雄激素受体集成溶解微针的 PROTAC 降解剂通过单一局部给药用于雄激素性脱发和复发治疗,Small Methods

当前位置： X-MOL 学术 › Small Methods › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

雄激素受体集成溶解微针的 PROTAC 降解剂通过单一局部给药用于雄激素性脱发和复发治疗
Small Methods ( IF 10.7 ) Pub Date : 2022-12-20 , DOI: 10.1002/smtd.202201293
Ruxuan Wang ₁ , Tengjiang Zhong _{2,

3} , Qiong Bian _{1,

4} , Sai Zhang _{2,

3} , Xiaolu Ma ₁ , Liming Li ₅ , Yihua Xu ₁ , Yueting Gu ₁ , Anran Yuan ₁ , Weitong Hu ₁ , Chong Qin _{2,

3} , Jianqing Gao _{1,

6}

Affiliation

雄激素性脱发（AGA）是一种全球范围内跨种族、跨性别的疾病，具有年轻化倾向，但缺乏有效的治疗方法。雄激素受体(androgen receptor, AR)与雄激素的结合在AGA的发生、发展过程中起着至关重要的作用。在此，合成了新型蛋白水解靶向 AR 嵌合体降解剂 (AR-PROTAC) 并与溶解微针 (PROTAC-MNs) 整合，以实现毛囊中的 AR 破坏，用于 AGA 治疗。PROTAC-MNs 具有足够的机械能力，可以将 AR-PROTAC 精确地输送到毛囊所在区域以进行 AR 降解。与每天使用一线外用药物米诺地尔相比，PROTAC-MNs 仅局部使用一次后，毛发再生开始加速。有趣的是，通过单次给药的 PROTAC-MNs 在 AGA 复发中仍然实现了优异的毛发再生，这是米诺地尔在临床实践中的主要缺点。随着 AR 的降解，PROTAC-MNs 成功地调节了与头发生长相关的信号级联并激活了毛囊干细胞。此外，PROTAC-MNs 不会在体内引起全身毒性或雄激素缺乏相关的混乱。总的来说，这些具有持久疗效、一步给药和高生物相容性的 AR 降解溶解微针为 AGA 治疗提供了巨大的治疗潜力。PROTAC-MNs 成功地调节了与头发生长相关的信号级联并激活了毛囊干细胞。此外，PROTAC-MNs 不会在体内引起全身毒性或雄激素缺乏相关的混乱。总的来说，这些具有持久疗效、一步给药和高生物相容性的 AR 降解溶解微针为 AGA 治疗提供了巨大的治疗潜力。PROTAC-MNs 成功地调节了与头发生长相关的信号级联并激活了毛囊干细胞。此外，PROTAC-MNs 不会在体内引起全身毒性或雄激素缺乏相关的混乱。总的来说，这些具有持久疗效、一步给药和高生物相容性的 AR 降解溶解微针为 AGA 治疗提供了巨大的治疗潜力。

"点击查看英文标题和摘要"

PROTAC Degraders of Androgen Receptor-Integrated Dissolving Microneedles for Androgenetic Alopecia and Recrudescence Treatment via Single Topical Administration

Androgenetic alopecia (AGA) is a transracial and cross-gender disease worldwide with a youth-oriented tendency, but it lacks effective treatment. The binding of androgen receptor (AR) and androgen plays an essential role in the occurrence and progression of AGA. Herein, novel proteolysis targeting chimera degrader of AR (AR-PROTAC) is synthesized and integrated with dissolving microneedles (PROTAC-MNs) to achieve AR destruction in hair follicles for AGA treatment. The PROTAC-MNs possess adequate mechanical capabilities for precise AR-PROTAC delivery into the hair follicle-residing regions for AR degradation. After applying only once topically, the PROTAC-MNs achieve an accelerated onset of hair regeneration as compared to the daily application of the first-line topical drug minoxidil. Intriguingly, PROTAC-MNs via single administration still realize superior hair regeneration in AGA recrudescence, which is the major drawback of minoxidil in clinical practice. With the degradation of AR, the PROTAC-MNs successfully regulate the signaling cascade related to hair growth and activate hair follicle stem cells. Furthermore, the PROTAC-MNs do not cause systemic toxicity or androgen deficiency-related chaos in vivo. Collectively, these AR-degrading dissolving microneedles with long-lasting efficacy, one-step administration, and high biocompatibility provide a great therapeutic potential for AGA treatment.

更新日期：2022-12-20

点击分享查看原文

点击收藏

阅读更多本刊新发论文