Biodegradable polymers from renewable resources have attracted much attention in recent years within the biomedical field. Lately, poly(δ-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(δ-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 ~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(δ-decalactone) micelles as efficient multifunctional drug delivery nanocarriers towards medical applications.

中文翻译：

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新型可持续的聚（δ-癸内酯）胶束的细胞内传递潜力的评估。

来自可再生资源的可生物降解的聚合物近年来在生物医学领域引起了很多关注。近来，基于聚（δ-癸内酯）的共聚物胶束已经成为潜在的药物递送载体材料，可以替代基于化石的聚合物。但是，它们的细胞内药物传递潜力尚未得到研究，因此，在这项工作中，我们报道了有或没有靶向配体的基于聚（δ-癸内酯）的胶束的合成和细胞摄取效率。选择叶酸作为靶向配体的模型，并选择若丹明B作为荧光示踪剂，以证明共聚物的直接官能化方面。嵌段共聚物的合成通过容易的开环聚合和点击化学的结合来完成，以保持结构均匀性。叶酸在直径约150 nm的胶束表面上的存在使过表达叶酸受体的MDA-MB-231细胞的吸收效率提高了1.6倍，这表明使用配体功能实现了靶向。通过使用多西紫杉醇作为模型药物来确定这些载体的药物递送能力，由此在孵育48小时后将其掺入胶束中后，药物的体外细胞毒性显着增加。我们还研究了非靶向胶束的内吞途径，发现小窝介导的内吞作用是首选的摄取途径。这项工作加强了使用新型生物基聚（δ-十内酯）胶束作为面向医学应用的高效多功能药物递送纳米载体的前景。