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Kolygina, Diana
첨단연성물질 연구단
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Mixed-Charge Nanocarriers Allow for Selective Targeting of Mitochondria by Otherwise Nonselective Dyes

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Title
Mixed-Charge Nanocarriers Allow for Selective Targeting of Mitochondria by Otherwise Nonselective Dyes
Author(s)
Diana V. Kolygina; Marta Siek; Magdalena Borkowska; Guillermo Ahumada; Barski, Piotr; Witt, Dariusz; Ah-Young Jee; Han Miao; Juan Carlos Ahumada; Steve Granick; Kristiana Kandere-Grzybowska; Bartosz A. Grzybowski
Publication Date
2021-07
Journal
ACS NANO, v.15, no.7, pp.11470 - 11490
Publisher
American Chemical Society
Abstract
© 2021 American Chemical Society.Targeted delivery of molecular cargos to specific organelles is of paramount importance for developing precise and effective therapeutics and imaging probes. This work describes a disulfide-based delivery method in which mixed-charged nanoparticles traveling through the endolysosomal tract deliver noncovalently bound dye molecules selectively into mitochondria. This system comprises three elements: (1) The nanoparticles deliver their payloads by a kiss-and-go mechanism-that is, they drop off their dye cargos proximate to mitochondria but do not localize therein; (2) the dye molecules are by themselves nonspecific to any cellular structures but become so with the help of mixed-charge nanocarriers; and (3) the dye is engineered in such a way as to remain in mitochondria for a long time, up to days, allowing for observing dynamic remodeling of mitochondrial networks and long-term tracking of mitochondria even in dividing cells. The selectivity of delivery and long-lasting staining derive from the ability to engineer charge-imbalanced, mixed [+/-] on-particle monolayers and from the structural features of the cargo. Regarding the former, the balance of [+] and [-] ligands can be adjusted to limit cytotoxicity and control the number of dye molecules adsorbed onto the particles' surfaces. Regarding the latter, comparative studies with multiple dye derivatives we synthesized rationalize the importance of polar groups, long alkyl chains, and disulfide moieties in the assembly of fluorescent nanoconstructs and long-lasting staining of mitochondria. Overall, this strategy could be useful for delivering hydrophilic and/or anionic small-molecule drugs difficult to target to mitochondria by classical approaches.
URI
https://pr.ibs.re.kr/handle/8788114/10513
DOI
10.1021/acsnano.1c01232
ISSN
1936-0851
Appears in Collections:
Center for Soft and Living Matter(첨단연성물질 연구단) > 1. Journal Papers (저널논문)
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