Synthetic networks with tunable responsiveness, biodegradation, and molecular recognition for precision medicine applications

Formulations and devices for precision medicine applications must be tunable and multiresponsive to treat heterogeneous patient populations in a calibrated and individual manner. We engineered modular poly(acrylamide-co-methacrylic acid) copolymers, cross-linked into multiresponsive nanogels with ei...

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Bibliographic Details
Published in:Science advances 2019-09, Vol.5 (9), p.eaax7946
Main Authors: Clegg, John R, Irani, Afshan S, Ander, Eric W, Ludolph, Catherine M, Venkataraman, Abhijeet K, Zhong, Justin X, Peppas, Nicholas A
Format: Article
Language:English
Subjects:
Acrylic Resins - chemistry
Acrylic Resins - pharmacokinetics
Acrylic Resins - pharmacology
Animals
Applied Sciences and Engineering
Cell Line, Tumor
Drug Carriers - chemical synthesis
Drug Carriers - chemistry
Drug Carriers - pharmacokinetics
Drug Carriers - pharmacology
Humans
Materials Science
Methacrylates - chemistry
Methacrylates - pharmacokinetics
Methacrylates - pharmacology
Mice
Nanogels - chemistry
Nanoparticles - chemistry
Precision Medicine
RAW 264.7 Cells
SciAdv r-articles
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Summary:Formulations and devices for precision medicine applications must be tunable and multiresponsive to treat heterogeneous patient populations in a calibrated and individual manner. We engineered modular poly(acrylamide-co-methacrylic acid) copolymers, cross-linked into multiresponsive nanogels with either a nondegradable or degradable disulfide cross-linker, that were customized via orthogonal chemistries to target biomarkers of an individual patient's disease or deliver multiple therapeutic modalities. Upon modification with functional small molecules, peptides, or proteins, these nanomaterials delivered methylene blue with environmental responsiveness, transduced visible light for photothermal therapy, acted as a functional enzyme, or promoted uptake by cells. In addition to quantifying the nanogels' composition, physicochemical characteristics, and cytotoxicity, we used a QCM-D method for characterizing nanomaterial degradation and a high-throughput assay for cellular uptake. In conclusion, we generated a tunable nanogel composition for precision medicine applications and new quantitative protocols for assessing the bioactivity of similar platforms.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.aax7946