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Photoswitchable nanoparticles for triggered tissue penetration and drug delivery.

ABSTRACT: We report a novel nanoparticulate drug delivery system that undergoes reversible volume change from 150 to 40 nm upon phototriggering with UV light. The volume change of these monodisperse nanoparticles comprising spiropyran, which undergoes reversible photoisomerization, and PEGylated lipid enables repetitive dosing from a single administration and enhances tissue penetration. The photoswitching allows particles to fluoresce and release drugs inside cells when illuminated with UV light. The mechanism of the light-induced size switching and triggered-release is studied. These particles provide spatiotemporal control of drug release and enhanced tissue penetration, useful properties in many disease states including cancer.

SUBMITTER: Tong R

PROVIDER: S-EPMC3363369 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Photoswitchable nanoparticles for triggered tissue penetration and drug delivery.

Tong Rong R Hemmati Houman D HD Langer Robert R Kohane Daniel S DS

Journal of the American Chemical Society 20120316 21

We report a novel nanoparticulate drug delivery system that undergoes reversible volume change from 150 to 40 nm upon phototriggering with UV light. The volume change of these monodisperse nanoparticles comprising spiropyran, which undergoes reversible photoisomerization, and PEGylated lipid enables repetitive dosing from a single administration and enhances tissue penetration. The photoswitching allows particles to fluoresce and release drugs inside cells when illuminated with UV light. The mec ...[more]

PMID: 22385538

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Project description:One of the challenges in designing a successful drug-delivery vehicle is the control over drug release. Toward this, a number of multifunctional nanoparticles with multiple triggers and complex chemistries have been developed. To achieve an efficient and maximum therapeutic effect, a trigger dependent drug-delivery system with sustained release is desirable. In this paper, we report the use of a combination of thermoresponsive gold core and polymeric shell nanoparticles that can provide a sustained, triggered release of doxorubicin, making the system more efficient compared to individual nanoparticles. The selection of the system was dependent on the best trigger applicable in biological systems and a component responsive to that trigger. Because of the best tissue penetration depth observed for radiofrequency (rf), we chose rf as a trigger. Whereas the gold nanoparticles (AuNPs) provided hyperthermia trigger on exposure to rf fields, the thermoresponsiveness was endowed by poly(N-isopropylacrylamide) (pNIPAm)-based polymer shells. AuNPs with three different compositions of shells, only pNIPAm and p(NIPAm-co-NIPMAm) with the ratio of NIPAm/N-(isopropylmethacrylamide) (NIPMAm) 1:1 (pNIPMAm50) and 1:3 (pNIPMAm75), were synthesized. We observed that the polymer coating on the AuNPs did not affect the heating efficiency of AuNPs by rf and exhibited a temperature-dependent release of the chemotherapeutic drug, doxorubicin. The nanoparticles were biocompatible, stable in biologically relevant media, and were able to show a burst as well as a sustained release, which was rf-dependent. Interestingly, we observed that when HeLa cells were treated with doxorubicin-loaded gold core-polymeric shell NPs and exposed to rf for varying times, the mixture of the two polymeric shell nanoparticles induced more cell death as compared to the cells treated with single nanoparticles, suggesting that such multi-nanoparticle systems can be more efficacious delivery systems instead of a single multicomponent system.

Dataset Information

Photoswitchable nanoparticles for triggered tissue penetration and drug delivery.

Publications

Photoswitchable nanoparticles for triggered tissue penetration and drug delivery.

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