# Subcellular enzyme-instructed self-assembly for molecular anticancer nanomedicines

> **NIH NIH R01** · BRANDEIS UNIVERSITY · 2022 · $389,109

## Abstract

ABSTRACT
 Despite the progress in molecular therapy and immunotherapy, multiple underlying cellular mechanisms
cause resistance to cancer therapy. There are urgent needs to develop innovative approaches to meet these
challenges. The proposed study is to develop subcellular enzyme-instructed self-assembly (sEISA), which
includes mitochondrial EISA (mitoEISA) and cytoplasmic EISA (cytoEISA), for generating molecular nanofibers
to overcome drug resistance and immunosuppression in cancer therapy. Our preliminary studies have shown
that sEISA selectively targets the mitochondria of cancer cells and minimizes drug resistance. Most importantly,
our preliminary study shows that sEISA inhibits the growth of immunosuppressive tumors in vivo. Thus, we
propose to further develop sEISA against drug resistant cancer cells and tumors. The proposed research has
three specific aims: Aim 1, developing mitoEISA for selectively targeting cancer cells; Aim 2, developing
cytoEISA for minimizing drug resistance and immunosuppression; and Aim 3, evaluating sEISA in ovarian
cancer xenograft murine models. The central hypothesis is that sEISA spatiotemporally generates molecular
nanofibers, which interact with multiple cellular proteins and interrupt multiple cellular processes inside cancer
cells to minimize drug resistance. Our preliminary results support the central hypothesis. The innovation is that
the mechanisms of the action of the molecular nanofibers significantly depart from the ligand-receptor dogma of
the current anticancer drugs. The long-term goal of the proposed work is to develop sEISA to generate molecular
nanofibers for overcoming resistance in cancer therapy. We anticipate that this research will provide innovative
anticancer approaches to address the problems of drug resistance and immunosuppression in cancer therapy,
thus ultimately will improve the survivorship of cancer patients.

## Key facts

- **NIH application ID:** 10368990
- **Project number:** 5R01CA142746-12
- **Recipient organization:** BRANDEIS UNIVERSITY
- **Principal Investigator:** Bing Xu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $389,109
- **Award type:** 5
- **Project period:** 2010-02-08 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10368990

## Citation

> US National Institutes of Health, RePORTER application 10368990, Subcellular enzyme-instructed self-assembly for molecular anticancer nanomedicines (5R01CA142746-12). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10368990. Licensed CC0.

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