Search

A new type of biodegradable micelles for glutathione-mediated intracellular drug delivery was developed on the basis of an amphiphilic hyperbranched multiarm copolymer (H40-star-PLA-SS-PEP) with disulfide linkages between the hydrophobic polyester core and hydrophilic polyphosphate arms. The resulting copolymers were characterized by nuclear magnetic resonance (NMR), Fourier transformed infrared (FTIR), gel permeation chromatography (GPC), and differential scanning calorimeter (DSC) techniques. Benefiting from amphiphilic structure, H40-star-PLA-SS-PEP was able to self-assemble into micelles in aqueous solution with an average diameter of 70 nm. Moreover, the hydrophilic polyphosphate shell of these micelles could be detached under reduction-stimulus by in vitro evaluation, which resulted in a rapid drug release due to the destruction of micelle structure. The glutathione-mediated intracellular drug delivery was investigated against a Hela human cervical carcinoma cell line. Flow cytometry and confocal laser scanning microscopy (CLSM) measurements demonstrated that H40-star-PLA-SS-PEP micelles exhibited a faster drug release in glutathione monoester (GSH-OEt) pretreated Hela cells than that in the nonpretreated cells. Cytotoxicity assay of the doxorubicin-loaded (DOX-loaded) micelles indicated the higher cellular proliferation inhibition against 10 mM of GSH-OEt pretreated Hela cells than that of the nonpretreated ones. As expected, the DOX-loaded micelles showed lower inhibition against 0.1 mM of buthionine sulfoximine (BSO) pretreated Hela cells. These reduction-responsive and biodegradable micelles show a potential to improve the antitumor efficacy of hydrophobic chemotherapeutic drugs.

A novel narrowly-distributed (ND) polymeric micelle obtained in combination with host-guest recognition and self-assembly is reported. First, the adamantyl-terminated hyperbranched poly[3-ethyl-3-(hydroxymethyl)oxetane] (HBPO-AD) was synthesized by esterification of hyperbranched poly[3-ethyl-3-(hydroxymethyl)oxetane] (HBPO) with 1-adamantanecarbonyl chloride. Then the ND polymeric core-shell micelles, with the hydrophobic HBPO-AD cores and hydrophilic beta-cyclodextrin (β-CD) shells, were prepared via host-guest inclusion complexation of HBPO-AD and β-CD. The resultant polymer micelles were well characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Interestingly, after annealing at a temperature above the glass transition temperature (T(g)) for a certain time, the polymeric micelles can further self-assemble and fuse into two-dimensional (2D) sheets. The TEM, SEM and atomic force microscopy (AFM) characterization validate that the sheets are formed through stacking and fusion of tightly packed nanoparticles. In addition, the formation mechanism of polymeric complex micelles and 2D sheets has also been discussed.

A novel type of amphiphilic hyperbranched multiarm copolymer [H40-star-(PLA-b-PEP-OH)] was synthesized through a two-step ring-opening polymerization (ROP) procedure and applied to drug delivery. First, Boltorn H40 was used as macroinitiator for the ROP of L-lactide to form the intermediate (H40-star-PLA-OH). Then, the ROP of ethyl ethylene phosphate was further initiated to produce H40-star-(PLA-b-PEP-OH). The resulting hyperbranched multiarm copolymers were characterized by (1)H, (13)C, and (31)P NMR, GPC, and FTIR spectra. Benefiting from the amphiphilic structure, H40-star-(PLA-b-PEP-OH) was able to self-assemble into micelles in water with an average diameter of 130 nm. In vitro evaluation of these micelles demonstrated their excellent biocompatibility and efficient cellular uptake by methyl tetrazolium assay, flow cytometry, and confocal laser scanning microscopy measurements. Doxorubicin-loaded micelles were investigated for the proliferation inhibition of a Hela human cervical carcinoma cell line, and the Doxorubicin dose required for 50% cellular growth inhibition was found to be 1 microg/mL. These results indicate that H40-star-(PLA-b-PEP-OH) micelles can be used as safe, promising drug-delivery systems.

A Zinc phthalocyanine-based (ZnPc–PA) polymeric micelle around 70 nm and with dual-modal PTT/PDT functions for non-antibiotic bacteria eradication was developed. It showed an excellent bacterial killing efficiency of 95.2% and 96.7% in vitro against Methicillin-resistant Staphylococcus aureus (MRSA) and its biofilm, respectively. Furthermore, the in vivo experiments proved its great potential for implant-associated infection (IAI). [ABSTRACT FROM AUTHOR]

As a kind of promising drug carriers, smart polymers have attracted much attention due to the effective and controlled drug release in target cells. Herein, a reactive oxygen species (ROS)‐responsive thioether‐containing amphiphilic hyperbranched polymer prepared from MTPA and TMPTGE (HBPMT) is synthesized from 3‐(methylthio)propylamine (MTPA) and trimethylolpropane triglycidyl ether (TMPTGE) by the amine‐epoxy click reaction via A2 + B3 one‐pot approach. Benefiting from its inherent amphiphilic nature, HBPMT can self‐assemble into stable micelles in water. Triggered by H2O2, these micelles can be dissociated rapidly because hydrophobic thioether segments in their cores are oxidized into hydrophilic sulfoxide or sulfone groups. Additionally, the ROS produced by photosensitizer under light irradiation can also play the same role of H2O2. Such HBPMT micelles can be utilized to encapsulate anticancer drug paclitaxel (PTX) and photosensitizer chlorin e6 (Ce6) simultaneously for drug delivery and control release. The methyl thiazolyl tetrazolium assay toward MCF‐7 tumor cells (a human breast adenocarcinoma cell line) indicates that these micelles encapsulated with PTX and Ce6 exhibit a significant combinational efficacy of cell proliferation inhibition, which means the promising potential for synergistic chemo‐photodynamic cancer therapy. Such a novel nanocarrier based on amphiphilic to hydrophilic transition would provide a candidate for controlled drug release and cancer combination therapy. [ABSTRACT FROM AUTHOR]

A novel hybrid light-harvesting antenna with a srikaya-like structure of multi-graphene quantum dots (GQDs) as donors and one porphyrin unimolecular micelle as the acceptor was constructed through electrostatic self-assembly. The constructed antenna showed a high energy transfer efficiency of up to 93.6% and an antenna effect of 7.3 in an aqueous solution. [ABSTRACT FROM AUTHOR]

Amicelle-like hybrid natural-artificial light-harvesting nanosystem was prepared through protein-framed electrostatic self-assembly of phycocyanin and a four-armed porphyrin star polymer. The nanosystem has a special structure of pomegranate-like unimolecular micelle aggregate with one phycocyanin acceptor in the center and multiple porphyrin donors in the shell. It can inhibit donor self-quenching effectively and display efficient transfer of excitation energy (about 80.1%) in water. Furthermore, the number of donors contributing to a single acceptor could reach as high as about 179 in this nanosystem. [ABSTRACT FROM AUTHOR]

Hyperbranched multiarm copolymers (HMCs) have been shown to hold great potential as precursors in self-assembly, and many impressive supramolecular structures have been prepared through the self-assembly of HMCs in solution. However, theoretical studies on the corresponding self-assembly mechanism have been greatly lagging behind. Herein, we report the self-assembly of normal or reverse vesicles from amphiphilic HMCs by dissipative particle dynamics (DPD) simulation. The simulation disclosed both the self-assembly mechanisms and dynamics of vesicles. It indicates that the self-assembly of HMCs involves several steps, from randomly distributed unimolecular micelles to small spherical micelles, to membrane-like micelles, to finally small vesicles. The membranes are formed through the direct aggregation and lateral fusion of small micelles, and the bending and closing of the membranes give rise to small vesicles. Finally, large and steady vesicles are formed through the fusion of small vesicles. In addition, the bilayer or monolayer molecular packing modes as well as the mircrophase separation behaviors of HMCs in normal or reverse vesicles have also been studied. These simulation results explore details that cannot be observed in the experiments to a certain degree, and have extended the understanding of the vesicular self-assembly process of HMCs. [ABSTRACT FROM AUTHOR]

The macroscopic molecular self-assembly of an amphiphilic hyperbranched copolymer in acetone generated multiwalled tubes millimeters in diameter and centimeters in length. The thickness of the tube walls approaches 400 nanometers, and the walls have an inhomogeneous lamella structure that alternates between ordered hydrophilic domains and amorphous, partly irregular hydrophilic domains. [ABSTRACT FROM AUTHOR]

Abstract: A novel water-soluble copolyamide based on Nylon 66 was synthesized via solution-melt polycondensation of hexanedioic acid and sodium 5-sulfoisophthalate with 1,6-diaminohexane. The chemical structures of the products were ascertained by various spectroscopic techniques (FT-IR, Raman, and 1H NMR). The thermal properties of the polyamides under consideration were measured by TGA and DSC. According to the temperature dependence of FTIR spectra, it was found that the average strength of the intermolecular hydrogen bond of the water-soluble copolyamides becomes weak with increasing the temperature. It was found that the obtained random copolyamides could self-assemble into spherical micelles in aqueous solution with the size dependent on the hydrophilic fraction according to the DLS and TEM measurements. [Copyright &y& Elsevier]

Abstract: Polymeric micelles are recognized as very promising nanocarriers for small-molecule drugs, DNA, and proteins delivery. Polyphosphates are an important class of eminent biomaterials and widely used in biomedicine due to their good biocompatibility, biodegradability, and flexibility in adjusting the pendant structures. Here, some full-polyphosphate nanocarriers have been constructed successfully through self-assembly of amphiphilic hyperbranched multiarm copolymers (denoted as HPHEEP-star-PPEPs). The hydrophilic core and hydrophobic multiarm of HPHEEP-star-PPEPs are composed by hyperbranched and linear polyphosphates respectively. HPHEEP-star-PPEPs can self-assembly into nanocarriers in aqueous media with controlled size from 48 to 74nm by conveniently adjusting the length of hydrophobic arm. These nanocarriers possess excellent biocompatibility against NIH 3T3 cells and are easily internalized by vivid cells. Chlorambucil-loaded nanocarriers were investigated for proliferation inhibition of an MDA-MB-231 breast cancer cell line in vitro, and the chlorambucil dose required for 50% cellular growth inhibition was found to be 3μg/mL. [Copyright &y& Elsevier]

Abstract: A drug nanocarrier has been constructed through self-assembly of phospholipid analogous hyperbranched polymers (HPHEEP-alkyls) which contain a polar hyperbranched polyphosphate headgroup and many aliphatic tails. HPHEEP-alkyls were synthesized by self-condensing ring-opening polymerization of 2-(2-hydroxyethoxy)ethoxy-2-oxo-1,3,2-dioxaphospholane and then capped with palmitoyl chloride. Benefiting from the amphiphilic structure with the hydrophilic core and many hydrophobic tails, HPHEEP-alkyls were able to self-assemble into nanomicelles in aqueous media. Importantly, the size of the nanomicelles could be controlled conveniently from 98 to 215nm by adjusting the capped fraction of the hydroxyl groups with hydrophobic palmityls. The excellent biocompatibility of these nanomicelles was confirmed by methyl tetrazolium assay and acridine orange/ethidium bromide double staining against COS-7 cells. Confocal laser scanning microscopy and flow cytometry analysis demonstrated their good cell permeability, i.e. these nanomicelles were easily internalized by vivid cells and mainly located in the cytoplasm rather than nucleolus. Chlorambucil-loaded nanomicelles were investigated for proliferation inhibition of a MCF-7 breast cancer cell line in vitro, and the chlorambucil dose required for 50% cellular growth inhibition was found to be 5μg/mL. All of these results indicate that HPHEEP-alkyls nanomicelles can be used as safe and promising drug nanocarriers. [Copyright &y& Elsevier]

Abstract: A series of palmitoyl chloride-grafted hyperbranched polyglycerols were synthesized through cationic ring-opening polymerization and end-group modification. The obtained grafted copolymer of HPG-C16 possesses a hydrophilic hyperbranched polyether core and many hydrophobic alkyl arms, which shows interesting self-assembly behavior in THF and water. The results indicate that the copolymers with a relatively high alkyl grafting ratio can form unimolecular micelles in THF and will further assemble into giant vesicles around 1–10μm in THF/water mixed solvents. However, the HPG-C16 with a low alkyl grafting ratio of 15.6% can directly assemble into vesicles in THF and form micelles in water. [Copyright &y& Elsevier]