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Self-assembled micelles of amphiphilic PEGylated rapamycin for loading paclitaxel and resisting multidrug resistant cancer cells†Electronic supplementary information (ESI) available: Chemicals and reagents, detailed experimental procedures for materials synthesis, characterization, cellular evaluations and supporting figures and tables. See DOI: 10.1039/c4tb01633eClick here for additional data file.

ABSTRACT: Self-assembled micelles of amphiphilic PEG-rapamycin conjugates loaded with paclitaxel have been developed for co-delivery and simultaneous intracellular release of paclitaxel and rapamycin, bypassing the cancer cell drug resistant mechanism and maximising the synergy of dual-drug combinational therapy. This novel nanomedicine offers 20-fold improved potency over free paclitaxel against a model multidrug resistant human breast cancer cell.

SUBMITTER: Tian W

PROVIDER: S-EPMC4324122 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Self-assembled micelles of amphiphilic PEGylated rapamycin for loading paclitaxel and resisting multidrug resistant cancer cells†Electronic supplementary information (ESI) available: Chemicals and reagents, detailed experimental procedures for materials synthesis, characterization, cellular evaluations and supporting figures and tables. See DOI: 10.1039/c4tb01633eClick here for additional data file.

Tian Wei W Liu Jieying J Guo Yuan Y Shen Yuanyuan Y Zhou Dejian D Guo Shengrong S

Journal of materials chemistry. B 20150127 7

Self-assembled micelles of amphiphilic PEG-rapamycin conjugates loaded with paclitaxel have been developed for co-delivery and simultaneous intracellular release of paclitaxel and rapamycin, bypassing the cancer cell drug resistant mechanism and maximising the synergy of dual-drug combinational therapy. This novel nanomedicine offers 20-fold improved potency over free paclitaxel against a model multidrug resistant human breast cancer cell. ...[more]

PMID: 25717377

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Project description:Thiol-ene 'click' chemistries have been widely used in biomaterials applications, including drug delivery, tissue engineering, and controlled cell culture, owing to their rapid, cytocompatible, and often orthogonal reactivity. In particular, hydrogel-based biomaterials formed by photoinitiated thiol-ene reactions afford spatiotemporal control over the biochemical and biomechanical properties of the network for creating synthetic materials that mimic the extracellular matrix or enable controlled drug release. However, the use of charged peptides functionalized with cysteines, which can form disulfides prior to reaction, and vinyl monomers that require multistep syntheses and contain ester bonds, may lead to undesired inhomogeneity or degradation under cell culture conditions. Here, we designed a thiol-ene hydrogel formed by the reaction of allyloxycarbonyl-functionalized peptides and thiol-functionalized poly(ethylene glycol). Hydrogels were polymerized by free radical initiation under cytocompatible doses of long wavelength ultraviolet light in the presence of water-soluble photoinitiators (lithium acylphosphinate, LAP, and 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl-1-propanone, Irgacure 2959). Mechanical properties of these hydrogels were controlled by varying the monomer concentration to mimic a range of soft tissue environments, and hydrogel stability in cell culture medium was observed over weeks. Patterns of biochemical cues were created within the hydrogels post-formation and confirmed through the incorporation of fluorescently-labeled peptides and Ellman's assay to detect free thiols. Human mesenchymal stem cells remained viable after encapsulation and subsequent photopatterning, demonstrating the utility of the monomers and hydrogels for three-dimensional cell culture. This facile approach enables the formation and characterization of hydrogels with well-defined, spatially-specific properties and expands the suite of monomers available for three-dimensional cell culture and other biological applications.

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