Dataset Information

Active Antioxidizing Particles for On-Demand Pressure-Driven Molecular Release.

ABSTRACT: Overproduced reactive oxygen species (ROS) are closely related to various health problems including inflammation, infection, and cancer. Abnormally high ROS levels can cause serious oxidative damage to biomolecules, cells, and tissues. A series of nano- or microsized particles has been developed to reduce the oxidative stress level by delivering antioxidant drugs. However, most systems are often plagued by slow molecular discharge, driven by diffusion. Herein, this study demonstrates the polymeric particles whose internal pressure can increase upon exposure to H2O2, one of the ROS, and in turn, discharge antioxidants actively. The on-demand pressurized particles are assembled by simultaneously encapsulating water-dispersible manganese oxide (MnO2) nanosheets and green tea derived epigallocatechin gallate (EGCG) molecules into a poly(lactic-co-glycolic acid) (PLGA) spherical shell. In the presence of H2O2, the MnO2 nanosheets in the PLGA particle generate oxygen gas by decomposing H2O2 and increase the internal pressure. The pressurized PLGA particles release antioxidative EGCG actively and, in turn, protect vascular and brain tissues from oxidative damage more effectively than the particles without MnO2 nanosheets. This H2O2 responsive, self-pressurizing particle system would be useful to deliver a wide array of molecular cargos in response to the oxidation level.

SUBMITTER: Seo Y

PROVIDER: S-EPMC7042956 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Active Antioxidizing Particles for On-Demand Pressure-Driven Molecular Release.

Seo Yongbeom Y Leong Jiayu J Teo Jye Yng JY Mitchell Jennifer W JW Gillette Martha U MU Han Bumsoo B Lee Jonghwi J Kong Hyunjoon H

ACS applied materials & interfaces 20171009 41

Overproduced reactive oxygen species (ROS) are closely related to various health problems including inflammation, infection, and cancer. Abnormally high ROS levels can cause serious oxidative damage to biomolecules, cells, and tissues. A series of nano- or microsized particles has been developed to reduce the oxidative stress level by delivering antioxidant drugs. However, most systems are often plagued by slow molecular discharge, driven by diffusion. Herein, this study demonstrates the polymer ...[more]

PMID: 28961399

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Project description:Stimuli-responsive, on-demand release of drugs from drug-eluting depots could transform the treatment of many local diseases, providing intricate control over local dosing. However, conventional on-demand drug release approaches rely on locally implanted drug depots, which become spent over time and cannot be refilled or reused without invasive procedures. New strategies to noninvasively refill drug-eluting depots followed by on-demand release could transform clinical therapy. Here we report an on-demand drug delivery paradigm that combines bioorthogonal click chemistry to locally enrich protodrugs at a prelabeled site and light-triggered drug release at the target tissue. This approach begins with introduction of the targetable depot through local injection of chemically reactive azide groups that anchor to the extracellular matrix. The anchored azide groups then capture blood-circulating protodrugs through bioorthogonal click chemistry. After local capture and retention, active drugs can be released through external light irradiation. In this report, a photoresponsive protodrug was constructed consisting of the chemotherapeutic doxorubicin (Dox), conjugated to dibenzocyclooctyne (DBCO) through a photocleavable ortho-nitrobenzyl linker. The protodrug exhibited excellent on-demand light-triggered Dox release properties and light-mediated in vitro cytotoxicity in U87 glioblastoma cell lines. Furthermore, in a live animal setting, azide depots formed in mice through intradermal injection of activated azide-NHS esters. After i.v. administration, the protodrug was captured by the azide depots with intricate local specificity, which could be increased with multiple refills. Finally, doxorubicin could be released from the depot upon light irradiation. Multiple rounds of depot refilling and light-mediated release of active drug were accomplished, indicating that this system has the potential for multiple rounds of treatment. Taken together, these in vitro and in vivo proof of concept studies establish a novel method for in vivo targeting and on-demand delivery of cytotoxic drugs at target tissues.

Dataset Information

Active Antioxidizing Particles for On-Demand Pressure-Driven Molecular Release.

Publications

Active Antioxidizing Particles for On-Demand Pressure-Driven Molecular Release.

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