# Overcoming Tumor Resistance with Enzyme-Instructed Nanoscale Assemblies and Immunotherapies

> **NIH NIH K00** · HARVARD UNIVERSITY · 2020 · $85,666

## Abstract

Project Summary/Abstract
 Resistance to chemotherapy and molecularly targeted therapies is a major problem facing
current cancer research. The development of drug resistance could lead to chemotherapy failure and
tumor relapse, resulting in reduced survival rates. In addition, despite the unprecedented success
achieved in cancer immunotherapy over the past decades, the cancer-cell-intrinsic mechanisms of
resistance result in low response rates of patients which remains a major challenge. Therefore, it is
urgently necessary to develop novel therapy to address these problems. Recently, our laboratory,
headed by my sponsor Dr. Bing Xu, developed anticancer nanomedicine based on enzyme-instructed
self-assembly (EISA). The EISA is capable of selective inhibition of tumor without harming normal
tissues due to its precise spatiotemporal control. Additionally, by targeting multiple targets, EISA hardly
induces acquired drug resistance. Most importantly, combination therapy holds great promise for tumor
prevention and treatment. The overall goal of this project is to overcome cancer drug resistance
through the application of nanotechnology and combination with anticancer immunotherapy. To achieve
this goal, we proposed two following specific aims:
 1) During the F99 phase, I propose to develop anticancer nanomedicines based on EISA to
target loss-of-function (downregulation) and endoplasmic reticulum (ER) in cancer cells for minimizing
the drug resistance and side effect. We designed a two enzyme controlled assembly system to target
the downregulation via the combination of enzyme-instructed assembly and disassembly and tested its
anticancer efficacy and selectivity. We will also study the EISA in targeting ER for cancer inhibition. The
ER targeting ability and dynamic distribution of the designed molecules will be tested. Moreover, we
will elucidate the mechanisms of cancer cell death induced by ER targeting.
 2) For the K00, the direction of my postdoctoral research will focus on improving the anti-tumor
response of immunotherapy through the combination with EISA based nanomedicines. The proposed
postdoctoral training will provide me with new insight and techniques in cancer immunology.

## Key facts

- **NIH application ID:** 10073633
- **Project number:** 4K00CA234746-03
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Zhaoqianqi Feng
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $85,666
- **Award type:** 4N
- **Project period:** 2020-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10073633

## Citation

> US National Institutes of Health, RePORTER application 10073633, Overcoming Tumor Resistance with Enzyme-Instructed Nanoscale Assemblies and Immunotherapies (4K00CA234746-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10073633. Licensed CC0.

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