RT Journal Article T1 Protamine nanocapsules as gene delivery carriers for the treatment of intraocular tumors A1 Barrios Esteban, Sheila A1 Alcalde Domínguez, Ignacio A1 Chacón Rodríguez, Manuel A1 Merayo Lloves, Jesús A1 Fuente Freire, María de la A1 Csaba, Noemi Stefania K1 Gene delivery K1 Protamine nanocapsules K1 Nucleic acids K1 Topical administration K1 Uveal melanoma K1 3D corneal model AB 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. PB Springer SN 2190-393X YR 2025 FD 2025-04-11 LK https://hdl.handle.net/10347/42440 UL https://hdl.handle.net/10347/42440 LA eng NO Barrios-Esteban, S., Alcalde, I., Chacón, M. et al. Protamine nanocapsules as gene delivery carriers for the treatment of intraocular tumors. Drug Deliv. and Transl. Res. (2025). https://doi.org/10.1007/s13346-025-01849-1 NO Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This research was funded by XUNTA DE GALICIA- Consellería de Cultura, Educación e Ordenación Universitaria (Centro singular de investigación de Galicia, accreditation 2019–2022), COMPETITIVE REFERENCE GROUPS (ED431C 2021/17-FEDER), GOBIERNO DE ESPAÑA- Ministerio de Ciencia e Innovación (PID2019- 107500RB-100), and AGENCIA ESTATAL DE INVESTIGACIÓN (PID2019-111745RB-I00), and INSTITUTO DE SALUD CARLOS III (RD21/0002/0041). DS Minerva RD 4 may 2026