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Cationic nanoparticles with quaternary ammonium-functionalized PLGA–PEG-based copolymers for potent gene transfection

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Abstract

The objective of the present work was to develop new cationic nanoparticles (cNPs) with amphiphilic cationic copolymers for the delivery of plasmid DNA (pDNA). Cationic copolymers were built on the synthesis of quaternary ammonium salt compounds from diethylenetriamine (DETA) to include the positively charged head group and amphiphilic multi-grafts. PLGA-phe-PEG-qDETA (PPD), phe-PEG-qDETA-PLGA (PDP), and PLGA-phe-PEG-qDETA-PLGA (PPDP) cationic copolymers were created by this moiety of DETA quaternary ammonium, heterobifunctional polyethylene glycol (COOH-PEG-NH2), phenylalanine (phe), and poly(lactic-co-glycolic acid) (PLGA). These new cNPs were prepared by the water miscible solvent displacement method. They exhibit good pDNA binding ability, as shown in a retardation assay that occurred at a particle size of ~217 nm. The zeta potential was approximately +21 mV when the cNP concentration was 25 mg/ml. The new cNPs also have a better buffering capacity than PLGA NPs. However, the pDNA binding ability was demonstrated starting at a weight ratio of approximately 6.25 cNPs/pDNA. Gene transfection results showed that these cNPs had transfection effects similar to those of Lipofectamine 2000 in 293T cells. Furthermore, cNPs can also transfect human adipose-derived stem cells. The results indicate that the newly developed cNP is a promising candidate for a novel gene delivery vehicle.

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Acknowledgments

The authors gratefully acknowledge the support for this research by the Ministry of Economic Affairs, and National Science Council in Taiwan under the Grant Numbers 100-EC-17-A-19-S1-176, NSC 99-2628-E-037-003, and the Kaohsiung Medical University Hospital (KMUH99-9R36, KMUH100-0R40), respectively.

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Authors and Affiliations

  1. School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Yan-Hsung Wang

  2. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Yin-Chih Fu

  3. Department of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung, 807, Taiwan

    Hui-Chi Chiu, Shao-Ping Lo & Chih-Kuang Wang

  4. Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Chau-Zen Wang & Mei-Ling Ho

  5. Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Po-Len Liu

  6. Department of Orthopaedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Yin-Chih Fu

  7. Department of Orthopaedics, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Yin-Chih Fu

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  1. Yan-Hsung Wang
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Correspondence to Chih-Kuang Wang.

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Yan-Hsung Wang and Yin-Chih Fu contributed equally to this study.

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Wang, YH., Fu, YC., Chiu, HC. et al. Cationic nanoparticles with quaternary ammonium-functionalized PLGA–PEG-based copolymers for potent gene transfection. J Nanopart Res 15, 2077 (2013). https://doi.org/10.1007/s11051-013-2077-4

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