Transdermal siRNA delivery by pH-switchable micelles with targeting effect suppress skin melanoma progression.,Journal of Controlled Release

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Transdermal siRNA delivery by pH-switchable micelles with targeting effect suppress skin melanoma progression.
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2020-03-17 , DOI: 10.1016/j.jconrel.2020.03.023
Mao-Ze Wang ₁ , Jie Niu ₁ , Hui-Jian Ma ₁ , Haseeb Anwar Dad ₁ , Hai-Tao Shao ₁ , Tie-Jun Yuan ₁ , Li-Hua Peng ₂

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Melanoma is an aggressive disease with rapid progression and fast relapse, representing one of the formidable challenges in clinic. Current systemic therapies for melanoma exhibit limited anticancer potential due to the lack of specificity and limited efficacy. Herein, we design a cationic polymer (SCP-HA-PAE) by conjugating skin/cell penetrating peptide (SCP) and hyaluronic acid (HA) to the amphipathic polymer (poly β-amino esters, PAE), then fabricate the nanocarriers (SHP) composed by SCP-HA-PAE for delivering siRNA to skin melanoma by transdermal application. SHP not only manifests the excellent ability in penetrating through skin stratum corneum (SC), targeting melanoma and being sensitive to pH, but also expresses the advantages in compacting the vector/siRNAs nanocomplexes and stimulating their endosome escape inside cells, which ensure the enhanced siRNA delivery efficiency. SHP/siRNA induce the strong efficacy in retarding the progression and relapse of skin melanoma through the enhanced apoptosis effect both in vitro & in vivo. This study provides a proof-of-concept design of pH-switchable cationic micelles as transdermal gene delivery nanoplatforms with targeting effect for melanoma therapy, which may be adapted widely in the treatment of various superficial tumors and skin genetic diseases.

中文翻译：

pH调节胶束具有靶向作用的透皮siRNA传递抑制了皮肤黑色素瘤的进展。

黑色素瘤是一种具有快速发展和快速复发的侵袭性疾病，代表了临床上的巨大挑战之一。由于缺乏特异性和有限的疗效，目前用于黑素瘤的全身疗法显示出有限的抗癌潜力。本文中，我们通过将皮肤/细胞穿透肽（SCP）和透明质酸（HA）与两亲性聚合物（聚β-氨基酯，PAE）结合来设计阳离子聚合物（SCP-HA-PAE），然后制造纳米载体（SHP）由SCP-HA-PAE组成，可通过经皮应用将siRNA传递至皮肤黑色素瘤。SHP不仅表现出出色的穿透角质层（SC），靶向黑色素瘤和对pH敏感的能力，而且还表现出了压实载体/ siRNA纳米复合物并刺激其内体逃逸到细胞内的优势，这确保了增强的siRNA输送效率。SHP / siRNA通过增强体内和体外的细胞凋亡作用，在延缓皮肤黑素瘤的进展和复发方面具有强大的功效。这项研究提供了可pH调节的阳离子胶束作为具有靶向作用的黑色素瘤治疗的透皮基因传递纳米平台的概念验证设计，可广泛应用于治疗各种浅表性肿瘤和皮肤遗传病。

更新日期：2020-03-19

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