Antitumor effects of MsurvivinT34A–CaPi complex-embedded PLGA nanoparticles in combination with Doxil in mice
Source abstract
Abstract
A novel calcium phosphate-pDNA complex-embedded PLGA nanoparticles have been developed for delivering therapy genes. CaPi-Msurvivin T34A-PLGA-NPs (abbreviated as ms-CaPi-PLGA-NPs) containing the MsurvivinT34A plasmid and null-CaPi-PLGA-NPs containing the empty plasmid vector as control were prepared. The nanoparticles had mean size around 130 nm and encapsulation efficiency above 85 %. What is more, the drug loading content and zeta potential of ms-CaPi-PLGA-NPs were 0.734 +/- 0.007 % and -3.75 +/- 1.2 mV, respectively. ms-CaPi-PLGA-NPs combined with Doxil significantly inhibited the proliferation of 4T1 breast cancer cells with IC50 of 0.2937 +/- 0.02 mu g/mL, which was significantly lower than those of Doxil and null-CaPi-PLGA-NPs (p < 0.05). Morphological analysis using Hoechst 33342 and PI staining suggested that a lot of 4T1 cells in combination therapy group of ms-CaPi-PLGA-NPs ? Doxil showed typical morphological characteristic of late apoptosis and necrosis. Flow cytometry analysis with PI and the apoptosis marker Annexin V-FITC staining confirmed that apoptosis fraction given by ms-CaPi-PLGA-NPs ? Doxil was greater than 80 %. Both ms-CaPi-PLGA-NPs and Doxil resulted in cell cycle arrest implying that their synergistic antitumor effect was probably related to the cell cycle regulation. Then, the antitumor effect of ms-CaPi-PLGA-NPs (i.t.) ? Doxil (i.v.) in vivo was studied using BALB/c mice inoculated with 4T1 cells. The result showed that ms-CaPi-PLGA-NPs ? Doxil suppressed the tumor growth most effectively among all the treatment groups. TUNEL assay together with immunohistochemical study on CD31 and VEGF indicated that the ideal antitumor effect of ms-CaPi-PLGA-NPs ? Doxil was ascribed to induction of apoptosis (apoptotic index over 90 %) and inhibition of angiogenesis. Toxicity assessment showed that no significant toxic effects were produced after treatment of ms-CaPi-PLGA-NPs ? Doxil. Above all, we may conclude that the calcium phosphate-pDNA complex-embedded PLGA nanoparticles with good biocompatibility are a promising gene delivery system.
Source: openaire · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Nanoparticle-Based Drug Delivery · RNA Interference and Gene Delivery · Advanced biosensing and bioanalysis techniques
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
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