Chitosan-Based Polymeric Nanoparticles as an Efficient Gene Delivery System to Cross Blood Brain Barrier: In Vitro and In Vivo Evaluations

Author:

Khan Ishaq N.12,Navaid Shiza3,Waqar Walifa4,Hussein Deema5ORCID,Ullah Najeeb2ORCID,Khan Muhammad Umar Aslam67ORCID,Hussain Zakir3ORCID,Javed Aneela4

Affiliation:

1. MIT Media Lab, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

2. Cancer Cell Culture & Precision Oncomedicine Lab, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar 25100, Pakistan

3. School of Chemical and Materials Engineering, National University of Sciences and Technology, Islamabad 44000, Pakistan

4. Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad 44000, Pakistan

5. Neurooncology Translational Group, King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia

6. Department of Mechanical and Industrial Engineering, Qatar University, Doha 2713, Qatar

7. Biomedical Research Center, Qatar University, Doha 2713, Qatar

Abstract

Significant progress has been made in the field of gene therapy, but effective treatments for brain tumors remain challenging due to their complex nature. Current treatment options have limitations, especially due to their inability to cross the blood-brain barrier (BBB) and precisely target cancer cells. Therefore options that are safer, more effective, and capable of specifically targeting cancer cells are urgently required as alternatives. This current study aimed to develop highly biocompatible natural biopolymeric chitosan nanoparticles (CNPs) as potential gene delivery vehicles that can cross the BBB and serve as gene or drug delivery vehicles for brain disease therapeutics. The efficiency of the CNPs was evaluated via in vitro transfection of Green Fluorescent Protein (GFP)-tagged plasmid in HEK293-293 and brain cancer MG-U87 cell lines, as well as within in vivo mouse models. The CNPs were prepared via a complex coacervation method, resulting in nanoparticles of approximately 260 nm in size. In vitro cytotoxicity analysis revealed that the CNPs had better cell viability (85%) in U87 cells compared to the chemical transfection reagent (CTR) (72%). Moreover, the transfection efficiency of the CNPs was also higher, as indicated by fluorescent emission microscopy (20.56% vs. 17.79%) and fluorescent-activated cell sorting (53% vs. 27%). In vivo assays using Balb/c mice revealed that the CNPs could efficiently cross the BBB, suggesting their potential as efficient gene delivery vehicles for targeted therapies against brain cancers as well as other brain diseases for which the efficient targeting of a therapeutic load to the brain cells has proven to be a real challenge.

Funder

National University of Sciences and Technology (NUST)’s Student Research Fund

Higher Education Commission (HEC) of Pakistan

Publisher

MDPI AG

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