Mitochondrion targeting peptide-modified magnetic graphene oxide delivering mitoxantrone for impairment of tumor mitochondrial functions

In this study,we prepared mitochondrion targeting peptide-grafted magnetic graphene oxide(GO)nanocarriers for efficient impairment of the tumor mitochondria.The two-dimensional GOMNP-MitP nanosheets were synthesized by grafting magnetic y-Fe_(2)O_(3)to the surface of GO,followed by covalent modification of mitochondrion targeting peptide(MitP).GOMNP-MitP exhibited the high capacity of loading the anticancer drug mitoxantrone(MTX),and preferentially targeted the tumor mitochondria.With the aid of alternating magnetic field(AMF),the MTX-loading GOMNP-MitP released MTX to the mitochondria,severely impairing mitochondrial functions,including attenuation of ATP production,decrease in mitochondrial membrane potential(MMP),and further leading to activation of apoptosis.This study realized high-efficient mitochondrion-ta rgeting drug delivery for anticancer therapy by twodimensional nanoplatforms.

Pathogen infection-responsive nanoplatform targeting macrophage endoplasmic reticulum for treating life-threatening systemic infection

Systemic infections caused by life-threatening pathogens represent one of the main factors leading to clinical death.In this study,we developed a pathogen infection-responsive and macrophage endoplasmic reticulum-targeting nanoplatform to alleviate systemic infections.The nanoplatform is composed of large-pore mesoporous silica nanoparticles(MSNs)grafted by an endoplasmic reticulum-targeting peptide,and a pathogen infection-responsive cap containing the reactive oxygen speciescleavable boronobenzyl acid linker and bovine serum albumin.The capped MSNs exhibited the capacity to high-efficiently load the antimicrobial peptide melittin,and to rapidly release the cargo triggered by H_(2)O_(2) or the pathogen-macrophage interaction system,but had no obvious toxicity to macrophages.During the interaction with pathogenic Candida albicans cells and macrophages,the melittin-loading nanoplatform MSNE+MEL+TPB strongly inhibited pathogen growth,survived macrophages,and suppressed endoplasmic reticulum stress together with pro-inflammatory cytokine secretion.In a systemic infection model,the nanoplatform efficiently prevented kidney dysfunction,alleviated inflammatory symptoms,and protected the mice from death.This study developed a macrophage organelle-targeting nanoplatform for treatment of life-threatening systemic infections.