Abstract
BackgroundMultidrug resistance (MDR) is a pressing obstacle in clinical chemotherapy for breast cancer. Based on the fact that the drug efflux is an important factor in MDR, we designed a codelivery system to guide the drug efflux inhibitor verapamil (VRP) and the chemotherapeutic agent novantrone (NVT) synergistically into breast cancer cells to reverse MDR.ResultsThis co-delivery system consists of following components: the active targeting peptide RGD, an inorganic calcium phosphate (CaP) shell and an organic inner core. VRP and NVT were loaded into CaP shell and phosphatidylserine polyethylene glycol (PS-PEG) core of nanoparticles (NPs) separately to obtain NVT- and VRP-loaded NPs (NV@CaP-RGD). These codelivered NPs allowed VRP to prevent the efflux of NVT from breast cancer cells by competitively combining with drug efflux pumps. Additionally, NV@CaP-RGD was effectively internalized into breast cancer cells by precise delivery through the effects of the active targeting peptides RGD and EPR. The pH-triggered profile of CaP was also able to assist the NPs to successfully escape from lysosomes, leading to a greatly increased effective intracellular drug concentration.ConclusionThe concurrent administration of VRP and NVT by organic/inorganic NPs is a promising therapeutic approach to reverse MDR in breast cancer.
Highlights
Multidrug resistance (MDR) is a pressing obstacle in clinical chemotherapy for breast cancer
We investigated whether NV@CaPRGD can effectively promote the apoptosis of MDR breast cancer cells by inducing mitochondrial apoptosis and inhibiting the extracellular regulated protein kinases (ERK) signaling transduction pathway to achieve the best inhibitory effect on breast cancer cells in vitro [34,35,36,37]
The organic/inorganic codelivery nanoparticles NV@calcium phosphate (CaP)-RGD were prepared by the biomineralization method (Fig. 1a) [38,39,40,41], in which the chemotherapeutic agent NVT was encapsulated into the phosphatidylserine polyethylene glycol (PS-PEG)-RGD micelles and the MDR inhibition agent VRP was adsorbed into the CaP shell
Summary
This co-delivery system consists of following components: the active targeting peptide RGD, an inorganic calcium phosphate (CaP) shell and an organic inner core. VRP and NVT were loaded into CaP shell and phosphatidylserine polyethylene glycol (PS-PEG) core of nanoparticles (NPs) separately to obtain NVT- and VRP-loaded NPs (NV@ CaP-RGD). These codelivered NPs allowed VRP to prevent the efflux of NVT from breast cancer cells by competitively combining with drug efflux pumps. NV@CaP-RGD was effectively internalized into breast cancer cells by precise delivery through the effects of the active targeting peptides RGD and EPR. The pH-triggered profile of CaP was able to assist the NPs to successfully escape from lysosomes, leading to a greatly increased effective intracellular drug concentration
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
