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Hydrogel-nanoparticle composites for optically modulated cancer therapeutic delivery.

ABSTRACT: A poly(N-isopropylacrylamide-co-acrylamide) (NIPAAm-co-AAm) hydrogel with near-infrared (NIR) absorbing silica-gold nanoshells was designed as a platform for pulsatile delivery of cancer therapeutics. This hydrogel was designed to have a lower critical solution temperature (LCST) above physiologic temperature, such that the material will transition from a hydrated state to a collapsed state above ~40°C. Additionally, the silica-gold nanoshells used were designed to have a peak extinction coefficient in the NIR, where penetration of light through tissue is maximal. This heat-triggered material phase transition of the composite was found to follow exposure of NIR light, indicating the ability of the NIR absorption by the nanoshells to sufficiently drive this transition. The composite material was loaded with either doxorubicin or a DNA duplex (a model nucleic acid therapeutic), two cancer therapeutics with differing physical and chemical properties. Release of both therapeutics was dramatically enhanced by NIR light exposure, causing 2-5x increase in drug release. Drug delivery profiles were influenced by both the molecular size of the drug as well as its chemical properties. The DNA therapeutic showed slower rates of nonspecific delivery by passive diffusion due to its larger size. Additionally, only 70% of the more hydrophobic doxorubicin was released from the material, whereas the more hydrophilic DNA showed over 90% release. Further, hydrogel composites were used to deliver the doxorubicin to CT.26-WT colon carcinoma cells, eliciting a therapeutic response. This work validates the potential application for this material in site-specific cancer therapeutic delivery.

SUBMITTER: Strong LE

PROVIDER: S-EPMC4077349 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Hydrogel-nanoparticle composites for optically modulated cancer therapeutic delivery.

Strong Laura E LE Dahotre Shreyas N SN West Jennifer L JL

Journal of controlled release : official journal of the Controlled Release Society 20140123

A poly(N-isopropylacrylamide-co-acrylamide) (NIPAAm-co-AAm) hydrogel with near-infrared (NIR) absorbing silica-gold nanoshells was designed as a platform for pulsatile delivery of cancer therapeutics. This hydrogel was designed to have a lower critical solution temperature (LCST) above physiologic temperature, such that the material will transition from a hydrated state to a collapsed state above ~40°C. Additionally, the silica-gold nanoshells used were designed to have a peak extinction coeffic ...[more]

PMID: 24462898

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Project description:Modulating fluorescent protein emission holds great potential for increasing readout sensitivity for applications in biological imaging and detection. Here, we identify and engineer optically modulated yellow fluorescent proteins (EYFP, originally 10C, but renamed EYFP later, and mVenus) to yield new emitters with distinct modulation profiles and unique, optically gated, delayed fluorescence. The parent YFPs are individually modulatable through secondary illumination, depopulating a long-lived dark state to dynamically increase fluorescence. A single point mutation introduced near the chromophore in each of these YFPs provides access to a second, even longer-lived modulatable dark state, while a different double mutant renders EYFP unmodulatable. The naturally occurring dark state in the parent YFPs yields strong fluorescence modulation upon long-wavelength-induced dark state depopulation, allowing selective detection at the frequency at which the long wavelength secondary laser is intensity modulated. Distinct from photoswitches, however, this near IR secondary coexcitation repumps the emissive S1 level from the long-lived triplet state, resulting in optically activated delayed fluorescence (OADF). This OADF results from secondary laser-induced, reverse intersystem crossing (RISC), producing additional nanosecond-lived, visible fluorescence that is delayed by many microseconds after the primary excitation has turned off. Mutation of the parent chromophore environment opens an additional modulation pathway that avoids the OADF-producing triplet state, resulting in a second, much longer-lived, modulatable dark state. These Optically Modulated and Optically Activated Delayed Fluorescent Proteins (OMFPs and OADFPs) are thus excellent for background- and reference-free, high sensitivity cellular imaging, but time-gated OADF offers a second modality for true background-free detection. Our combined structural and spectroscopic data not only gives additional mechanistic details for designing optically modulated fluorescent proteins but also provides the opportunity to distinguish similarly emitting OMFPs through OADF and through their unique modulation spectra.

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Hydrogel-nanoparticle composites for optically modulated cancer therapeutic delivery.

Publications

Hydrogel-nanoparticle composites for optically modulated cancer therapeutic delivery.

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