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YONG Qin, YUE Hanxun, SHI Min, HUANG Shiqin, ZHAO Xuan, YU Xian. Construction and in vitro evaluation of pH-responsive and tumor-targeted PTEN/PLGA-(HE)10-MAP nanoparticles[J]. Journal of China Pharmaceutical University, 2021, 52(3): 301-310. DOI: 10.11665/j.issn.1000-5048.20210306
Citation: YONG Qin, YUE Hanxun, SHI Min, HUANG Shiqin, ZHAO Xuan, YU Xian. Construction and in vitro evaluation of pH-responsive and tumor-targeted PTEN/PLGA-(HE)10-MAP nanoparticles[J]. Journal of China Pharmaceutical University, 2021, 52(3): 301-310. DOI: 10.11665/j.issn.1000-5048.20210306
shu

Construction and in vitro evaluation of pH-responsive and tumor-targeted PTEN/PLGA-(HE)10-MAP nanoparticles

  • 1.

    Phase I Clinical Trial Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010

  • 2.

    Department of Pharmacy, Central Hospital of Luohe, Luohe 462000

  • 3.

    Department of Pharmacy, Central Hospital of Jiangjin District, Chongqing 402260, China

Funds: This study was supported by the National Natural Science Foundation of China (No. 82072327)
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  • Received Date: November 29, 2020
  • Revised Date: May 25, 2021
    Graphical Abstract
    • Abstract
  • To construct PTEN/PLGA-(HE)10-MAP nanoparticles, which encapsulated PTEN plasmid DNA and combined with the pH-responsive cell-penetrating peptides (CPPs), and to investigate their effects of gene delivery and anti-tumor targets in vitro. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with PTEN plasmid DNA were prepared by double emulsification-solvent evaporation method. PTEN/PLGA-(HE)10-MAP nanoparticles were prepared by coupling the histidine-glutamic acid-model amphipathic peptide nanocomplex [(HE)10-MAP] to the surface through amide condensation reaction. Particle size, Zeta potential, encapsulation rate and drug loading were tested to characterize the nanoparticles. By analyzing the cytotoxicity, cellular uptake, targeted transfection of eukaryotic expression plasmids and anti-tumor cell proliferation, the feasibility as a targeted gene delivery system were evaluated. The particle size of PTEN/PLGA-(HE)10-MAP nanoparticles was (266.5 ± 2.86) nm, with the encapsulation efficiency (80.6 ± 6.11)%. Zeta potentials were -(6.7 ± 0.26) mV, +(0.7 ± 0.22) mV and +(37.5 ± 0.85) mV at pH 7.4, 7.0 and 6.5, respectively. In the cytotoxicity test, the cell survival rates of tumor and normal cells were above 80%.Non-loading PLGA-(HE)10-MAP nanoparticles showed no obvious cytotoxicity. The results of cellular uptake experiments showed that PTEN/PLGA-(HE)10-MAP nanoparticles were more readily taken up by cells.The results of CCK-8 showed that the nanoparticles could pH-specifically inhibit proliferation of tumor cell in vitro.And PTEN/PLGA-(HE)10-MAP nanoparticles may be applied in tumor gene therapy.
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    • References (26)
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