Issue

Vol. 13 (2021)

Mitochondrial H2Sn-Mediated Anti-Inflammatory Theranostics

https://doi.org/10.1007/s40820-021-00689-1
Won Young Kim
Department of Chemistry, Korea University, Seoul 02841, Korea
Miae Won
Department of Chemistry, Korea University, Seoul 02841, Korea
Seyoung Koo
Department of Chemistry, Korea University, Seoul 02841, Korea
Xingcai Zhang
John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA
Jong Seung Kim
Department of Chemistry, Korea University, Seoul 02841, Korea

Corresponding Author: Jong Seung Kim

jongskim@korea.ac.kr

Nano-Micro Letters, Vol. 13 (2021), Article Number: 168

Abstract

The insistent demand for space-controllable delivery, which reduces the side effects of non-steroidal anti-inflammatory drugs (NSAIDs), has led to the development of a new theranostics-based approach for anti-inflammatory therapy. The current anti-inflammatory treatments can be improved by designing a drug delivery system responsive to the inflammatory site biomarker, hydrogen polysulfide (H2Sn). Here, we report a novel theranostic agent 1 (TA1), consisting of three parts: H2Sn-mediated triggering part, a two-photon fluorophore bearing mitochondria targeting unit (Rhodol-TPP), and anti-inflammatory COX inhibitor (indomethacin). In vitro experiments showed that TA1 selectively reacts with H2Sn to concomitantly release both Rhodol-TPP and indomethacin. Confocal-microscopy imaging of inflammation-induced live cells suggested that TA1 is localized in the mitochondria where the H2Sn is overexpressed. The TA1 reacted with H2Sn in the endogenous and exogenous H2Sn environments and in lipopolysaccharide treated inflammatory cells. Moreover, TA1 suppressed COX-2 level in the inflammatory-induced cells and prostaglandin E2 (PGE2) level in blood serum from inflammation-induced mouse models. In vivo experiments with inflammation-induced mouse models suggested that TA1 exhibits inflammation-site-elective drug release followed by significant therapeutic effects, showing its function as a theranostic agent, capable of both anti-inflammatory therapy and precise diagnosis. Theranostic behavior of TA1 is highly applicable in vivo model therapeutics for the inflammatory disease.


Highlights:


1 Theranostic agent 1 (TA1) was successfully developed to provide dual functions: anti-inflammatory therapy and precise diagnosis.
2 TA1 selectively reacts with H2Sn in the mitochondria in response to inflammatory reactions to simultaneously produce both indomethacin as a drug and ring-opened fluorescence-on Rhodol.
3 Theranostic behavior of TA1 was proven by in vitro and in vivo imaging.
4 TA1 reveals inflammatory site-selective drug release followed by significant therapeutic effects and is highly applicable in vivo model therapeutics for the inflammatory disease.

Keywords

Theranostics Anti-inflammation Mitochondria Hydrogen polysulfides
Kim, Won Young, Miae Won, Seyoung Koo, Xingcai Zhang, and Jong Seung Kim. 2021. “Mitochondrial H2Sn-Mediated Anti-Inflammatory Theranostics”. Nano-Micro Letters 13 (August):168. https://doi.org/10.1007/s40820-021-00689-1.
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