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A Unique Core-Shell Structured, Glycol Chitosan-Based Nanoparticle Achieves Cancer-Selective Gene Delivery with
Bei Cheng1, Hye-Hyun Ahn1, Hwanhee Nam1,2
1Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Abstract:
The inherent instability of nucleic acids within serum and the tumor microenvironment necessitates a suitable vehicle for non-viral gene delivery to malignant lesions. A specificity-conferring mechanism is also often needed to mitigate off-target toxicity. In the present study, we report a stable and efficient redox-sensitive nanoparticle system with a unique core-shell structure as a DNA carrier for cancer theranostics. Thiolated polyethylenimine (PEI-SH) is complexed with DNA through electrostatic interactions to form the core, and glycol chitosan-modified with succinimidyl 3-(2-pyridyldithio)propionate (GCS-PDP) is grafted on the surface through a thiolate-disulfide interchange reaction to form the shell. The resulting nanoparticles, GCS-PDP/PEI-SH/DNA nanoparticles (GNPs), exhibit high colloid stability in a simulated physiological environment and redox-responsive DNA release. GNPs not only show a high and redox-responsive cellular uptake, high transfection efficiency, and low cytotoxicity in vitro, but also exhibit selective tumor targeting, with minimal toxicity, in vivo, upon systemic administration. Such a performance positions GNPs as viable candidates for molecular-genetic imaging and theranostic applications.
Insights
Researchers developed stable, redox-sensitive nanoparticles for targeted cancer gene therapy. These nanoparticles effectively deliver DNA to tumors, showing high efficiency and low toxicity for improved cancer theranostics.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cancer Research
Background:
- Nucleic acid instability in serum and tumor microenvironments hinders non-viral gene delivery.
- Off-target toxicity is a significant challenge in cancer gene therapy, requiring targeted delivery systems.
Purpose of the Study:
- To develop a stable and efficient redox-sensitive nanoparticle system for cancer theranostics.
- To create a core-shell nanoparticle capable of targeted DNA delivery and controlled release.
Main Methods:
- Fabrication of core-shell nanoparticles using thiolated polyethylenimine (PEI-SH) complexed with DNA (core) and glycol chitosan-modified with succinimidyl 3-(2-pyridyldithio)propionate (GCS-PDP) (shell).
- Evaluation of nanoparticle colloid stability, redox-responsive DNA release, cellular uptake, transfection efficiency, and cytotoxicity in vitro.
- Assessment of in vivo tumor targeting, biodistribution, and toxicity following systemic administration.
Main Results:
- The resulting GCS-PDP/PEI-SH/DNA nanoparticles (GNPs) demonstrated high colloid stability in physiological environments.
- GNPs exhibited redox-responsive DNA release, high cellular uptake, efficient transfection, and low cytotoxicity in vitro.
- In vivo studies showed selective tumor targeting and minimal toxicity of GNPs upon systemic administration.
Conclusions:
- The developed GNPs represent a stable and efficient non-viral gene delivery vehicle for cancer theranostics.
- The redox-sensitive nature and targeted delivery capabilities position GNPs for molecular-genetic imaging and therapeutic applications.
