Synthesis of aptamer decorated dextran coated dendritic mesoporous silica hybrid nanoparticles for colon adenocarcinoma

Mahsa Zahiri,1 Maryam babaei,2 Mohammad ramezani,3 Khalil abnous,4 Seyed mohammad taghdisi,5 Mona alibolandi,6,*

1. 1Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
2. 1Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
3. 1Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
4. 1Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
5. 2Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
6. 1Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Introduction

In spite of the fact that therapeutic approaches including surgery, conventional chemotherapy and radiotherapy have applied for many cancer patients, cancer is still one of the most disastrous diseases which threatens human health. it is evaluated that colorectal cancer is the third deadly malignancy in human. to overcome colon cancer usage of the aforementioned therapeutic approaches has been restricted due to side effects, for example, poor selectivity, cancer resistance, and systemic toxicity. drug delivery systems are efficient systems for local drug delivery at the tumor site without leakage before attaining to the specific organ. silica-based nanoparticles among different nanocarriers which are used in cancer field stand out as the beneficial inorganic carriers for transferring and loading drugs owing to their tolerable surfaces, pore volume, high chemical stability, highly ordered channels. nowadays dendritic mesoporous silica nanoparticles (dmsns) due to their intrinsic physicochemical properties such as their special center-radial mesopore structures, widespread pore size, large mesopore channels and have open 3d dendritic superstructures are developing as an effective nanocarrier for biomedical purposes. in the current study, we report the synthesis and characterization of aptamer-targeted dmsn decorated with dextran for controlled release of doxorubicin (dox). physicochemical properties and the ability of this system for encapsulation and controlled release of doxorubicin was evaluated.

Methods

Dmsns synthesis through sol-gel method. then dextran was electrostatically decorated on the surface of dmsn nanoparticle. after that dox was loaded through the soaking procedure. then targeted and non-targeted systems were evaluated in vitro in terms of their cellular internalization, toxicity, and controlled release efficiency. moreover, dextran decorated dmsn characterized using dls, sem and, tga.

Results

Cellular uptake and mtt assay demonstrated that the developed aptamer-dextran-dmsn-dox had higher cytotoxicity than non-targeted dextran-dmsn-dox in cell cultures. the prepared aptamer-dextran-dmsn-dox system was capable to control the dox release in ph 7.4 while the release of drug was accelerated at ph 5.5.

Conclusion

This work provides a proof-of-concept for the use of this novel nanoparticle-based dmsnps for effective killing of colon cancer cells

Keywords

Dendritic mesoporous silica nanoparticle, dextran, doxorubicin, targeted drug delivery