Cong Chang

Galactosylated fluorescent labeled micelles as a liver targeting drug carrier

Galactosylated and fluorescein isothiocyanate (FITC) labeled polycaprolactone-g-dextran (Gal-PCL-g-Dex-FITC) polymers were synthesized. The grafted polymers can self-assemble into stable micelles in aqueous medium and in serum. Transmission electron microscopy (TEM) images showed that the self-assembled micelles were regularly spherical in shape. Micelle size determined by size analysis was around 120 nm. The anti-inflammation drug prednisone acetate as a model drug was loaded in the polymeric micelles, and the in vitro drug release was investigated. The galactosylated micelles could be selectively recognized by HepG2 cells and subsequently accumulate in HepG2 cells. The in vivo study demonstrated the relative uptake of the micelles by liver is much higher than the other tissues, indicating that the galactosylated micelles have great potential as a liver targeting drug carrier.

Synthesis and Applications of Shell Cross-Linked Thermoresponsive Hybrid Micelles Based on Poly(N-isopropylacrylamide-co-3-(trimethoxysilyl)propyl methacrylate)-b-poly(methyl methacrylate)

Shell cross-linked (SCL) thermoresponsive hybrid micelles consisting of a cross-linked thermoresponsive hybrid hydrophilic shell and a hydrophobic core domain were synthesized from poly(N-isopropylacrylamide-co-3- (trimethoxysilyl)propyl methacrylate)-b-polymethyl methacrylate (P(NIPAAm-co-MPMA)-b-PMMA) amphiphilic block copolymers. Transmission electron microscopy (TEM) images showed that the SCL micelles formed regularly globular nanoparticles. The SCL micelles showed reversible dispersion/aggregation in response to temperature cycles through an outer polymer shell lower critical solution temperature (LCST) for PNIPAAm at around 33 degrees C, observed by turbidity measurements and dynamic light scattering (DLS). The drug loading and in vitro drug release properties of the SCL micelles bearing a silica-reinforced PNIPAAm shell were further studied, which showed that the SCL micelles exhibited a much improved entrapment efficiency (EE) as well as a slower release rate which allowed the entrapped molecules to be slowly released over a much longer period of time as compared with pure PNIPAAm-b-PMMA micelles.

Dual targeting of a thermosensitive nanogel conjugated with transferrin and RGD-containing peptide for effective cell uptake and drug release

In this paper, both arginine-glycine-aspartic acid (RGD)-containing peptide and transferrin (Tf) were conjugated to the thermosensitive poly(N-isopropylacrylamide-co-propyl acrylic acid) (poly(NIPAAm-co-PAAc)) nanogel to prepare a dual-targeting drug carrier. The obtained nanogel was characterized in terms of fluorescence spectroscopy, UV-vis spectroscopy, dynamic light scattering (DLS) and transmission electron microscopy (TEM). In order to track the dual-ligand conjugated nanogel, fluorescein isothiocyanate (FITC) was further conjugated to the nanogel. A cell internalization experiment showed that the dual-ligand conjugated nanogel exhibited obviously enhanced endocytosis by HeLa cells as compared with non-tumorous cells (COS-7 cells). The drug-loaded dual-ligand conjugated nanogel could be transported efficiently into the target tumor cells and the anti-tumor effect was enhanced significantly, suggesting that the dual-ligand conjugated nanogel has great potential as a tumor targeting drug carrier.

Functionalized Thermoresponsive Micelles Self-Assembled from Biotin-PEG-b-P(NIPAAm-co-HMAAm)-b-PMMA for Tumor Cell Target

Novel micelles, comprising hydrophilic PEG shells, hydrophobic PMMA cores, and thermosensitive P(NIPAAm-co-HMAAm) segments were self-assembled from the biotin-PEG-b-P(NIPAAm-co-HMAAm)-b-PMMA triblock copolymer. The thermosensitive micelles exhibited superior stability and showed thermotriggered drug release behavior upon temperature alterations. The fluorescence spectroscopy and confocal microscopy studies confirmed that the self-assembled biotinylated micelles can be specifically and efficiently bonded to cancer cells with the administration of biotin-transferrin, suggesting that the multifunctional micelles have great potential as drug carriers for tumor targeting chemotherapy.

Porphyrin and Galactosyl Conjugated Micelles for Targeting Photodynamic Therapy

PurposeTo study the targeting and photodynamic therapy efficiency of porphyrin and galactosyl conjugated micelles based on amphiphilic copolymer galactosyl and mono-aminoporphyrin (APP) incoporated poly(2-aminoethyl methacrylate)-polycaprolactone (Gal-APP-PAEMA-PCL).MethodsPoly(2-aminoethyl methacrylate)-polycaprolactone (PAEMA-PCL) was synthesized by the combination of ring opening polymerization and reversible addition-fragmentation chain transfer (RAFT) polymerization, and then Gal-APP-PAEMA-PCL was obtained after conjugation of lactobionic acid and 5-(4-aminophenyl)-10,15,20-triphenylporphyrin (APP) to PAEMA-PCL. The chemical structures of the copolymers were characterized, and their biological properties were evaluated in human laryngeal carcinoma (HEp2) and human hepatocellular liver carcinoma (HepG2) cells.ResultsBoth APP-PAEMA-PCL and Gal-APP-PAEMA-PCL did not exhibit dark cytotoxicity to HEp2 cells and HepG2 cells. However, Gal-APP-PAEMA-PCL was taken up selectively by HepG2 cells and had the higher phototoxicity effect. Both polymers preferentially localized within cellular vesicles that correlated to the lysosomes.ConclusionsThe results indicated that porphyrin and galactosyl conjugated polymer micelles exhibited higher targeting and photodynamic therapy efficacy in HepG2 cells than in HEp2 cells.

Thermo-responsive shell cross-linked PMMA-b-P(NIPAAm-co-NAS) micelles for drug delivery.

Thermo-responsive amphiphilic poly(methyl methacrylate)-b-poly(N-isopropylacrylamide-co-N-acryloxysuccinimide) (PMMA-b-P(NIPAAm-co-NAS)) block copolymer was synthesized by successive RAFT polymerizations. The uncross-linked micelles were facilely prepared by directly dissolving the block copolymer in an aqueous medium, and the shell cross-linked (SCL) micelles were further fabricated by the addition of ethylenediamine as a di-functional cross-linker into the micellar solution. Optical absorption measurements showed that the LCST of uncross-linked and cross-linked micelles was 31.0°C and 40.8°C, respectively. Transmission electron microscopy (TEM) showed that both uncross-linked and cross-linked micelles exhibited well-defined spherical shape in aqueous phase at room temperature, while the SCL micelles were able to retain the spherical shape with relatively smaller dimension even at 40°C due to the cross-linked structure. In vitro drug release study demonstrated a slower and more sustained drug release behavior from the SCL micelles at high temperature as compared with the release profile of uncross-linked micelles, indicating the great potential of SCL micelles developed herein as novel smart carriers for controlled drug release.

Fabrication of a novel pH-sensitive glutaraldehyde cross-linked pectin nanogel for drug delivery

A novel pH-sensitive nanogel based on pectin cross-linked with glutaraldehyde (PT-GA) was designed and synthesized for drug delivery. Transmission electron microscope observation shows that the nano-sized gel particles exhibit a spherical morphology. The optical absorbance study of nanogel suspension reveals its pH sensitivity. Cytotoxicity study shows that the nanogel has no apparent inhibitory effect on cells. The in vitro drug-release behavior of the drug-loaded nanogel particles in three kinds of media, i.e., simulated gastric fluid, simulated intestine fluid and simulated colon fluid, was studied. PT-GA nanogel exhibits a faster release at a high pH, and the release could be further accelerated in the presence of pectinolytic enzyme, indicating that the nanogel may be used for colon-specific drug delivery.

Construction of mixed micelle with cross-linked core and dual responsive shells

A core cross-linked (CCL) mixed micelle with dual responsive shells was constructed from two amphiphilic block copolymers poly(methyl methacrylate-co-3-(trimethoxysilyl)propyl methacrylate)-b- poly(N-isopropylacrylamide) (P(MMA-co-MPMA)-b-PNIPAAm) and P(MMA-co-MPMA)-b-poly(2-(diethylamino)ethyl methacrylate) (P(MMA-co-MPMA)-b-PDEA) via a two-step process: cooperative aggregation of the two block copolymers into core-shell mixed micelles in acidic aqueous solution at room temperature followed by cross-linking of the hydrophobic core via an acid-catalyzed sol–gel process. The reversibly structural transformation of the core-shell mixed micelles into core-shell-corona (CSC) mixed micelles took place when subjected to elevated temperature or pH value, that is, high temperature resulted in the fabrication of CSC mixed micelle with shrunk PNIPAAm chains as the inner shell and stretched PDEA chains as the outer corona, and alkaline pH led to the formation of CSC mixed micelle with collapsed PDEA chains as the inner shell and extended PNIPAAm chains as the outer corona. Due to the existence of thermo- and pH- dually responsive shells, the structurally stable CCL mixed micelle may find practical applications in biomedical fields such as drug delivery and intelligent release.