Tumor-targeting, pH-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells

International Journal of Nanomedicine
Tuan Hiep TranJong Oh Kim

Abstract

The attachment of polyethylene glycol (PEG) increases the circulation time of drug-containing nanoparticles; however, this also negatively affects cellular uptake. To overcome this problem, unique lipid polymer hybrid (LPH) nanoparticles were developed with a pH-responsive PEG layer that detached prior to cell uptake. Docetaxel (DTX) was incorporated into the lipid core of the nanoparticles, which was then shielded with the pH-responsive block co-polymer polyethylene glycol-b-polyaspartic acid (PEG-b-PAsp) using a modified emulsion method. The optimized LPH nanoparticles were ~200 nm and had a narrow size distribution. Drug release from DTX-loaded LPH (DTX-LPH) nanoparticles was pH-sensitive, which is beneficial for tumor targeting. More importantly, DTX-LPH nanoparticles were able to effectively induce apoptosis in cancer cells. The negative surface charge and PEG shell of vehicle remarkably enhanced the blood circulation and physiological activity of DTX-LPH nanoparticles compared with that of free DTX. The nanoparticles were also found to reduce the size of tumors in tumor-bearing xenograft mice. The in vivo anticancer effect of DTX-LPH nanoparticles was further confirmed by the elevated levels of caspase-3 and poly ADP ribo...Continue Reading

Citations

Jan 28, 2021·Drug Delivery·Jingou LiangLei Cheng
Nov 23, 2021·Pharmaceutical Development and Technology·Roshan KatekarJiaur R Gayen

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Methods Mentioned

BETA
xenograft
dynamic light scattering
transmission electron microscopy
atomic force microscopy
X-ray
flow
flow cytometry
Protein Assay
xenografts
confocal microscopy

Software Mentioned

Win
NanoDTS
NonLin

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