多西他赛 (DTX) 是转移性前列腺癌 (PCa) 患者的推荐治疗方法，尽管其治疗效果因强烈的全身毒性而受到限制。然而，在局部 PCa 中，瘤内 (IT) 给予 DTX 可能是一种替代方案，有助于克服传统静脉 (IV) 治疗的缺点。在此背景下，我们在这里提出了第一个体内临床前研究，通过IT注射对带有人类前列腺腺癌肿瘤的异种移植小鼠模型使用介孔二氧化硅纳米颗粒（MSN）和DTX的纳米药物治疗PCa。研究了DTX纳米药物和游离药物的疗效和耐受性、治疗后的生物分布和组织病理学，并与DTX静脉注射进行比较。所得结果表明，IT 注射 DTX 和 DTX 纳米药物可以精确、选择性地治疗非转移性前列腺癌，并最大限度地减少药物的全身扩散，显示出比静脉注射途径更优异的活性。这使得治疗剂量减少了一个数量级，并大大拓宽了该药物的治疗窗口。此外，使用 DTX 纳米药物作为 IT 注射剂可促进强大的抗肿瘤功效和肿瘤部位的药物积累，从而改善通过相同途径使用游离药物获得的结果。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

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.Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.