Chitosan-modified PLGA nanoparticles tagged with 5TR1 aptamer for in vivo tumor-targeted drug delivery.

Abstract

In this study, we reported epirubicin (Epi) encapsulated nanoparticles (NPs) formulated with biocompatible and biodegradable poly (lactic-co-glycolic acid) (PLGA) modified with chitosan (CS) through a physical adsorption method. Using chitosan, the solubility and surface charge of PLGA was modified to make efficient drug carriers for cancer cells. To improve the anti-tumor efficacy, we developed targeted therapy of tumor cells using a 5TR1 DNA aptamer (Apt) against the MUC1 receptor. To prove the MUC1 receptor-mediated uptake of Epi-PLGA-CS-Apt NPs in the cells, competition experiments were carried out. In vitro experiments, cytotoxicity assay and fluorescence uptake assay demonstrated that fabricated NPs with or without aptamers showed significantly high therapeutic efficiency in MCF7 cells (breast cancer cell) compared with free Epi, while in BALB/c mice bearing C26 cells (murine colon carcinoma cell), targeted NP groups exhibited significant tumor growth inhibition and higher inclination to tumor compared with non-targeted NPs. Hence, our in vivo results revealed that non-targeted NPs may diffuse away from the tumor site and release Epi in the extracellular space and decrease concentration of the drug in the targeted tissue. This study indicated Epi-PLGA-CS-Apt has great potential as a promising nanoplatform for in vivo cancer therapy and could be of great value in medical use.

• Authors: Sahar Taghavi, Mohammad Ramezani, Mona Alibolandi, Khalil Abnous, Seyed Mohammad Taghdisi
• Journal: Cancer letters (Cancer Lett) Vol. 400 Pg. 1-8 (08 01 2017) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 28412238 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• 5TR1 aptamer
• Antibiotics, Antineoplastic
• Aptamers, Nucleotide
• Drug Carriers
• Mucin-1
• muc1 protein, mouse
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid
• Epirubicin
• Chitosan

Topics

• Adsorption
• Animals
• Antibiotics, Antineoplastic (administration & dosage, chemistry)
• Aptamers, Nucleotide (administration & dosage, chemistry, genetics, metabolism)
• CHO Cells
• Cell Survival (drug effects)
• Chitosan (analogs & derivatives, chemistry)
• Colonic Neoplasms (drug therapy, genetics, metabolism, pathology)
• Cricetulus
• Drug Carriers
• Drug Compounding
• Drug Liberation
• Epirubicin (administration & dosage, chemistry)
• Female
• Humans
• Lactic Acid (chemistry)
• MCF-7 Cells
• Mice, Inbred BALB C
• Mucin-1 (genetics, metabolism)
• Nanomedicine
• Nanoparticles
• Polyglycolic Acid (chemistry)
• Polylactic Acid-Polyglycolic Acid Copolymer
• Solubility
• Surface Properties
• Technology, Pharmaceutical (methods)
• Time Factors
• Tumor Burden (drug effects)