“In vitro” behaviour of aptamer-functionalized polymeric nanocapsules loaded with 5-fluorouracil for targeted therapy

• Published in: Materials Science & Engineering C 2019-10, Vol.103, p.109828, Article 109828
• Main Authors: Rață, Delia Mihaela, Cadinoiu, Anca Niculina, Atanase, Leonard Ionut, Bacaita, Simona Elena, Mihalache, Cristian, Daraba, Oana-Maria, Gherghel, Daniela, Popa, Marcel
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Anhydrides; Aptamer-functionalized nanocapsules; Aptamers; Aptamers, Nucleotide - chemistry; Aptamers, Nucleotide - pharmacokinetics; Aptamers, Nucleotide - pharmacology; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Chitosan; Condensation; Controlled drug release; Crosslinking; Cytotoxicity; Delayed-Action Preparations - chemistry; Delayed-Action Preparations - pharmacokinetics; Delayed-Action Preparations - pharmacology; Drug delivery systems; Endocytosis; Female; Fluorouracil - chemistry; Fluorouracil - pharmacokinetics; Fluorouracil - pharmacology; Hemocompatibility; Human breast carcinoma; Humans; Materials science; MCF-7 Cells; Nanocapsules - chemistry; Nanocapsules - therapeutic use; Nucleolin; Oligodeoxyribonucleotides - chemistry; Oligodeoxyribonucleotides - pharmacokinetics; Oligodeoxyribonucleotides - pharmacology; Particle Size; Polydispersity; Polymers; Theoretical analysis; Toxicity; Tumor cells; Vinylpyrrolidone
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2019.109828

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. [Display omitted] •Chitosan-based nanocapsules functionalized with AS1411 aptamer, in the range of 100 to 267 nm, were successfully prepared.•5-Fluorouracil release efficiency depends on the morphology and physicochemical characteristics of the nanocapsules.•The aptamer-functionalized nanocapsules show a good compatibility with the bloodstream and do not have a cytotoxic effect.