Chaojian Chen

Photo-responsive, biocompatible polymeric micelles self-assembled from hyperbranched polyphosphate-based polymers

Photo-responsive biocompatible micelles were constructed from amphiphilic hyperbranched polyphosphate based polymer (denoted as HPHEEP-DNQ) and applied in the controlled release of coumarin 102. HPHEEP-DNQ was designed and synthesized by modification of hydrophilic hyperbranched polyphosphate (HPHEEP) with hydrophobic, light-responsive 2-diazo-1,2-naphthoquinone (DNQ) molecules. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) measurements revealed that the polymer can self-assemble into spherical micelles with an average diameter of about 186 nm in aqueous solution. The critical micelle concentration (CMC) of the micelles was 0.025 mg mL−1 determined by fluorescence spectroscopy using Nile Red as a fluorescence probe. By illuminating the micelles with 365 nm UV light, light triggered destabilization procedure was investigated by TEM and DLS. In addition, model drug coumarin 102 was successfully encapsulated into the micelles and the controlled release behavior under 365 nm UV light was investigated by fluorescence spectroscopy. Cell viability tests against two types of cells indicated that the micelles have excellent biocompatibility. These photo-responsive and biocompatible polymeric micelles self-assembled from hyperbranched polyphosphate based polymer might have great potential as smart carriers in the field of drug delivery.

Biocompatible vesicles based on PEO-b-PMPC/α-cyclodextrin inclusion complexes for drug delivery

Poly(ethylene oxide) (PEO) and poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) are biocompatible polymers that have delivered clinically proven benefits in various biomedical applications. Biocompatible polymer vesicles were prepared on basis of the inclusion complexation between α-cyclodextrins (α-CDs) and double-hydrophilic poly(ethylene oxide)-b-poly(2-methacryloyloxyethyl phosphorylcholine) (PEO-b-PMPC) in aqueous media without using organic solvent. The supramolecular structure of the nano-sized vesicles was demonstrated by transmission electron microscopy (TEM), atomic force microscopy (AFM) and dynamic light scattering (DLS). The biocompatibility of PEO-b-PMPC block copolymers and PEO-b-PMPC/α-CDs vesicles were studied by cell viability test, and the results revealed that both of them showed excellent cytocompatibility. Hydrophilic doxorubicin (DOX·HCl) was successfully loaded into the vesicle with loading content of 10.3% and loading efficiency of 30%. The DOX·HCl loaded vesicles showed lower cytotoxicity than free drugs, and could efficiently deliver and release the drug into HepG2 cells as confirmed by fluorescence microscope (FM). With these properties, the polymer vesicles are attractive as drug carriers for pharmaceutical applications.

Biocompatible and biodegradable polymersomes as delivery vehicles in biomedical applications

Biocompatible and biodegradable polymersomes are commonly self-assembled from amphiphilic diblock copolymers composed of hydrophilic poly(ethylene glycol) (PEG) or poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) segments and hydrophobic polyester blocks, such as poly(lactic acid) (PLA) or poly(e-caprolactone) (PCL). Such polymersomes have emerged as promising delivery vehicles for pharmaceutical applications. Presented in this review are summaries of recent developments of biocompatible and biodegradable polymersomes, including self-assembly, encapsulation of various therapeutics, pH-induced hydrolysis for controlled release as well as their functionalization and intelligent design.

Near-infrared light-sensitive micelles for enhanced intracellular drug delivery

Near-infrared light-sensitive polymeric micelles were prepared for the enhanced intracellular delivery of doxorubicin (DOX). The micelles were prepared from dextran-graft-(2-diazo-1,2-naphthoquinone) (Dex-DNQ) amphiphilic copolymers which were synthesized by modification of hydrophilic dextran with hydrophobic DNQ molecules. The hydrophobic DNQ molecule is an attractive photo-trigger group because its UV/NIR-induced Wolff rearrangement can result in a drastic change into a hydrophilic 3-indenecarboxylic acid (3-IC) molecule with pKa of 4.5. Thus, under UV or NIR irradiation, Dex-DNQ micelles will rapidly release encapsulated drugs due to the micelle dissociation. DOX was chosen as an anticancer drug to be encapsulated into the Dex-DNQ micelle with the loading efficiency and content of 60% and 24%, respectively. In vitro cell viability studies, the micelles exhibited higher intracellular DOX release under NIR irradiation at 808 nm, which resulted in significant growth inhibition of HepG2 cancer cells. Fluorescence microscopy and flow cytometry further proved the enhanced intracellular drug release behaviour of DOX-loaded Dex-DNQ micelles under NIR irradiation. We are convinced that this smart drug nanocarrier is potentially useful for cancer chemotherapy.

Biocompatible Micelles Based on Comb-like PEG Derivates: Formation, Characterization, and Photo-responsiveness

A novel comb-like derivative CPEG-g-DNQ was prepared by incorporating light responsive 2-diazo-1,2-naphthoquinone (DNQ) groups into the structure of comb-like poly(ethylene glycol) (CPEG). DLS and TEM results showed that CPEG-g-DNQ self-assembled into spherical micelles with an average size of about 135 nm in water. Upon exposure to light, the micelles could be disrupted because of the conversion of hydrophobic DNQ to hydrophilic 3-indenecarboylic acid. Additionally, hydrophobic coumarin 102 was successfully loaded into the micelles and photo-induced ON-OFF release was demonstrated by fluorescence spectroscopy. MTT assay revealed that the micelles are biocompatible. These photo-responsive micelles might have great potential for controlled release of hydrophobic drugs.

Biocompatible and biodegradable polymersomes for pH-triggered drug release

Nano-sized biocompatible and biodegradable polymersomes were prepared based on poly(D,L-lactide)-block-poly(2-methacryloyloxyethyl phosphorylcholine) (PLA-b-PMPC) diblock copolymers and applied for the release anti-cancer drugs. Hydrophobic doxorubicin (DOX) and hydrophilic doxorubicin hydrochloride (DOX·HCl) were successfully loaded into the polymersome membrane and polymersome interior, respectively. The in vitro release studies demonstrated that the release of DOX and DOX·HCl from polymersomes was highly pH-dependent, i.e. significantly faster drug release at mildly acidic pH of 5.0 compared to physiological pH 7.4. Furthermore, DOX·HCl-loaded polymersomes exhibited faster drug release than DOX-loaded polymersomes under the same pH conditions. The highly pH-depended release behavior was attributed to the hydrolysis of PLA-b-PMPC, which would result in morphological transformation from polymersome to micelle with a triggered release of the encapsulated drugs. The drug-loaded polymersomes were shown to rapidly enter HepG2 cells, localize in their endosome/lysosomes with acidic pH environment and display enhanced intracellular release of the drugs into the cytosol. These biocompatible and acid pH-sensitive polymersomes might have great potential for cancer therapy.

Construction of photo-responsive micelles from azobenzene-modified hyperbranched polyphosphates and study of their reversible self-assembly and disassembly behaviours

Photo-responsive micelles with reversible self-assembly and disassembly behaviours were constructed via the supramolecular host–guest interaction of β-cyclodextrin (β-CD) and an amphiphilic azobenzene-containing hyperbranched polymer (denoted HPHEEP-Azo). The polymer was prepared through the carboxylation of hydroxyl groups in hyperbranched polyphosphate (HPHEEP-OH) with succinic anhydride and the subsequent esterification reaction with 4-hydroxyazobenzene. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) measurements reveal that HPHEEP-Azo can self-assemble into spherical micelles with an average diameter of 169.9 nm in aqueous solution. The critical micelle concentration (CMC) of the micelles is 0.013 mg mL−1. After addition of β-CD into the micellar solution, the micelles dissociated gradually upon increasing the addition amount of β-CD. Irradiation experiments show that reversible self-assembly and disassembly behaviours can be controlled by irradiating with UV and visible light. These photo-responsive micelles self-assembled from hyperbranched polymers might have great potential in various practical applications such as controlled drug release.

Fabrication of dual-responsive micelles based on the supramolecular interaction of cucurbit[8]uril

Biocompatible and dual-responsive micelles were fabricated from a cucurbit[8]uril (CB[8]) connected amphiphilic linear-hyperbranched polymer complex. After addition of adamantaneamine or Na2S2O4, the micelles became larger and exhibited triggered-release of hydrophobic coumarin 102 because of the CB[8]-based host–guest interaction.

Biomimetic Polymersomes as Carriers for Hydrophilic Quantum Dots

For polymersomes to achieve their potential as effective delivery vehicles, they must efficiently encapsulate therapeutic agents into either the aqueous interior or the hydrophobic membrane. In this study, cell membrane-mimetic polymersomes were prepared from amphiphilic poly(D,L-lactide)-b-poly(2-methacryloyloxyethylphosphorylcholine) (PLA-b-PMPC) diblock copolymers and were used as encapsulation devices for water-soluble molecules. Thioalkylated zwitterionic phosphorylcholine protected quantum dots (PC@QDs) were chosen as hydrophilic model substrates and successfully encapsulated into the aqueous polymersome interior, as evidenced by transmission electron microscopy (TEM) and flow cytometry. In addition, we also found a fraction of the PC@QDs were bound to both the external and internal surfaces of the polymersome. This interesting immobilization might be due to the ion-pair interactions between the phosphorylcholine groups on the PC@QDs and polymersomes. The experimental encapsulation results support a mechanism of PLA-b-PMPC polymersome formation in which PLA-b-PMPC copolymer chains first form spherical micelles, then worm-like micelles, and finally disk-like micelles which close up to form polymersomes.

Cucurbit[8]uril supramolecular assembly for positively charged ultrathin films as nanocontainers.

The design of positively charged ultrathin films for surface modification is of crucial importance for biomedical applications. Herein, we report the layer-by-layer assembly of pure positively charged ultrathin films based on the host-guest interaction of cucurbit[8]uril (CB[8]). Two positively charged poly(ethylenimine)s (PEI) functionalized with guest moieties methyl viologen (MV) and indole (ID) were alternately assembled with the formation of CB[8] ternary complex under basic conditions. The growth of the (PEI-MV@CB[8]/PEI-ID) films was monitored by spectroscopic ellipsometry and quartz crystal microbalance. The morphology and structure of the films were characterized by scanning electron microscopy and UV-vis spectroscopy, respectively. These positively charged (PEI-MV@CB[8]/PEI-ID) films were very stable in the pH range from 4 to 9 but disassembled immediately when subjected to a competitive guest adamantylamine. Finally, the films were successfully employed as nanocontainers for DNA loading and subsequent directing the transfection of the adhered cells.