A Unique Core–Shell Structured, Glycol Chitosan-Based Nanoparticle Achieves Cancer-Selective Gene Delivery with Reduced Off-Target Effects
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 an...
| Main Authors: | , , , , , , |
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| Format: | Article |
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MDPI AG
2022-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/2/373 |
| _version_ | 1797477175653302272 |
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| author | Bei Cheng Hye-Hyun Ahn Hwanhee Nam Zirui Jiang Feng J. Gao Il Minn Martin G. Pomper |
| author_facet | Bei Cheng Hye-Hyun Ahn Hwanhee Nam Zirui Jiang Feng J. Gao Il Minn Martin G. Pomper |
| author_sort | Bei Cheng |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T21:13:55Z |
| format | Article |
| id | doaj.art-5b3f1e186ead44b4bce17988f03ed13d |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T21:13:55Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-5b3f1e186ead44b4bce17988f03ed13d2023-11-23T21:38:16ZengMDPI AGPharmaceutics1999-49232022-02-0114237310.3390/pharmaceutics14020373A Unique Core–Shell Structured, Glycol Chitosan-Based Nanoparticle Achieves Cancer-Selective Gene Delivery with Reduced Off-Target EffectsBei Cheng0Hye-Hyun Ahn1Hwanhee Nam2Zirui Jiang3Feng J. Gao4Il Minn5Martin G. Pomper6Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USAThe 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.https://www.mdpi.com/1999-4923/14/2/373molecular-genetic imagingreporter–probe pairgene deliverysystemic deliverytoxicity |
| spellingShingle | Bei Cheng Hye-Hyun Ahn Hwanhee Nam Zirui Jiang Feng J. Gao Il Minn Martin G. Pomper A Unique Core–Shell Structured, Glycol Chitosan-Based Nanoparticle Achieves Cancer-Selective Gene Delivery with Reduced Off-Target Effects Pharmaceutics molecular-genetic imaging reporter–probe pair gene delivery systemic delivery toxicity |
| title | A Unique Core–Shell Structured, Glycol Chitosan-Based Nanoparticle Achieves Cancer-Selective Gene Delivery with Reduced Off-Target Effects |
| title_full | A Unique Core–Shell Structured, Glycol Chitosan-Based Nanoparticle Achieves Cancer-Selective Gene Delivery with Reduced Off-Target Effects |
| title_fullStr | A Unique Core–Shell Structured, Glycol Chitosan-Based Nanoparticle Achieves Cancer-Selective Gene Delivery with Reduced Off-Target Effects |
| title_full_unstemmed | A Unique Core–Shell Structured, Glycol Chitosan-Based Nanoparticle Achieves Cancer-Selective Gene Delivery with Reduced Off-Target Effects |
| title_short | A Unique Core–Shell Structured, Glycol Chitosan-Based Nanoparticle Achieves Cancer-Selective Gene Delivery with Reduced Off-Target Effects |
| title_sort | unique core shell structured glycol chitosan based nanoparticle achieves cancer selective gene delivery with reduced off target effects |
| topic | molecular-genetic imaging reporter–probe pair gene delivery systemic delivery toxicity |
| url | https://www.mdpi.com/1999-4923/14/2/373 |
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