Novel Aptamer-Nanoparticle Bioconjugates Enhances Delivery of Anticancer Drug to MUC1-Positive Cancer Cells In Vitro

Chenchen Yu,Jinhong Duan,Chen Wang,Wei Yuan,Haiyan Xu,Xian-Da Yang,Yan Hu,Tarl Wayne Prow

doi:10.1371/journal.pone.0024077

Abstract

MUC1 protein is an attractive target for anticancer drug delivery owing to its overexpression in most adenocarcinomas. In this study, a reported MUC1 protein aptamer is exploited as the targeting agent of a nanoparticle-based drug delivery system. Paclitaxel (PTX) loaded poly (lactic-co-glycolic-acid) (PLGA) nanoparticles were formulated by an emulsion/evaporation method, and MUC1 aptamers (Apt) were conjugated to the particle surface through a DNA spacer. The aptamer conjugated nanoparticles (Apt-NPs) are about 225.3 nm in size with a stable in vitro drug release profile. Using MCF-7 breast cancer cell as a MUC1-overexpressing model, the MUC1 aptamer increased the uptake of nanoparticles into the target cells as measured by flow cytometry. Moreover, the PTX loaded Apt-NPs enhanced in vitro drug delivery and cytotoxicity to MUC1+ cancer cells, as compared with non-targeted nanoparticles that lack the MUC1 aptamer (P<0.01). The behavior of this novel aptamer-nanoparticle bioconjugates suggests that MUC1 aptamers may have application potential in targeted drug delivery towards MUC1-overexpressing tumors.

Highlights

Chemotherapy is a primary treatment for cancer, but its efficacy is often limited due to associated adverse effects
We report that the MUC1 aptamernanoparticle enhances the delivery of anticancer drug to MUC1positive MCF-7 cells in vitro
To conjugate the aptamer-spacer complex to PTX-loaded NPs, ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and NHS were added to catalyze the formation of covalent couple between the -COOH of PLGA on the nanoparticle surface and the 39-NH2 MUC1 aptamer (Fig. 1B)

Summary

Introduction

Chemotherapy is a primary treatment for cancer, but its efficacy is often limited due to associated adverse effects. Nanoparticle (NP) has been proved of great potential for drug delivery due to the passive tumor-targeting effect of enhanced permeability and retention (EPR) exhibited by most nano-carriers [1]. Aptamers are small strands of DNA or RNA that could form unique 3-dimensional structures that combine to molecular targets with high affinity. Comparing to other targeting agents, aptamers possess distinctive advantages: low synthesis cost, low-immunogenicity, small size that makes it easy to penetrate through solid tumors, and high affinity comparable to monoclonal antibodies for binding to almost any molecules. Aptamers have been successfully applied as targeting agents to enhance drug delivery to prostate cancer [6,7,8] and lymphoblastic leukemia cells [9]

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