Enzyme-targeted nanoparticles for delivery to ischemic skeletal muscle

Literature Information

Publication Date 2017-05-24
DOI 10.1039/C7PY00568G
Impact Factor 5.582
Authors

J. L. Ungerleider, J. K. Kammeyer, R. L. Braden, K. L. Christman, N. C. Gianneschi


View Original

Abstract

The targeted delivery of enzyme-responsive nanoparticles to specific tissues can be a valuable, minimally invasive approach for imaging or drug delivery applications. In this study, we show for the first time enzyme-directed assembly of intravenously (IV) delivered nanoparticles in ischemic skeletal muscle, which has applications for drug delivery to damaged muscle of the type prevalent in peripheral artery disease (PAD). Specifically, micellar nanoparticles are cleavable by matrix metalloproteinases (MMPs), causing them to undergo a morphological switch and thus aggregate in tissues where these enzymes are upregulated, like ischemic muscle. Here, we demonstrated noninvasive in vivo imaging of these IV-injected nanoparticles through near-infrared dye labeling and in vivo imaging (IVIS) particle tracking in a rat hindlimb ischemia model. Polymer peptide amphiphilic nanoparticles were synthesized and optimized for both MMP cleavage efficiency and near-IR fluorescence. Nanoparticles were injected 4 days after unilateral hindlimb ischemia and were monitored over 28 days using IVIS imaging. Nanoparticles targeted to ischemic muscle over healthy muscle, and ex vivo biodistribution analysis at 7 and 28 days post-injection confirmed targeting to the ischemic muscle as well as off target accumulation in the liver and spleen. Ex vivo histology confirmed particle localization in ischemic but not healthy muscle. Altering the surface charge of the nanoparticles through addition of zwitterionic dye species resulted in improved targeting to the ischemic muscle. To our knowledge, this is the first study to demonstrate the targeted delivery and long term retention of nanoparticles using an enzyme-directed morphology switch. This has implications for noninvasive drug delivery vehicles for treating ischemic muscle, as no minimally invasive, non-surgical options currently exist.

Related Literature

Recent advances in transition metal-catalyzed olefinic C–H functionalization

Bingxian Liu, Lingyun Yang, Pengfei Li, Fen Wang

2020-12-23 Review Article

DOI: 10.1039/D0QO01159B

New perspective of electron transfer chemistry

2003-01-30 Perspective

DOI: 10.1039/B300053B

Inside front cover

2021-03-23 Cover

DOI: 10.1039/D1QO90024B

Metal-ion-assisted hydrolysis of dipeptides involving a serine residue in a neutral aqueous solution

Morio Yashiro, Yoko Sonobe, Ai Yamamura, Tohru Takarada, Makoto Komiyama, Yuki Fujii

2003-01-23 Paper

DOI: 10.1039/B209565C

Theoretical study of rhodium- and cobalt-catalyzed decarboxylative transformations of isoxazolones: origin of product selectivity

Wei Rong, Tian Zhang, Ting Li, Juan Li

2021-01-26 Research Article

DOI: 10.1039/D0QO01498B

Trimeric and dimeric sesquiterpenoids from Artemisia atrovirens and their cytotoxicities

Tian-Ze Li, Chang-An Geng, Yun-Bao Ma, Xiao-Yan Huang, Jin-Ping Wang, Xue-Mei Zhang

2021-01-22 Research Article

DOI: 10.1039/D0QO01615B

Nitriles as radical acceptors in radical cascade reactions

Kai Sun, Ying-Wu Lin, Bing Yu

2020-10-26 Review Article

DOI: 10.1039/D0QO01058H

Back cover

2021-03-09 Cover

DOI: 10.1039/D1QO90021H

Carbon dioxide-promoted palladium-catalyzed dehydration of primary allylic alcohols: access to substituted 1,3-dienes

Yan-Kai Huang, Wen-Zhen Zhang, Ke Zhang, Wen-Le Wang, Xiao-Bing Lu

2020-12-30 Research Article

DOI: 10.1039/D0QO01465F

You might also like

Compound Q&A

What is Ethyl 3-cyclohexylpropanoate (CAS: 10094-36-7)?

Ethyl 3-cyclohexylpropanoate is a clear, colorless to light yellow liquid with a...

10094-36-7Ethyl 3-cyclohexylpr...
Compound Q&A

How should waste containing 2-(Hydroxymethyl)-5-(methoxycarbonyl)-6-methyl-4-(2-nitrophenyl)nicotinic acid (CAS: 34783-31-8) be handled?

Waste containing 2-(Hydroxymethyl)-5-(methoxycarbonyl)-6-methyl-4-(2-nitrophenyl...

34783-31-82-(Hydroxymethyl)-5-...
Compound Q&A

How should waste containing 2,4,6-Tris(pentafluoroethyl)-1,3,5-triazine (CAS: 858-46-8) be handled?

Waste containing 2,4,6-Tris(pentafluoroethyl)-1,3,5-triazine (CAS: 858-46-8) sho...

858-46-82,4,6-Tris(pentafluo...
Compound Q&A

What precautions should be taken when handling Chloroac-nle-oh (CAS: 56787-36-1)?

When handling Chloroac-nle-oh (CAS: 56787-36-1), it is essential to wear appropr...

56787-36-1Chloroac-nle-oh
Compound Q&A

What industries use Ethyl 6-phenylimidazo[2,1-b][1,3]thiazole-3-carboxylate (CAS: 752244-05-6)?

Ethyl 6-phenylimidazo[2,1-b][1,3]thiazole-3-carboxylate is primarily used in the...

752244-05-6Ethyl 6-phenylimidaz...
Compound Q&A

Are there alternatives to alpha-(2-Bromophenyl)benzylamine (CAS: 55095-15-3) in synthesis?

Alternatives to alpha-(2-Bromophenyl)benzylamine (CAS: 55095-15-3) in synthesis ...

55095-15-3alpha-(2-Bromophenyl...
Compound Q&A

How should waste containing 2-Chloro-5-methoxypyridine (CAS: 139585-48-1) be handled?

Waste containing 2-Chloro-5-methoxypyridine (CAS: 139585-48-1) should be managed...

139585-48-12-Chloro-5-methoxypy...
Compound Q&A

What industries use 1-(4-Methoxyphenyl)-2,5-dimethyl-1H-pyrrole (CAS: 5044-27-9)?

1-(4-Methoxyphenyl)-2,5-dimethyl-1H-pyrrole (CAS: 5044-27-9) is used in various ...

5044-27-91-(4-Methoxyphenyl)-...
Compound Q&A

Are there alternatives to 3-Bromo-5-(N-Boc)aminomethylisoxazole (CAS: 903131-45-3) in synthesis?

There are alternative reagents and compounds that can be used in the synthesis o...

903131-45-33-Bromo-5-(N-Boc)ami...
Compound Q&A

What is Tungsten(IV) oxide (CAS: 12036-22-5)?

Tungsten(IV) oxide, also known as tungsten dioxide, is a chemical compound with ...

12036-22-5Tungsten(IV) oxide

Source Journal

Polymer Chemistry

Polymer Chemistry
CiteScore: 8.6
Self-citation Rate: 7.3%
Articles per Year: 457

Polymer Chemistry welcomes submissions in all areas of polymer science that have a strong focus on macromolecular chemistry. Manuscripts may cover a broad range of fields, yet no direct application focus is required.

Recommended Compounds

Recommended Suppliers

Disclaimer
This page provides academic journal information for reference and research purposes only. We are not affiliated with any journal publishers and do not handle publication submissions. For publication-related inquiries, please contact the respective journal publishers directly.
If you notice any inaccuracies in the information displayed, please contact us at support@chemtradehub.com. We will promptly review and address your concerns.