Light triggering goldsomes enable local NO-generation and alleviate pathological vasoconstriction

I-Ju Lee; Po-Tsung Kao; Shao-An Hung; Zih-Wun Wang; Hui-Jen Lin; Wei-Tien Chang; Chen-Sheng Yeh; Ian Liau

doi:10.1016/j.nano.2020.102282

Light triggering goldsomes enable local NO-generation and alleviate pathological vasoconstriction

Nanomedicine. 2020 Nov:30:102282. doi: 10.1016/j.nano.2020.102282. Epub 2020 Aug 6.

Authors

I-Ju Lee¹, Po-Tsung Kao², Shao-An Hung¹, Zih-Wun Wang¹, Hui-Jen Lin¹, Wei-Tien Chang³, Chen-Sheng Yeh⁴, Ian Liau⁵

Affiliations

¹ Department of Applied Chemistry, National Chiao Tung University, Hsinchu, Taiwan.
² Department of Chemistry, National Cheng Kung University, Tainan, Taiwan.
³ Department of Emergency Medicine and Cardiovascular Center, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
⁴ Department of Chemistry, National Cheng Kung University, Tainan, Taiwan. Electronic address: csyeh@mail.ncku.edu.tw.
⁵ Department of Applied Chemistry, National Chiao Tung University, Hsinchu, Taiwan; Center for Emergent Functional Matter Science, National Chiao Tung University, Hsinchu, Taiwan. Electronic address: ianliau@mail.nctu.edu.tw.

PMID: 32771420
DOI: 10.1016/j.nano.2020.102282

Abstract

While nitric oxide (NO) can remedy vasoconstriction, inhalation of NO may cause systematic toxicity. We report a goldsome, which comprises a hollowed poly(lactic-co-glycolic acid) (PLGA) polymersome with S-nitrosoglutathione (GSNO, a NO donor) molecules and gold nanoparticles (Au NPs) incorporated in its hydrophilic core and hydrophobic membrane, respectively. Photothermal heating caused breakdown of polymersomes and enabled NO generation through reaction between GSNO and Au NPs. Photo-illumination at the zebrafish head led to local NO generation and selective cerebral vasodilation while it had little effects in regions away from the illumination site, and effectively mitigated hypoxia induced cerebral vasoconstriction. We demonstrate a translational potential by showing photo-stimulated NO generation with a clinical intravascular optical catheter. In conclusion, the goldsome, which enables light stimulated local NO generation and can be delivered with clinical intravascular optical catheters, should extend applications of NO therapies while surmounting limitations associated with systemic administration.

Keywords: Hypoxia; Intravascular optical catheter; Nitric oxide; Vasoconstriction; Zebrafish.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Gold / chemistry*
Hydrophobic and Hydrophilic Interactions
Light*
Metal Nanoparticles / chemistry*
Metal Nanoparticles / toxicity
Nitric Oxide / biosynthesis*
Nitric Oxide Donors / chemistry
Nitric Oxide Donors / pharmacology
Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
S-Nitrosoglutathione / chemistry
Vasoconstriction / drug effects*
Zebrafish / embryology

Substances

Nitric Oxide Donors
Polylactic Acid-Polyglycolic Acid Copolymer
Nitric Oxide
S-Nitrosoglutathione
Gold