Assessment of Intracellular Delivery Potential of Novel Sustainable Poly(δ-decalactone)-Based Micelles
Assessment of Intracellular Delivery Potential of Novel Sustainable Poly(δ-decalactone)-Based Micelles
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DOI：
10.3390/pharmaceutics12080726
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发表时间：
2020-08-01
期刊：
影响因子：
5.4
通讯作者：
Rosenholm, Jessica M.
中科院分区：
文献类型：
--
作者：
Bansal, Kuldeep Kumar;Ozliseli, Ezgi;Rosenholm, Jessica M.
近年来，来自可再生资源的生物可降解聚合物在生物医学领域引起了广泛关注。最近，基于聚（δ-癸内酯）的共聚物胶束已经作为潜在的药物递送载体材料作为化石基聚合物的可持续替代品而出现。然而，他们的细胞内药物输送潜力尚未调查，因此，在这项工作中，我们报告的合成和细胞摄取效率的聚（δ-癸内酯）为基础的胶束有或没有一个靶向配体。选择叶酸作为模型靶向配体，罗丹明B作为荧光示踪剂，以证明共聚物的直接官能化方面。嵌段共聚物的合成是通过简单的开环聚合和点击化学的组合来完成的，以保持结构的均匀性。在直径类似于150 nm的胶束表面上存在叶酸使叶酸受体过表达的MDA-MB-231细胞上的摄取效率提高了1.6倍，表明利用配体功能实现了靶向。通过使用多西他赛作为模型药物来确定这些载体的药物递送能力，其中药物的体外细胞毒性在孵育后48 h掺入胶束中后显著增加。我们还研究了非靶向胶束可能的内吞途径，发现小窝介导的内吞是首选的摄取途径。本工作加强了使用新型生物基聚（δ-癸内酯）胶束作为有效的多功能药物递送纳米载体对医疗应用的前景。
Biodegradable polymers from renewable resources have attracted much attention in recent years within the biomedical field. Lately, poly(delta-decalactone) based copolymer micelles have emerged as a potential drug delivery carrier material as a sustainable alternative to fossil-based polymers. However, their intracellular drug delivery potential is not yet investigated and therefore, in this work, we report on the synthesis and cellular uptake efficiency of poly(delta-decalactone) based micelles with or without a targeting ligand. Folic acid was chosen as a model targeting ligand and Rhodamine B as a fluorescent tracer to demonstrate the straightforward functionalisation aspect of copolymers. The synthesis of block copolymers was accomplished by a combination of facile ring-opening polymerisation and click chemistry to retain the structure uniformity. The presence of folic acid on the surface of micelles with diameter similar to 150 nm upsurge the uptake efficiency by 1.6 fold on folate receptor overexpressing MDA-MB-231 cells indicating the attainment of targeting using ligand functionality. The drug delivery capability of these carriers was ascertained by using docetaxel as a model drug, whereby the in vitro cytotoxicity of the drug was significantly increased after incorporation in micelles 48 h post incubation. We have also investigated the possible endocytosis route of non-targeted micelles and found that caveolae-mediated endocytosis was the preferred route of uptake. This work strengthens the prospect of using novel bio-based poly(delta-decalactone) micelles as efficient multifunctional drug delivery nanocarriers towards medical applications.