Changes in target ability of nanoparticles due to protein corona composition and disease state

Many studies have shown the influence of protein corona(PC)on the active targeting capability of ligand-modified nanoparticles;however,the influence of clinical status on PC composition and targeting capacity is rarely discussed.In this study,when transferrinmodified PEGylated polystyrene nanoparticles(Tf-PNs)is intravenously injected into mice with non-small cell lung cancer(NSCLC)comorbid with type 2 diabetes mellitus(T2DM),more Tf-PNs accumulated in the tumor tissue than in those of NSCLC model mice.This indicated that PC derived fromdifferent states of disease changed the active targeting ability of Tf-PNs.To explain the occurrence of this phenomenon,our analysis of PC from different disease states revealed that Tf(transferrin)modification had no significant effect on the formation of PC,and that the PC from the NSCLC comorbid with T2DM model contained more proteins like fibrin and clusterin.This work demonstrates the impacts of comorbidity,such as with T2DM,on the active targeting capability of ligand-modified nanoparticles,and the results promote the application of nanoparticles for precision medicine.

The reversal effect of capsaicin on doxorubicin-resistant breast cancer cells

Overexpression of P-glycoprotein(P-gp),encoded by the MDR1 gene,in tumor cells curtails the efficacy of chemotherapy,leading to multidrug resistance(MDR),which can be reversed by the P-gp inhibitor.Capsaicin,the principal pungent component of hot chili,is a reported P-gp inhibitor with anti-cancer properties.In the present study,we aimed to evaluate the MDR reversal effect of capsaicin.The MCF-7/DOX cells were treated with capsaicin for a short term(3 h)or long term(72 h).The cytotoxicity studies were completed by using the SRB method.RT-PCR method was utilized to evaluate the effect of capsaicin on the expression of MDR1 at the m RNA level.The accumulation and subcellular distribution studies were implemented to further investigate the reversal effect of capsaicin.The effect of capsaicin on the ATP production of mitochondria was also evaluated.The results of the cytotoxicity study indicated that capsaicin(50μM)reversed the resistance of MCF-7/DOX cells to doxorubicin(DOX)with the reversal fold of 4.68,and concentration-dependently down-regulated the expression of MDR1 at the m RNA level after long-term(72 h)incubation.After short-term(3 h)incubation,capsaicin reversibly and concentration-dependently increased the accumulation of DOX into MCF-7/DOX cells and induced a different subcellular distribution of DOX compared with verapamil as a positive control.The ATP production of mitochondria was also concentration-dependently inhibited by capsaicin.In conclusion,capsaicin was capable of reversing the resistance of MCF-7/DOX cells to DOX,making it a promising lead compound for MDR reversal.