Construction And In Vitro Evaluation Of Tumor Targeting And PH-Responsive Nanoparticle PTEN/PLGA-（HE）₁₀-MAP

Objective To construct a PTEN/PLGA-（HE）₁₀-MAP nanoparticle,which combined with the pH-responsive cell-penetrating peptide（CPP）and encapsulated PTEN plasmid DNA,and to investigate its effects on gene delivery and targeted anti-tumor in vitro.Method The PLGA nanoparticles loading with PTEN were prepared by double emulsification-solvent evaporation method.The nanoparticle PLGA-（HE）₁₀-MAP was prepared by coupling recombinant of pH-responsive oligopeptides and cell-penetrating peptides to the surface through amide condensation reaction.Particle size,Zeta potential,encapsulation rate and drug loading were evaluated to characterize the samples.By analyzing its cytotoxicity,cell uptake,as well as ability to targeted transfection of eukaryotic expression plasmids and anti-tumor cell proliferation,we evaluated its feasibility as a targeted gene delivery system.Results The diameter of PTEN/PLGA-（HE）₁₀-MAP was（266.5±2.86）nm,with the encapsulation efficiency（80.6±6.11）%.The Zeta potential was-（6.7±0.26）m V,+（0.7±0.22）m V and+（37.5±0.85）m V at pH 7.4,7.0and 6.5,respectively.In the cytotoxicity test,the cell survival rates of tumor and normal cells were above 80%.The non-loading PLGA-（HE）₁₀-MAP nanoparticle showed no obvious cytotoxicity.The results of cellular uptake experiments showed that PLGA-（HE）₁₀-MAP was more readily taken up by cells.CCK-8 experimental results showed PTEN/PLGA-（HE）₁₀-MAP could efficiently pH-targeted inhibit proliferation of tumor cell in vitro.Conclusion Nanoparticle PTEN/PLGA-（HE）₁₀-MAP could be a safe and effective gene delivery system and achieve targeted anti-tumor effects in vitro,and may have a certain application prospect in tumor gene therapy.