Xinyuan Zhu

Construction and application of pH-triggered cleavable hyperbranched polyacylhydrazone for drug delivery

Polymeric drug carriers with high stability during long circulation and triggered degradation after drug release are particularly interesting in drug delivery. Here, a novel pH-triggered backbone-cleavable hyperbranched polyacylhydrazone (HPAH) was successfully prepared through a simple polycondensation of 2,3-butanedione and 1-(2-aminoethyl) piperazine tri-propionylhydrazine. The experimental results showed that the degree of branching (DB) of HPAH was 0.60, and the weight-average molecular weight (Mw) of end-capped HPAH was 4.0 × 103 with a polydipersity index (PDI) of 1.6. 2D DOSY NMR degradation experiments demonstrated that HPAH was stable in neutral conditions while cleavable in acidic environments. Owing to the existence of numerous acylhydrazine terminals, the anticancer drug doxorubicin (DOX) was conjugated to hydrophilic HPAH. The obtained HPAH-DOX conjugate could self-assemble into polymeric micelles with an average diameter of 20 nm, which were stable under physiological pH but cleavable after endocytosis. Cell viability of HPAH, monomers, and degradation products was maintained above 70% over the culture periods, even when the concentration was up to 3 mg mL−1 according to methyl tetrazolium (MTT) assay in NIH/3T3 cell line. Both flow cytometry and confocal laser scanning microscopy (CLSM) confirmed the high cellular uptake of HPAH-DOX. Anti-cancer effect was evaluated in HeLa cell line, and the DOX dose required for 50% cellular growth inhibition was found to be 3.5 μg mL−1 by MTT assay.

Photodynamic therapy with hyperbranched poly(ether-ester) chlorin(e6) nanoparticles on human tongue carcinoma CAL-27 cells

BACKGROUNDnHyperbranched polymers represent a new class of drug-delivery vehicle that can be used to prepare nanoparticles with uniform size distribution.nnnMETHODSnIn this study we prepared covalent conjugates between the photosensitizer chlorin(e6) and hyperbranched poly(ether-ester), HPEE. HPEE-ce6 nanoparticles were synthesized by carbodiimide-mediated reaction between HPEE and ce6, and characterized by ultraviolet-visible absorption spectroscopy (UV-Vis), and transmission electron microscopy (TEM). The uptake and phototoxicity of HPEE-ce6 nanoparticles towards human oral tongue cancer CAL-27 cells was detected by confocal laser scanning microscopy (CLSM) and MTT assay, respectively.nnnRESULTSnThe absorption peak of HPEE-ce6 nanoparticles was red-shifted 12-nm compared with ce6, and TEM showed uniform nanoparticles with a diameter of 50-nm. HPEE-ce6 nanoparticles were taken up by CAL-27 cells after 4h incubation and localized in the cytoplasm. The MTT assay showed a significantly (P<0.05) higher phototoxicity compared to free ce6 after 12 J/cm² of 660-nm laser illumination.nnnCONCLUSIONSnThis is the first time to our knowledge that hyperbranched polymers have been used in PDT drug delivery.

Self-assembly of CdTe nanocrystals at the water/oil interface by amphiphilic hyperbranched polymers.

A general strategy for realizing the self-assembly of aqueous CdTe nanocrystals (NCs) at the water/oil interface by means of an amphiphilic core-shell hyperbranched polymer has been proposed. Aqueous CdTe NCs were firstly transferred into the chloroform phase in the presence of palmityl chloride functionalized hyperbranched poly(amidoamine) (HPAMAM-PC), and then self-assembled at the water/chloroform interface by decreasing the pH value of the aqueous phase or introducing α-CDs to the aqueous phase. The resulting CdTe/HPAMAM-PC self-assembly film was characterized by fluorescence microscopy, UV-vis, PL, TEM, EDS, FT-IR, DSC and TGA.

Cationic long-chain hyperbranched poly(ethylene glycol)s with low charge density for gene delivery

A series of cationic long-chain hyperbranched poly(ethylene glycol)s (HPEGs) with low charge density were designed and synthesized. Through one-pot Michael-addition reaction of poly(ethylene glycol) diacrylate and 2,2′-(ethylenedioxy)bis(ethylamine), cationic long-chain HPEGs with different degrees of branching were obtained, which was confirmed by 1D and 2D NMR, FTIR, DSC and SEC-MALLS. Different from the traditional surface PEGylation strategy, the backbone of HPEGs consisted of oligo-ethylene glycol and biodegradable ester connections. Therefore, HPEGs showed low cytotoxicity. Due to the existence of low charge density in the polymeric backbone, the cationic HPEGs could form negatively charged loose polyplexes with plasmid DNA (pDNA), which was confirmed by zeta-potential measurements, agarose gel electrophoresis, circular dichroism and atomic force microscopy. The fluorescence microscopic studies demonstrated that the HPEG–pDNA polyplexes with low negative charges could be efficiently internalized by cells through endocytosis, exhibiting high transfection efficiency. By combining the advantages of a long-chain hyperbranched structure and PEG, cationic HPEGs provide a new opportunity for developing safe and efficient gene vectors.