The mitochondria-targeted TPP-PEI-LND was synthesized by mitochondria-targeted ligand triphenylphosphine(TPP)and therapeutic drug lonidamine(LND)conjugated to low molecular weight branched polyethyleneimine(PEI). TPP-PEI-LND was verified using 1H NMR; in vitro release was determined by the dialysis. Besides, the cytotoxicity and mitochondria-targeted potential of TPP-PEI-LND were investigated in HeLa cells. The results showed that TPP-PEI-LND was successfully synthesized and it exhibited the feature of extended-release. Hence, TPP-PEI-LND could deliver LND to mitochondria, resulting in significantly enhanced efficacy of LND.

Liver fibrosis is a major disease that affects human health. Currently,drugs used for the treatment of hepatic fibrosis have such problems as low drug solubility,lack of liver specificity and possible occurrence of side-effects. In order to improve the anti-fibrosis therapeutic efficacy,various nano-drug delivery systems and targeting strategies are explored in liver fibrosis therapy. This review summarizes the drug delivery systems and targeting strategies that have been applied to liver fibrosis therapy in recent years from the types of carriers and modified ligands,which serve as a basis of designing safe and effective drug delivery systems for liver fibrosis therapy.

Biodegradable polyamines have long been studied as potential recombinant viral gene vectors. Spermine (SPE) is an endogenous tetra-amine with excellent biocompatibility yet poor gene condensation capacity. We have previously synthesized a polyspermine based on SPE and poly(ethylene glycol) (PEG) diacrylate (SPE-alt-PEG) for enhanced transfection performance, but the synthesized SPE-alt-PEG still lacked specificity towards cancer cells. In this study, folic acid (FA) was incorporated into SPE-alt-PEG to fabricate a targeted gene delivery vector (FA-SPE-PEG) via an acylation reaction. FA-SPE-PEG exhibited mild cytotoxicity in both cancer cells and normal cells. FA-SPE-PEG possessed higher transfection efficiency than PEI 25 K and Lipofectamine(®) 2000 in two tested cancer cell lines at functional weight ratios, and its superiority over untargeted SPE-alt-PEG was prominent in cells with overexpressed folate receptors (FRs). Moreover, in vivo delivery of green fluorescent protein (GFP) with FA-SPE-PEG resulted in highest fluorescent signal intensity of all investigated groups. FA-SPE-PEG showed remarkably enhanced specificity towards cancer cells both in vivo and in vitro due to the interaction between FA and FRs. Taken together, FA-SPE-PEG was demonstrated to be a prospective targeted gene delivery vector with high transfection capacity and excellent biocompatibility.