基因疗法已成为治疗癌症的一种有前景的途径，具有对目标基因进行有意调整的优势。尽管如此，血液中核酸的快速降解需要有效且安全的输送系统。聚乳酸-乙醇酸 (PLGA) 纳米颗粒作为药物输送系统的广泛应用凸显了控制颗粒尺寸和释放特性方面的挑战。此外，由于 PLGA 纳米粒子表面带负电，核酸的封装加剧了这些困难。在这项研究中，我们旨在通过使用带负电的微珠并优化特定配制步骤的时间安排来提高核酸的封装效率。此外，通过将前列腺特异性膜抗原 (PSMA) 的配体 PSMA-617 与 PLGA 纳米颗粒结合，我们评估了核酸递送系统对前列腺癌模型的抗肿瘤作用和功效。核酸封装系统中所采用的技术代表了一种可适用于封装各种核酸的新颖方法。此外，它能够将靶向部分附着到不同的细胞膜蛋白上，从而揭示癌症治疗中精确疗法的新前景。© 2024 作者。

Gene therapy has surfaced as a promising avenue for treating cancers, offering the advantage of deliberate adjustment of targeted genes. Nonetheless, the swift degradation of nucleic acids in the bloodstream necessitates an effective and secure delivery system. The widespread utilization of poly(lactic-co-glycolic acid) (PLGA) nanoparticles as drug delivery systems has highlighted challenges in controlling particle size and release properties. Moreover, the encapsulation of nucleic acids exacerbates these difficulties due to the negatively charged surface of PLGA nanoparticles. In this study, we aimed to improve the encapsulation efficiency of nucleic acids by employing negatively charged microbeads and optimizing the timing of the specific formulation steps. Furthermore, by conjugating PSMA-617, a ligand for the prostate-specific membrane antigen (PSMA), with PLGA nanoparticles, we assessed the antitumor effects and the efficacy of a nucleic acid delivery system on a prostate cancer model. The employed technique within the nucleic acid encapsulation system represents a novel approach that could be adapted to encapsulate various kinds of nucleic acids. Moreover, it enables the attachment of targeting moieties to different cell membrane proteins, thereby unveiling new prospects for precise therapeutics in cancer therapy.© 2024 The Author(s).