Barrios-Esteban Sheila, Alcalde Ignacio, Chacón Manuel, Merayo-Lloves Jesús, de la Fuente María, Csaba Noemi
Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela, Campus Vida, Santiago de Compostela, 15706, Spain.
Fundación de Investigación Oftalmológica, Instituto Universitario Fernández-Vega, University of Oviedo, Oviedo, 33012, Spain.
Drug Deliv Transl Res. 2025 Apr 11. doi: 10.1007/s13346-025-01849-1.
Uveal melanoma is the most common primary intraocular tumor in adults that appears mainly in the choroid, ciliary body, or iris. Standard non-surgical treatment consists of radiotherapy and chemotherapy by intravitreal injection of drugs, which is hampered by unpleasant side effects and high recurrence rate. As an alternative strategy, gene therapy has the capacity of targeting specific pathways in cancer cells by introducing tumor suppressor sequences that are rendered therapeutically effective by the use of suitable delivery vectors. In this paper, we describe the development of protamine nanocapsules as potential gene delivery carriers to the eye by its topical administration. These nanocapsules, composed of spherical oily nano-droplets surrounded by a protamine shell with small particle size (≤ 250 nm) and positive surface charge (+ 33 mV), can efficiently associate different nucleic acids such as pDNA and miRNA, and release them in biorelevant media. In vitro studies evidenced their low cytotoxicity and efficient internalization with 36% of TAMRA-positive cells, and transfection capacity from doses of 0.5 µg of pDNA in uveal melanoma cells. Finally, the results also confirmed their efficient interaction and permeation in primary patient-derived 3D corneal models with a reduction of up to 60% in TEER values, without altering the structure of this ocular barrier.
葡萄膜黑色素瘤是成人中最常见的原发性眼内肿瘤，主要出现在脉络膜、睫状体或虹膜。标准的非手术治疗包括放疗和通过玻璃体内注射药物进行化疗，但存在不良反应和高复发率的问题。作为一种替代策略，基因治疗能够通过引入肿瘤抑制序列来靶向癌细胞中的特定途径，这些序列通过使用合适的递送载体而具有治疗效果。在本文中，我们描述了通过局部给药将鱼精蛋白纳米胶囊作为潜在的基因递送载体用于眼部的研究进展。这些纳米胶囊由球形油性纳米液滴组成，周围包裹着鱼精蛋白外壳，粒径小（≤250nm）且表面带正电荷（+33mV），能够有效地结合不同的核酸，如质粒DNA（pDNA）和微小RNA（miRNA），并在生物相关介质中释放它们。体外研究证明了它们的低细胞毒性和高效内化，TAMRA阳性细胞占36%，并且在葡萄膜黑色素瘤细胞中，从0.5μg pDNA的剂量开始就具有转染能力。最后，结果还证实了它们在原发性患者来源的3D角膜模型中的有效相互作用和渗透，跨上皮电阻（TEER）值降低高达60%，而不会改变这种眼部屏障的结构。
