NVP-BEZ235/Chlorin-e6 co-loaded nanoparticles ablate breast cancer by biochemical and photodynamic synergistic effects

Seeking profitable therapies for triple-negative breast cancer （TNBC） has attracted intense research interest. However, an efficient cure for TNBC remains an unresolved challenge in oncology. Herein, for the first time, we describe the use of polymeric nanoparticles loaded with NVP-BEZ235 and Chlorin-e6, denoted as NVP/Ce6@NPs, to overcome the adaptive treatment tolerance of TNBC by taking advantage of the synergistic effect .between biochemical and photodynamic therapies. Upon laser irradiation, the NVP/Ce6@NPs generated reactive oxygen species （ROS） and efficiently induced the apoptosis of tumor cells through DNA damage. Furthermore, the released NVP-BEZ235 could prevent Chkl phosphorylation-induced DNA damage repair, thus enhancing the sensitivity of tumor cells to ROS. Animal studies on mice bearing an MDA-MB-231 tumor validated that the NVP/Ce6@NPs had a greater therapeutic efficacy compared to that of monotherapies, with an inhibition ratio of 89.3%. Western blotting and cell viability analyses confirmed the inhibition of both MDA-MB-231 cell proliferation and Chkl phosphorylation by NVP/Ce6@NPs. These findings provide a rational understanding of the synergistic effect of the biochemical/photodynamic therapy and pave the way for the development of efficient therapeutic approaches to fight against TNBC.

The protein corona modulates the inflammation inhibition by cationic nanoparticles via cell-free DNA scavenging

A central paradigm in nanomedicine is that when synthetic nanoparticles(NPs)enter the body,they are immediately cloaked by a corona of macromolecules(mostly proteins)that mediates the role of the physico-chemical properties in the NP biological functions(the“coronation paradigm”).In this work,we focused on the assessment of the“coronation paradigm”for cationic NPs(cNPs)used as rheumatoid arthritis(RA)drugs due to their ability to scavenge cell-free DNA(cfDNA).We fabricated series of cNPs uniformly coated with single or di-hydroxyl groups and different types of amino groups and showed that hydroxylated nanoparticles displayed a prolonged retention in inflamed joints and greater anti-inflammatory effect in collagen-induced arthritis(CIA)rats than the non-hydroxylated analogues.Especially,the cNPs with secondary amines and a di-hydroxyl shell showed the best performance among the tested cNPs.Proteomic analysis showed that the cNPs with a di-hydroxyl shell adsorbed less opsonin proteins than the cNPs carrying mono hydroxyl groups and non-hydroxylated ones,which may provide a mechanistic explanation for the different biodistribution profiles of cNPs.Thus,this study suggests that the protein corona mediates the effects of the surface chemistry on the fate and functions of cNPs as anti-RA drugs.