息

ACS Omega. 2024 Oct 30;9(45):45402-45420. doi: 10.1021/acsomega.4c07415. eCollection 2024 Nov 12.

Abstract

Melanoma, known for its aggressive metastatic potential, poses significant treatment challenges. Despite the potent antiproliferative effects of anticancer drugs, systemic toxicity and low water solubility limit their efficacy. This study addresses these challenges by employing magnetite (FeO) nanobioconjugates as a drug delivery system, aimed at enhancing drug solubility and reducing off-target effects in melanoma therapy. Magnetite nanoparticles (MNPs) were engineered with functional molecules and loaded with the anticancer agents Temozolomide (TMZ) or paclitaxel (PTX). The nanobioconjugates were characterized via Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), dynamic light scattering (DLS), and transmission electron microscopy (TEM). The results validated the efficacious synthesis and drug loading, attaining efficiencies ranging from 32 to 72% for TMZ and 32 to 60% for PTX. Biocompatibility assessments demonstrated excellent tolerance, with minimal hemolysis rates and platelet aggregation. In vitro studies revealed enhanced cytotoxicity against A-375 human melanoma cells compared to free drugs, with cellular uptake facilitated primarily through macropinocytosis, caveolin-, and clathrin-mediated endocytosis. Furthermore, the nanobioconjugates exhibited significant efficacy in targeting A-375 melanoma spheroids, underlining their potential in melanoma therapy. This research underscores magnetite nanobioconjugates as a promising avenue for targeted melanoma treatment, offering enhanced drug delivery specificity and reduced systemic toxicity in oncological drug delivery systems.

摘要

黑色素瘤以其具有侵袭性的转移潜能而闻名,带来了重大的治疗挑战。尽管抗癌药物具有强大的抗增殖作用,但全身毒性和低水溶性限制了它们的疗效。本研究通过采用磁铁矿(FeO)纳米生物共轭物作为药物递送系统来应对这些挑战,旨在提高药物溶解度并减少黑色素瘤治疗中的脱靶效应。用功能分子对磁铁矿纳米颗粒(MNP)进行工程改造,并负载抗癌药物替莫唑胺(TMZ)或紫杉醇(PTX)。通过傅里叶变换红外光谱(FTIR)、热重分析(TGA)、动态光散射(DLS)和透射电子显微镜(TEM)对纳米生物共轭物进行表征。结果验证了有效的合成和药物负载,TMZ的负载效率为32%至72%,PTX的负载效率为32%至60%。生物相容性评估显示出极佳的耐受性,溶血率和血小板聚集率极低。体外研究表明,与游离药物相比,纳米生物共轭物对A-375人黑色素瘤细胞的细胞毒性增强,细胞摄取主要通过巨胞饮作用、小窝蛋白介导的内吞作用和网格蛋白介导的内吞作用来促进。此外,纳米生物共轭物在靶向A-375黑色素瘤球体方面表现出显著疗效,突显了它们在黑色素瘤治疗中的潜力。本研究强调磁铁矿纳米生物共轭物是靶向治疗黑色素瘤的一个有前景的途径,在肿瘤药物递送系统中提供了更高的药物递送特异性并降低了全身毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db71/11561594/9b880563de99/ao4c07415_0001.jpg

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