"In vitro" behaviour of aptamer-functionalized polymeric nanocapsules loaded with 5-fluorouracil for targeted therapy
"In vitro" behaviour of aptamer-functionalized polymeric nanocapsules loaded with 5-fluorouracil for targeted therapy
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DOI：
10.1016/j.msec.2019.109828
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发表时间：
2019-10-01
影响因子：
7.9
通讯作者：
Popa, Marcel
中科院分区：
文献类型：
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作者：
Rata, Delia Mihaela;Cadinoiu, Anca Niculina;Popa, Marcel
开发了基于用 AS1411 适体功能化的羧甲基壳聚糖和负载 5-氟尿嘧啶 (5-FU) 的聚（N-乙烯基吡咯烷酮-alt-衣康酸酐）的新型纳米胶囊，具有改善癌症治疗的潜力。由于与核仁素的相互作用以及随后的内吞作用，具有 AS1411 适体的纳米胶囊的功能化将增强肿瘤细胞对它们的识别。在不使用任何有毒交联剂的情况下，通过界面缩合法制备纳米胶囊。在壳聚糖/适体官能化羧甲基壳聚糖混合物的NH 2 基团的作用下，通过打开共聚物的酸酐循环，在有机相和水相之间的界面发生缩合反应。纳米胶囊的直径在 100 至 267 nm 之间变化，作为聚合物摩尔比的函数。 SEM 图像显示纳米胶囊呈球形并具有相对较低的维度多分散性。纳米胶囊在 PBS 溶液（pH = 7.4）中的溶胀度在 1000% 至 1680% 之间，并且它们允许封装大量的 5-氟尿嘧啶 (5-FU)。研究了 5-FU 的释放效率，该过程由药物通过聚合物膜的扩散控制，这已通过药物释放的理论分析得到证实。对纳米胶囊进行的细胞毒性和溶血测试证明其无毒性且具有优异的血液相容性。获得的结果令人鼓舞，表明这些原始的负载5-FU的纳米胶囊能够对肿瘤性MCF-7细胞产生更明显的细胞毒性作用，死细胞的出现比游离5-FU的情况更快。
New type of nanocapsules based on carboxymethyl chitosan functionalized with AS1411 aptamer and poly(N-vinylpyrrolidone-alt-itaconic anhydride) loaded with 5-Fluorouracil (5-FU) were developed, with the potential to improve the treatment of cancer. Functionalization of nanocapsules with AS1411 aptamer will enhance their recognition by tumor cells, due to the interaction with nucleolin, and subsequent endocytosis. Nanocapsules were prepared by interfacial condensation method in the absence of any toxic crosslinking agents. The condensation reaction took place at the interface between the organic and aqueous phases by opening the anhydride cycles from the copolymer, under the action of the NH2 groups from mixture of chitosan/aptamer-functionalized carboxymethyl chitosan. The nanocapsules diameter varied between 100 and 267 nm as a function of the molar ratio of the polymers. SEM images have revealed that nanocapsules were spherical and presented relatively low dimensional polydispersity. Nanocapsules swelling degree was found between 1000 and 1680% in PBS solution (pH = 7.4) and they allowed the encapsulation of an important amount of 5-Fluorouracil (5-FU). The release efficiency of 5-FU was studied, the processes being controlled by the drug diffusion through the polymeric membrane, as confirmed by the theoretical analysis of the drug release. The cytotoxicity and haemolysis tests performed on the nanocapsules proved their lack of toxicity and their excellent hemocompatibility. The obtained results were encouraging, showing that these original 5-FU-loaded nanocapsules were able to induce a more pronounced cytotoxic effect on neoplastic MCF-7 cells, the occurrence of dead cells being more rapidly than in the case of free 5-FU.