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Light-activated doxorubicin-encapsulated perfluorocarbon nanodroplets for on-demand drug delivery in an in vitro angiogenesis model: Comparison between perfluoropentane and perfluorohexane.

ABSTRACT: Phase-transition perfluorocarbon (PFC) nanodroplets have been developed for on-demand drug delivery carriers with external triggers such as ultrasound or laser irradiation techniques. Although various perfluorocarbons, including perfluoropentane (C₅F₁₂) and perfluorohexane (C₆F₁₄), have been investigated for their theranostic use, comparison of the phase-transition efficiency, the drug delivery efficacy by light activation, and physical properties of the PFC nanodroplets have not been reported. We have synthesized gold nanorod-coated doxorubicin-encapsulated perfluorocarbon nanodroplets using perfluoropentane and perfluorohexane as light-activated on-demand drug delivery carriers, called PF5 and PF6, respectively. When gold nanorods on the perfluorocarbon nanodroplets resonate with a laser wavelength, plasmonic heat generated on the gold nanorods vaporizes the nanodroplets to gas bubbles (phase-transition), and releases the encapsulated drug from the nanodroplet core. Overall, the nanodroplet size, drug encapsulation efficiency, number density, and cytotoxicity were similar between PF5 and PF6. However, the long-term stability against passive phase-transition or coalescence in physiological conditions and the phase-transition efficiency were different from each other. PF6 was better in long-term stability but showed lower phase-transition than PF5. The lower phase-transition of PF6 might have led to lower drug delivery efficiency compared to PF5. This is probably because PF6 has higher temperature thresholds required for phase-transition due to its higher boiling point. The study demonstrated feasibility of the light-activated nanodroplets for on-demand targeted nanotherapy, which suppresses the development of angiogenesis.

SUBMITTER: Yuan Z

PROVIDER: S-EPMC6881552 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Light-activated doxorubicin-encapsulated perfluorocarbon nanodroplets for on-demand drug delivery in an in vitro angiogenesis model: Comparison between perfluoropentane and perfluorohexane.

Yuan Zheng Z Demith Alec A Stoffel Ryan R Zhang Zhe Z Park Yoonjee C YC

Colloids and surfaces. B, Biointerfaces 20190907

Phase-transition perfluorocarbon (PFC) nanodroplets have been developed for on-demand drug delivery carriers with external triggers such as ultrasound or laser irradiation techniques. Although various perfluorocarbons, including perfluoropentane (C5F12) and perfluorohexane (C6F14), have been investigated for their theranostic use, comparison of the phase-transition efficiency, the drug delivery efficacy by light activation, and physical properties of t ...[more]

PMID: 31522023

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Project description:Nanoscale perfluorocarbon (PFC) droplets have enormous potential as clinical theranostic agents. They are biocompatible and are currently used in vivo as contrast agents for a variety of medical imaging modalities, including ultrasound, computed tomography, photoacoustic and 19F-magnetic resonance imaging. PFC nanodroplets can also carry molecular and nanoparticulate drugs and be activated in situ by ultrasound or light for targeted therapy. Recently, there has been renewed interest in using PFC nanodroplets for hypoxic tumor reoxygenation towards radiosensitization based on the high oxygen solubility of PFCs. Previous studies showed that tumor oxygenation using PFC agents only occurs in combination with enhanced oxygen breathing. However, recent studies suggest that PFC agents that accumulate in solid tumors can contribute to radiosensitization, presumably due to tumor reoxygenation without enhanced oxygen breathing. In this study, we quantify the impact of oxygenation due to PFC nanodroplet accumulation in tumors alone in comparison with other reoxygenation methodologies, in particular, carbogen breathing. Methods: Lipid-stabilized, PFC (i.e., perfluorooctyl bromide, CF3(CF2)7Br, PFOB) nanoscale droplets were synthesized and evaluated in xenograft prostate (DU145) tumors in male mice. Biodistribution assessment of the nanodroplets was achieved using a fluorescent lipophilic indocarbocyanine dye label (i.e., DiI dye) on the lipid shell in combination with fluorescence imaging in mice (n?3 per group). Hypoxia reduction in tumors was measured using PET imaging and a known hypoxia radiotracer, [18F]FAZA (n? 3 per group). Results: Lipid-stabilized nanoscale PFOB emulsions (mean diameter of ~250 nm), accumulated in the xenograft prostate tumors in mice 24 hours post-injection. In vivo PET imaging with [18F]FAZA showed that the accumulation of the PFOB nanodroplets in the tumor tissues alone significantly reduced tumor hypoxia, without enhanced oxygen (i.e., carbogen) breathing. This reoxygenation effect was found to be comparable with carbogen breathing alone. Conclusion: Accumulation of nanoscale PFOB agents in solid tumors alone successfully reoxygenated hypoxic tumors to levels comparable with carbogen breathing alone, an established tumor oxygenation method. This study confirms that PFC agents can be used to reoxygenate hypoxic tumors in addition to their current applications as multifunctional theranostic agents.

Dataset Information

Light-activated doxorubicin-encapsulated perfluorocarbon nanodroplets for on-demand drug delivery in an in vitro angiogenesis model: Comparison between perfluoropentane and perfluorohexane.

Publications

Light-activated doxorubicin-encapsulated perfluorocarbon nanodroplets for on-demand drug delivery in an in vitro angiogenesis model: Comparison between perfluoropentane and perfluorohexane.

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