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Developing safe and effective nonviral gene vector ishighly crucialfor successful gene therapy. In the present study, we designed a seriesof biodegradable micelles based on hybrid polypeptide copolymers ofpoly(ethylene glycol)-b-poly(l-lysine)-b-poly(l-leucine) (PEG-PLL-PLLeu) for efficientgene delivery. A group of amphiphilic PEG-PLL-PLLeu hybrid polypeptidecopolymers were synthesized by ring-opening polymerization of N-carboxyanhydride, and the chemical structure of each copolymerwas characterized by 1H NMR and FT-IR spectroscopy measurement.The PEG-PLL-PLLeu micelles were positively charged with tunable sizesranging from 40 to 90 nm depending on the length of PLL and PLLeusegment. Compared with PEG-PLL copolymers, PEG-PLL-PLLeu micellesdemonstrated significantly higher transfection efficiency and lesscytotoxicity. Furthermore, the transfection efficiency and biocompatibilityof the micelles can be simultaneously improved by tuning the lengthof PLL and PLLeu segments. The transfection efficiency of PEG-PLL-PLLeumicelles in vivo was two to three times higher than that of PEI25k, which was attributable to their capability of promotingDNA condensation and cell internalization as well as successful lysosomeescape. Hence well-defined PEG-PLL-PLLeu micelles would serve as highlyeffective nonviral vectors for in vivo gene delivery. [ABSTRACT FROM AUTHOR]

Smac-conjugated nanoparticle (Smac-NP) was designed to induce the apoptosis of cancer cells and as a drug carrier for combination therapy. It contained three parts, a SmacN7 peptide which could induce apoptosis of cancer cells by interacting with XIAPs, the cell penetrating domain rich in arginine, and four hydrophobic tails for self-assembled Smac-NP. We demonstrated that Smac-NPs exerted an antitumor effect in breast cancer cell MDA-MB-231 and nonsmall lung cancer (NSCLC) cell H460, which efficiently inhibited cancer cells proliferation without influencing normal liver cell lines LO2. Smac-NPs also significantly induced apoptosis of MDA-MB-231 and H460 cells through activating pro-caspase-3, down-regulating the expression of antiapoptotic protein Bcl-2 and up-regulating the pro-apoptotic protein Bax. Furthermore, Smac-NPs could be explored as a drug delivery system to load hydrophobic drug such as DOX for combination therapy. The DOX-loaded nanoparticles (DOX-Smac-NPs) exhibited higher cellular uptake efficiency and antitumor effect. Our work provided a new insight into therapeutic peptides integrated with drug simultaneously in one system for cancer combination treatment.

Indocyanine green (ICG) is a near-infrared (NIR) fluorescence dye for extensive applications; however, it is limited for further biological application due to its poor aqueous stability in vitro, concentration-dependent aggregation, rapid elimination from the body, and lack of target specificity. To overcome its limitations, ICG was encapsulated in the core of a polymeric micelle, which self-assembled from amphiphilic PEG-polypeptide hybrid triblock copolymers of poly(ethylene glycol)-b-poly(l-lysine)-b-poly(l-leucine) (PEG-PLL-PLLeu), with PLLeu as the hydrophobic core and PEG as the hydrophilic shell. The ICG was associated with the hydrophobic core via hydrophobic interaction and also the hydrophilic heads through electrostatic attractive interaction. Compared with free ICG, PEG-PLL-PLLeu-ICG micelles significantly improved quantum yield and fluorescent stability. The cellular uptake experiments showed that PEG-PLL-PLLeu-ICG micelles have a high cellular uptake rate. And the in vivo experiments revealed the excellent passive tumor targeting ability and long circulation time of PEG-PLL-PLLeu-ICG. The above results indicated the broad prospects of PEG-PLL-PLLeu-ICG application in the fields of tumor diagnosis and imaging. In addition, temperature measurements under NIR laser irradiation and in vitro photothermal ablation studies proved the potential application of PEG-PLL-PLLeu-ICG in tumor photothermal therapy.

We synthesized a new class of mutifunctional multidentate-imidazole polymer ligands by one-step reaction to produce conjugation-ready QDs with great stability and compact size. Furthermore, combined with strain-promoted click chemistry, we developed a general strategy for efficient labeling of living-viruses with QD probes.