PH-responsive lipid polymer hybrid nanoparticles (LPHNs) based on poly (β-amino ester) as a promising candidate to resist breast cancers

Abstract

Effective delivery of anti-tumor drugs to the tumor site remain a challenging issue, such as insufficient uptake by tumor cells, degradation by lysosomes and insufficient drug release. Therefore, it is crucial to utilize smart nanoparticles (NPs) designed with the ability to target the tumor site and respond to the unique microenvironment of the tumor tissue. In this paper, we prepared a novel pH responsive core-shell lipid polymer NPs (FA/PBAE/DTX-NPs). The NPs are composed of a mixed lipid shell (DSPE-PEG2000, FA-DSPE-PEG2000 and lecithin) and a polymer core (poly (β-amino ester), PBAE) for targeted delivery of docetaxel (DTX) to breast cancer. FA-PBAE/DTX-NPs had uniform particle size and excellent physical stability. The study of drug release in vitro showed that FA/PBAE/DTX-NPs could release DTX on demand under different pH.Blank NPs were considered nontoxic, while drug-loaded NPs have strong cytotoxicity to 4T1 cells in vitro. The tertiary amine group of PBAE enhanced endosomal/lysosomal escape of the NPs via the proton sponge effect, which triggers the rapid release of DTX. What's more, in vivo experiments have shown that FA/PBAE/DTX-NPs have favorable targeting, antitumor effect, and minimal systemic toxicity in tumor-bearing mice. To sum up, FA/PBAE/DTX-NPs could be selected as a candidate to delivery drug for breast cancer and improving the efficacy of chemotherapy.