Design and synthesis of a star-like polymeric micelle modified with AS1411 aptamer for targeted delivery of camptothecin for cancer therapy.

Abstract

Improving of tumor targeting and decreasing side effects at normal cells of antitumor drugs are necessary to promote the cancer chemotherapy efficacy. Herein, we have synthesized a novel 21-arm star like diblock polymer of β-cyclodextrin-{poly(ε-caprolactone)-poly(2-aminoethylmethacrylate)}21 which decorated with nucleolin aptamer (AS1411). The diblock polymer was prepared by combined ROP with electron transfer atom transfer radical polymerization (ARGET ATRP) methods followed camptothecin (CPT) encapsulation with high entrapment efficiency (65%). Subsequently, the attachment of AS1411 aptamer via covalent bond led to the formation of the final product β-CD-(PCL-PAEMA)21/AS1411/CPT. In vitro drug release experiment demonstrated almost 50% of CPT was released in 72 h at acidic tumoral environment. The data of cellular toxicity (MTT) showed that the final product remarkably enhanced cell death in MCF-7 and 4T1 cells while normal cells (L929) showed high viability toward the prepared complex. Also, the finding of flow cytometry analysis and fluorescence imaging indicated successful internalization of complex into the target cells but not the nontarget cells. The in vivo experiments revealed the fact that β-CD-(PCL-PAEMA)21/AS1411/CPT micelles showed high tumor inhibitory potential in comparison with free CPT. These findings exhibited the excellent ability of the novel star-like polymeric micelle with targeting agent for the targeted and effective delivery of CPT in cancer treatment.

• Authors: Atena Jabbari, Elnaz Yaghoobi, Hamid Azizollahi, Saeed Shojaee, Mohammad Ramezani, Mona Alibolandi, Khalil Abnous, Seyed Mohammad Taghdisi
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 611 Pg. 121346 (Jan 05 2022) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 34871712 (Publication Type: Journal Article)
• Copyright: Copyright © 2021. Published by Elsevier B.V.

Chemical References

• AGRO 100
• Aptamers, Nucleotide
• Micelles
• Oligodeoxyribonucleotides
• Polymers
• Camptothecin

Topics

• Aptamers, Nucleotide
• Camptothecin
• Micelles
• Neoplasms (drug therapy)
• Oligodeoxyribonucleotides
• Polymers