Abstract:
Breast cancer treatment can be challenging, but a targeted drug delivery system (DDS) has the potential to make it more effective and reduce side effects. This study presents a novel nanotherapeutic targeted DDS developed through the self-assembly of an amphiphilic di-block copolymer to deliver the chemotherapy drug SN38 specifically to breast cancer cells. The vehicle was constructed from the PHPMA-b-PEAMA diblock copolymer synthesized via RAFT polymerization. A single emulsion method was then used to encapsulate SN38 within nanoparticles (NPs) formed from the PHPMA-b-PEAMA copolymer. The AS1411 DNA aptamer was covalently bonded to the surface of the micellar NPs, producing a targeted DDS. Molecular dynamics (MD) simulation studies were also performed on the di block polymeric system, demonstrating that SN38 interacted well with the di block. The in vitro results demonstrated that AS1411- decorated SN38-loaded HPMA NPs were highly toxic to breast cancer cells while having a minimal effect on non-cancerous cells. Remarkably, in vivo studies elucidated the ability of the targeted DDS to enhance the antitumor effect of SN38, suppressing tumor growth and improving survival rates compared to free SN38.
摘要:
乳腺癌治疗具有挑战性,但是靶向给药系统(DDS)有可能使其更有效并减少副作用。这项研究提出了一种通过两亲性二嵌段共聚物的自组装开发的新型纳米治疗靶向DDS,以将化疗药物SN38特异性地递送至乳腺癌细胞。载体由通过RAFT聚合合成的PHPMA-b-PEAMA二嵌段共聚物构成。然后使用单乳液方法将SN38包封在由PHPMA-b-PEAMA共聚物形成的纳米颗粒(NP)内。AS1411DNA适体共价结合到胶束NP的表面,产生目标DDS。还对二嵌段聚合物体系进行了分子动力学(MD)模拟研究,证明SN38与di区块相互作用良好。体外结果表明,AS1411修饰的SN38负载的HPMANP对乳腺癌细胞具有高毒性,而对非癌细胞的影响最小。值得注意的是,体内研究阐明了与游离SN38相比,靶向DDS增强SN38的抗肿瘤作用、抑制肿瘤生长和提高存活率的能力。