Photo-responsive polymeric micelles and prodrugs: synthesis and characterization.

Bio-recognizable and photocleavable amphiphilic glycopolymers and prodrugs containing photodegradable linkers (i.e. 5-hydroxy-2-nitrobenzyl alcohol) as junction points between bio-recognizable hydrophilic glucose (or maltose) and hydrophobic poly(α-azo-ε-caprolactone)-grafted alkyne or drug chains were synthesized by combining ring-opening polymerization, nucleophilic substitution, and "click" post-functionalization with alkynyl-pyrene and 2-nitrobenzyl-functionalized indomethacin (IMC). The block-grafted glycocopolymers could self-assemble into spherical photoresponsive micelles with hydrodynamic sizes of <200 nm. Fluorescence emission measurements indicated the release of Nile red, a hydrophobic dye, encapsulated by the Glyco-ONB-P(αN3CL-g-alkyne) n micelles, in response to irradiation caused by micelle disruption. Light-triggered bursts were observed for IMC-loaded or -conjugated micelles during the first 5 h. Following light irradiation, the drug release rate of IMC-conjugated micelles was faster than that of IMC-loaded micelles. Selective lectin binding experiments confirmed that glycosylated Glyco-ONB-P(αN3CL-g-alkyne) n could be used in bio-recognition applications. The nano-prodrug with and without UV irradiation was associated with negligible levels of toxicity at concentrations of less than 30 µg mL-1. The confocal microscopy and flow cytometry results indicated that the uptake of doxorubicin (DOX)-loaded micelles with UV irradiation by HeLa cells was faster than without UV irradiation. The DOX-loaded Gluco-ONB-P(αN3CL-g-PONBIMC)10 micelles effectively inhibited HeLa cells' proliferation with a half-maximal inhibitory concentration of 8.8 µg mL-1.

Passive targeting of thermosensitive diblock copolymer micelles to the lungs: synthesis and characterization of poly(N-isopropylacrylamide)-block-poly(ε-caprolactone).

BACKGROUND: Amphiphilic poly(N-isopropylacrylamide)-block-poly(ε-caprolactone) (PNiPAAm-b-PCL) copolymers were synthesized by ring-opening polymerization to form thermosensitive micelles as nanocarriers for bioimaging and carboplatin delivery. RESULTS: The critical micelle concentration increased from 1.8 to 3.5 mg/l following the decrease of the PNiPAAm chain length. The copolymers revealed a lower critical solution temperature (LCST) between 33 and 40°C. The copolymers self-assembled to form spherical particles of 146-199 nm in diameter. Carboplatin in micelles exhibited a slower release at 37°C relative to that at 25°C due to the gel layer formation on the micellar shell above the LCST. The micelles containing dye or carboplatin were intravenously injected into the rats for in vivo bioimaging and drug biodistribution. The bioimaging profiles showed a significant accumulation of micelles in the lungs. The micelles could minimize the reticuloendothelial system (RES) recognition of the dye. In vivo biodistribution demonstrated an improved pulmonary accumulation of carboplatin from 2.5 to 3.4 µg/mg by the micelles as compared to the control solution. Carboplatin accumulation in the heart and kidneys was reduced after encapsulation by the micelles. CONCLUSION: This study supports the potential of PNiPAAm-b-PCL micelles to passively target the lungs and attenuate RES uptake and possible side effects.

Synthesis and characterization of amphiphilic photocleavable polymers based on dextran and substituted-ɛ-caprolactone.

In this study, we synthesized photocleavable amphiphilic block copolymers containing photodegradable linkers, 5-hydroxy-2-nitrobenzyl alcohol, as junction points between hydrophilic dextran (or maltodextrin) and hydrophobic poly(4-substituted-ɛ-caprolactone) chains, by using a combination of ring-opening polymerization and nucleophilic substitution reactions. When the polymer solutions were exposed to ultraviolet (UV) irradiation, major structural and morphological changes were observed in the particles. The copolymers were biodegradable and biocompatible, and they can self-assemble into spherical photoresponsive micelles. Fluorescence emission measurements indicated the release of Nile red, a hydrophobic dye, encapsulated by the Dex-ONB-PXCL micelles, in response to irradiation caused by the disruption of the micelles. Light-triggered bursts were observed for indomethacin (IMC)-loaded Dex-ONB-PXCL micelles during the first 5 h. The nanoparticles were associated with nonsignificant toxicity at concentrations of less than 100 µg mL(-1). The confocal microscopy and flow cytometry results showed that the uptake of DOX-loaded micelles by HeLa cells was slightly less than that of free DOX, and it was predominantly retained in the cytoplasm.

Amphiphilic polyesters bearing pendant sugar moieties: synthesis, characterization, and cellular uptake.

Ring-opening polymerization (ROP) and "click" reactions were used to prepare a series of amphiphilic block-graft (PαN3CL-g-Sugar)-b-PCL polymers. The glycosylated RO-(PαN3CL-g-Sugar)-b-PCL polymers formed micelles with critical micelle concentrations (CMCs) in the range of 4.9-23.2 mg L(-1) in the aqueous phase. The mean diameters of the micelles were between 21 nm and 125 nm, considerably lower than the 200 nm diameter at which the uptake of micelles by the reticuloendothelial cells becomes compromised. Selective lectin-binding experiments confirmed that glycosylated RO-(PαN3CL-g-Sugar)-b-PCL can be used in biorecognition applications, and in vitro cell-viability assay showed that RO-(PαN3CL-g-Sugar)-b-PCL has low cytotoxicity. Micelles loaded with doxorubicin (DOX) facilitated an improved uptake of DOX by HeLa cells that was completed within 1h, and the endocytosed-DOX successfully reached intracellular compartments and entered nuclei.

A colloidal suspension of nanostructured poly(N-butyl benzimidazole)-graphene sheets with high oxidase yield for analytical glucose and choline detections.

A colloidal suspension of nanostructured poly(N-butyl benzimidazole)-graphene sheets (PBBIns-Gs) was used to modify a gold electrode to form a three-dimensional PBBIns-Gs/Au electrode that was sensitive to hydrogen peroxide (H2O2) in the presence of acetic acid (AcOH). The positively charged nanostructured poly(N-butyl benzimidazole) (PBBIns) separated the graphene sheets (Gs) and kept them suspended in an aqueous solution. Additionally, graphene sheets (Gs) formed "diaphragms" that intercalated Gs, which separated PBBIns to prevent tight packing and enhanced the surface area. The PBBIns-Gs/Au electrode exhibited superior sensitivity toward H2O2 relative to the PBBIns-modified Au (PBBIns/Au) electrode. Furthermore, a high yield of glucose oxidase (GOD) on the PBBIns-Gs of 52.3mg GOD per 1mg PBBIns-Gs was obtained from the electrostatic attraction between the positively charged PBBIns-Gs and negatively charged GOD. The non-destructive immobilization of GOD on the surface of the PBBIns-Gs (GOD-PBBIns-Gs) retained 91.5% and 39.2% of bioactivity, respectively, relative to free GOD for the colloidal suspension of the GOD-PBBIns-Gs and its modified Au (GOD-PBBIns-Gs/Au) electrode. Based on advantages including a negative working potential, high sensitivity toward H2O2, and non-destructive immobilization, the proposed glucose biosensor based on an GOD-PBBIns-Gs/Au electrode exhibited a fast response time (5.6s), broad detection range (10µM to 10mM), high sensitivity (143.5µAmM(-1)cm(-2)) and selectivity, and excellent stability. Finally, a choline biosensor was developed by dipping a PBBIns-Gs/Au electrode into a choline oxidase (ChOx) solution for enzyme loading. The choline biosensor had a linear range of 0.1µM to 0.83mM, sensitivity of 494.9µAmM(-1)cm(-2), and detection limit of 0.02µM. The results of glucose and choline measurement indicate that the PBBIns-Gs/Au electrode provides a useful platform for the development of oxidase-based biosensors.