Instituto de Tecnología Química (UPV-CSIC), Universitat Politècnica de València-Consejo Superior de Investigaciones Científicas, Avda. de los Naranjos s/n, 46022 València, Spain.
Escuela de Doctorado, Universidad Católica de Valencia, Plaza de San Agustín 3, 46001 Valencia, Spain; Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell, 106, 46026 Valencia, Spain.
Int J Pharm. 2024 Oct 25;664:124623. doi: 10.1016/j.ijpharm.2024.124623. Epub 2024 Aug 25.
Docetaxel (DTX) is a recommended treatment in patients with metastasic prostate cancer (PCa), despite its therapeutic efficacy is limited by strong systemic toxicity. However, in localized PCa, intratumoral (IT) administration of DTX could be an alternative to consider that may help to overcome the disadvantages of conventional intravenous (IV) therapy. In this context, we here present the first in vivo preclinical study of PCa therapy with nanomedicines of mesoporous silica nanoparticles (MSN) and DTX by IT injection over a xenograft mouse model bearing human prostate adenocarcinoma tumors. The efficacy and tolerability, the biodistribution and the histopathology after therapy have been investigated for the DTX nanomedicine and the free drug, and compared with the IV administration of DTX. The obtained results demonstrate that IT injection of DTX and DTX nanomedicines allows precise and selective therapy of non-metastatic PCa and minimize systemic diffusion of the drug, showing superior activity than IV route. This allows reducing the therapeutic dose by one order and widens substantially the therapeutic window for this drug. Furthermore, the use of DTX nanomedicines as IT injection promotes strong antitumor efficacy and drug accumulation at the tumor site, improving the results obtained with the free drug by the same route.
多西他赛（DTX）是转移性前列腺癌（PCa）患者的推荐治疗方法，尽管其治疗效果受到强烈的全身毒性限制。然而，在局限性 PCa 中，肿瘤内（IT）给予 DTX 可能是一种替代方法，可以帮助克服常规静脉内（IV）治疗的缺点。在这方面，我们在这里介绍了第一个用介孔硅纳米粒子（MSN）和 IT 注射的 DTX 纳米药物治疗前列腺癌的体内临床前研究，该研究在携带人前列腺腺癌肿瘤的异种移植小鼠模型中进行。对 DTX 纳米药物和游离药物的疗效和耐受性、生物分布和治疗后的组织病理学进行了研究，并与 IV 给予 DTX 进行了比较。结果表明，IT 注射 DTX 和 DTX 纳米药物可实现非转移性 PCa 的精确和选择性治疗，并最大限度地减少药物的全身扩散，其活性优于 IV 途径。这允许将治疗剂量降低一个数量级，并大大扩大该药物的治疗窗口。此外，将 DTX 纳米药物作为 IT 注射使用可促进肿瘤部位的强大抗肿瘤疗效和药物积累，通过相同途径改善了游离药物的结果。
