DataVXACS NanoPaper
journal article·2022-07-26Open access

Bioorthogonal Catalysis for Treatment of Solid Tumors Using Thermostable, Self-Assembling, Single Enzyme Nanoparticles and Natural Product Conversion with Indole-3-acetic Acid

Samira Sadeghi, Nihar D. Masurkar, Girish Vallerinteavide Mavelli, Siddharth Deshpande, Warren Kok Yong Tan, Sherman Yee, Shin-Ae Kang, Yoon-Pin Lim, Edward Kai-Hua Chow, Chester L. Drum

ACS Nano· Volume 16· Issue 7
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Source abstract

Abstract

Bioorthogonal catalysis (BC) generates chemical reactions not present in normal physiology for the purpose of disease treatment. Because BC catalytically produces the desired therapy only at the site of disease, it holds the promise of site-specific treatment with little or no systemic exposure or side effects. Transition metals are typically used as catalytic centers in BC; however, solubility and substrate specificity typically necessitate a coordinating enzyme and/or stabilizing superstructure for in vivo application. We report the use of self-assembling, porous exoshells (tESs) to encapsulate and deliver an iron-containing reaction center for the treatment of breast cancer. The catalytic center is paired with indole-3-acetic acid (IAA), a natural product found in edible plants, which undergoes oxidative decarboxylation, via reduction of iron(III) to iron(II), to produce free radicals and bioactive metabolites. The tES encapsulation is critical for endocytic uptake of BC reaction centers and, when followed by administration of IAA, results in apoptosis of MDA-MB-231 triple negative cancer cells and complete regression of in vivo orthotopic xenograft tumors (p < 0.001, n = 8 per group). When Renilla luciferase (rLuc) is substituted for horseradish peroxidase (HRP), whole animal luminometry can be used to monitor in vivo activity.
Source: openalex_inverted_index · Quality: baseline

Research context

NanomaterialsBiomaterialsCatalysis & surfaces

OpenAlex topics: Click Chemistry and Applications · Nanoplatforms for cancer theranostics · Cancer Research and Treatments

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Cardiovascular Research Institute, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 9, NUHCS, Singapore 119228, Singapore

Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore

Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore 138672, Singapore

NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117456, Singapore

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore 117596, Singapore

Cancer Science Institute of Singapore, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore

Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore

Funding

Agency for Science, Technology and Research · National Medical Research Council

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