高度延迟释放的癌症疫苗和免疫调节剂通过双层可降解微针预防治疗转移性癌症。
Highly Prolonged Release of the Cancer Vaccine and Immunomodulator via a Two-Layer Biodegradable Microneedle for Prophylactic Treatment of Metastatic Cancer.
发表日期:2023 Feb 21
作者:
Huu Thuy Trang Duong, Yue Yin, Thai Minh Duy Le, Ji Hoon Jeong, Doo Sung Lee
来源:
BIOMACROMOLECULES
摘要:
同时持续释放癌症疫苗和免疫调节剂,可以有效地触发持久的免疫反应并避免多次给药。我们基于由聚乙二醇(PEG)和聚(磺胺甲噻唑酯脲)(PSMEU)构成的可生物降解共聚物基质,建立了一种生物可降解微针(bMN)。该bMN被应用于皮肤上,并在表皮/真皮层缓慢降解。然后,由一个带正电聚合物(DA3)、癌症DNA疫苗(pOVA)和Toll样受体3激动剂聚(I/C)组成的复合物在无痛的方式下与基质同时释放。整个微针贴片由两层构成。基础层由聚乙烯吡咯烷酮/聚乙烯醇制成,可以在将微针贴片贴于皮肤后迅速溶解,而微针层则由包含可生物降解的PEG-PSMEU的复合物形成,该复合物会在注射部位停留以持续释放治疗剂。根据结果,在体外和体内,10天是复合物完全释放并在抗原提呈细胞中表达特异性抗原的时间。值得注意的是,这个系统可以成功地引起癌症特异性的体液免疫反应,并在单次免疫注射后抑制肺部的转移性肿瘤。
Simultaneous sustained release of cancer vaccines and immunomodulators may effectively trigger durable immune responses and avoid multiple administrations. Here, we established a biodegradable microneedle (bMN) based on a biodegradable copolymer matrix made of polyethylene glycol (PEG) and poly(sulfamethazine ester urethane) (PSMEU). This bMN was applied to the skin and slowly degraded in the epidermis/dermis layers. Then, the complexes composed of a positively charged polymer (DA3), cancer DNA vaccine (pOVA), and toll-like receptor 3 agonist poly(I/C) were synchronously released from the matrix in a pain-free manner. The whole microneedle patch was fabricated with two layers. The basal layer was formed using polyvinyl pyrrolidone/polyvinyl alcohol that could be rapidly dissolved upon applying the microneedle patch to the skin, whereas the microneedle layer was formed by complexes encapsulating biodegradable PEG-PSMEU, which was stuck at the injection site for sustained release of therapeutic agents. According to the results, 10 days is the time for the complexes to be completely released and express specific antigens in antigen-presenting cells in vitro and in vivo. It is noteworthy that this system could successfully elicit cancer-specific humoral immune responses and inhibit metastatic tumors in the lungs after a single shot of immunization.