# ROS-responsive Chemical Modification of Protein and Its Delivery

> **NIH NIH R01** · TUFTS UNIVERSITY MEDFORD · 2022 · $348,007

## Abstract

PROJECT SUMMARY
Intracellular protein therapies are tremendously appealing, promising treatments for many heretofore untreatable
diseases, including genetic diseases and cancers. However, the safe, efficient intracellular delivery of proteins
remains a challenge. Here we propose the development of an effective cytoplasmic delivery strategy for
therapeutic proteins for cancer treatment: A combination of reversible chemical modification of proteins and
nanocomplexation with cationic lipid-based nanoparticles. The chemical modification will inactivate the cytotoxic
proteins, making them effectively nontoxic to normal cells. However, upon encountering increased level of
reactive oxygen species (ROS), i.e. inside the cancer cells, the modified chemical moiety will be cleaved and the
biological function of the proteins will be restored, resulting in cytotoxic action. Simultaneously, chemical
modification reduces the surface charge of proteins, leading to more efficient nanocomplexation and delivery by
bioreducible cationic lipid-like molecules. This protein delivery platform may thus serve as an efficient tumor-
specific targeting system for cancer treatment.
To accomplish the objective of this application, we propose the following three Specific Aims:
Specific Aim 1: ROS-responsive modification of saporin and its characterization. To develop an approach
for chemical modification of saporin, characterize the modification, and investigate the cleavage of the modified
moieties at elevated ROS levels.
Specific Aim 2: Intracellular delivery of saporin-NBC using synthetic lipids. To study a new class of
synthetic lipid-based nanoparticles for intracellular saporin-NBC delivery in both cancerous and non-cancerous
cells, and to study the synergistic effect of intracellular delivery of saporin-NBC and ROS-inducing anticancer
drugs in suppressing triple-negative breast cancer cells.
Specific Aim 3: Studying the in vivo saporin-NBC delivery in mouse breast cancer model.
To study the therapeutic efficacy of bioreducible lipids in delivering proteins to inhibit tumor growth in murine
breast cancer mouse models.

## Key facts

- **NIH application ID:** 10213723
- **Project number:** 5R01EB027170-04
- **Recipient organization:** TUFTS UNIVERSITY MEDFORD
- **Principal Investigator:** Qiaobing Xu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $348,007
- **Award type:** 5
- **Project period:** 2018-09-18 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10213723

## Citation

> US National Institutes of Health, RePORTER application 10213723, ROS-responsive Chemical Modification of Protein and Its Delivery (5R01EB027170-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10213723. Licensed CC0.

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