Construction and in vitro antitumor effect on prostate cancer of phenylalanine-based poly(ester amide)snanoparticles drug delivery system

Abstract

Objective To study the construction of phenylalanine-based poly(ester amide)sas drug delivery system and its inhibition of in vitro prostate cancer cell LNCaP. Methods The phenylalanine-based poly(ester amide)s nanoparticles were synthesized by nanoprecipitation. The morphology and size distribution of nanoparticle were inspected by transmission electron microscopy and nanoparticle size analyzer. Drug loading and encapsulation rate were measured using fragmentation precipitation method by fluorescent phosphorescence spectrometer. Inhibition of prostate cancer cell LNCaP using doxorubicin-loaded phenylalanine-based poly(ester amide)s nanoparticle were inspected by MTT method and cell apoptosis effect was analyzed by V-APC/7AAD double staining method. Results The phenylalanine-based poly(ester amide)s nanoparticles were synthesized successfully as doxorubicin delivery system with a uniform size of about 90-110 nm. The blank nanoparticles showed a great biocompatibility at different concentrations. The cell viability of LNCaP remained at (95.32±3.97)% at a high blank nanoparticle concentration of 100 μg/ml. Compared with the DOX group whose IC50 was (3.29±0.63) μg/ml, the activity of prostate cancer cells co-cultured with drug-loaded nanoparticles was significantly inhibited, whose IC50 was (1.21±0.43) μg/ml, which was statistically different (t= 6.693, P<0.001). The cell apoptosis effectively induced by drug-loaded nanoparticles was measured by flow cytometry detection. The control group, DOX group and DOX@8p6 group were 2.32%, 29.16% and 61.62%, respectively, while the difference between the three groups was statistically significant (F=294.44, P<0.001), and the DOX@8p6 group had more apoptosis than the DOX group (t=11.238, P<0.001), showing drug-loaded nanoparticles had higher pro-apoptotic efficiency against prostate cancer cell line LNCaP. Conclusion It demonstrated that the biocompatible phenylalanine-based poly(ester amide)s nanoparticles as doxorubicin delivery system could provide effective prostate cancer cell inhibition and high cell apoptosis. Key words: Nanoparticles; Drug delivery; Prostate cancer; Cell inhibition; Cell apoptosis