# Supramolecular Bioorthogonal Nanozymes for Targeted Activation of Therapeutics

> **NIH NIH R01** · UNIVERSITY OF MASSACHUSETTS AMHERST · 2020 · $349,600

## Abstract

Project Summary/Abstract
Supramolecular Bioorthogonal Nanozymes for Targeted Activation of
Therapeutics
 In our proposed research we will create "nanozymes"—nanoparticles featuring
protein-like size and surface properties that catalyze bioorthogonal processes using
transition metal centers. These nanozymes will be used to activate prodrugs at tumor
sites, using the bioorthogonal capabilities of the nanozyme to target tumors, generating
therapeutics at the targeted tissue. We will assess these particles using in vitro models
to determine intracellular therapeutic/imaging efficacy, targeting efficiency, and hemolytic
properties. The particles will then be tested in vivo, assessing their efficacy in both
imaging and therapeutic contexts. In our proposed studies, we will
Aim 1: Fabricate nanozymes featuring different monolayer designs for optimizing
particle loading and catalyst stability. We will quantify catalytic efficiency of these
nanozymes for activating prodrugs, and determine their stability.
Aim 2: Test the intracellular activity of nanozymes in cells through activation of pro-
fluorophores and prodrugs. We will attach Her-2 targeting elements to the
nanozymes and EGFR-targeting peptides to the polymeric prodrug delivery particles,
and determine the ability to use dual "AND" targeting of nanozyme and carrier to
target only cells that overexpress both receptors.
Aim 3: Use targeted nanozymes to activate profluorophores and prodrugs at tumor
sites using orthotopic breast carcinoma models.
Aim 4: Differently targeted nanozymes and PEG/PLGA nanoparticles carrying prodrug
will be used to provide therapeutic efficacy only at tumors overexpressing both targeted
receptors, providing highly specific AND gate targeting.
The goal of this research is to create therapeutic systems capable of high specificity
through bioorthogonal chemistry. This research will build upon the supramolecular and
nanomaterials strength of Rotello coupled with the cancer biology and animal model
strengths of D. Joseph Jerry (UMass Vet. and Ani. Sci).

## Key facts

- **NIH application ID:** 9858328
- **Project number:** 5R01EB022641-04
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST
- **Principal Investigator:** VINCENT M. ROTELLO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $349,600
- **Award type:** 5
- **Project period:** 2017-05-01 → 2021-05-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858328

## Citation

> US National Institutes of Health, RePORTER application 9858328, Supramolecular Bioorthogonal Nanozymes for Targeted Activation of Therapeutics (5R01EB022641-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9858328. Licensed CC0.

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