# A multiplexed approach to improve tumoral targeting and chemotherapeutic treatment

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $467,521

## Abstract

Project Summary/Abstract
 Triple-negative breast cancer (TNBC) accounts for 15-20% of breast cancer cases. The lack of targeted
therapies and poor prognosis have resulted in a major effort to discover molecular targets to improve outcomes.
While there is increasing understanding of the molecular heterogeneity of tumors, clinical trials of targeted agents
have thus far been disappointing. Chemotherapeutic agents such as anthracycline and taxanes remain the
backbone of medical management for both early and metastatic TNBC. This approach is toxic to normal in
addition to tumor cells, leading to treatment burden and undesired side effects. These drugs are given to the
patients in hope of the benefits to outweigh the risks. One significant approach to improve outcomes is the
development of nanocarriers to achieve targeted delivery to tumors and reducing toxicity. To date, antitumor
activities of the current FDA-approved nanomedicines (Doxil and Abraxane) have been moderate compared to
the free drugs. There is an unmet need for an approach that can overcome different physiological barriers to
deliver higher concentration of drugs in a more specific manner. Our long-term goal is to develop a platform to
improve chemotherapeutics for achieving safer and more effective treatments. The objective is to develop a
platform to overcome multiple barriers in tumor-specific delivery. We propose a biocompatible, non-
immunogenic, self-assembling peptide-based nanofiber precursor (NFP). The factors that are essential in
effective therapies are (a) co-delivering an optimal drug ratio of a combination therapy, (b) shape-controlled
promotion of drug uptake, (c) charge-assisted tumor penetration, (d) enzyme-induced tumor retention (ETR),
and (e) pH-activated controlled drug release approaches to be utilized by NFP. High PEG content of NFP
minimizes its capture by the RES. Our overarching hypothesis is that such a multiplexed platform will significantly
improve therapeutic efficacy and safety when used as a drug carrier. Our preliminary data have shown that NFP
incorporated with doxorubicin has a superior therapeutic efficacy with minimal host toxicity compared to the free
drug and Doxil. Our rationale is to maximize the delivery of NFP to the tumor, which requires us understand the
contribution of NFP’s physicochemical properties (such as size and surface charges, ETR kinetics, and drug
release profiles) in their biodistribution and uptake, penetration, and retention. Our specific aims will focus on the
(Aim1) Refinement of different physicochemical properties, including size, shape, charge, and functional
domains, affecting the in vivo behavior of NFP; and (Aim 2) Evaluation of the therapeutic efficacy of controlled-
release NFP as a carrier of chemotherapy. This information will be critical for optimal formulation of multi-drug
combinations in the most effective drug ratio to significantly improve the treatment outcomes. While we will utilize
TNBC to develop the opti...

## Key facts

- **NIH application ID:** 9948596
- **Project number:** 5R01CA222802-03
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Benedict Shek Hang Law
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $467,521
- **Award type:** 5
- **Project period:** 2018-07-03 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948596

## Citation

> US National Institutes of Health, RePORTER application 9948596, A multiplexed approach to improve tumoral targeting and chemotherapeutic treatment (5R01CA222802-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9948596. Licensed CC0.

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