# Biodegradable nanocarriers and antibodies as targeting delivery vehicles for cancer metallodrugs

> **NIH NIH SC1** · BROOKLYN COLLEGE · 2020 · $392,500

## Abstract

PROJECT SUMMARY
Several metal-based compounds highly effective in cancers resistant to cisplatin and other
chemotherapeutic agents but with fewer side effects, have been described over the past decade
including some examples from our group at Brooklyn College. Despite the efficacy in patients or in
pre-clinical models of these novel inorganic compounds and FDA approved platinum derivatives,
there are some difficulties in most cases, related to pharmaceutical deficiencies such as poor water
solubility, low bioavailability and short circulating time. Thus, there is a need to improve the delivery of
these drugs so that they can be efficiently released at the specific tumor site without affecting healthy
tissues. The ultimate goal of this proposal is to develop safe and highly selective metal-based
anticancer chemotherapeutics by either incorporation into biodegradable enzyme-specific cleavable
nanocarriers or by conjugation to specific monoclonal antibodies. The specific aims of this proposal
are the following: Aim 1. Determine the selectivity and efficacy of “smart” biodegradable nanocarriers
that can release metallodrugs by specific enzyme cleavage. We hypothesize that by exploiting local
enzyme overexpression in certain cancer types, we can use biodegradable peptide-based carriers that
are prone to self-assembly and form localized fiber-based depots. To do this, we will prepare and
encapsulate selected organometallic compounds with relevant antitumor properties in vitro and in
vivo, into novel MMP-9-cleavable peptide-amphiphiles. We will then evaluate the anticancer
properties of the resulting nanocarrier-metallodrug conjugates (NMDCs) in vitro and in vivo in cells
and tumors which overexpress MMP-9, an enzyme associated with cancer progression, cancer
invasion and metastasis. We will focus on specific breast and renal cancers.
Aim 2. Determine the selectivity and efficacy of monoclonal antibodies as targeting vehicles to deliver
metal-based cytotoxic payload to tumor cells. We hypothesize that that the incorporation of a highly
cytotoxic metallodrug to monoclonal antibodies will selectively deliver it to the specific tumor. To
generate stable antibody drug conjugates (ADCs), we will synthesize synthons containing highly
cytotoxic gold(I)-fragments based on phosphane and mainly N-heterocyclic carbene ligands and
appropriate linkers amenable for bioconjugation to the monoclonal antibody trastuzumab. We will
evaluate the in vitro and in vivo anti-tumor activity of selected gold-based ADC in cancers that
overexpress HER2/neu. Trastuzumab is known to interfere with HER2/neu (ERBB2) receptors
overexpressed in certain cancers. More specifically, we will be evaluating specific ovarian, breast,
colon and gastric cancer cell lines and xenografts.

## Key facts

- **NIH application ID:** 9934216
- **Project number:** 5SC1GM127278-07
- **Recipient organization:** BROOKLYN COLLEGE
- **Principal Investigator:** Maria Contel
- **Activity code:** SC1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $392,500
- **Award type:** 5
- **Project period:** 2018-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934216

## Citation

> US National Institutes of Health, RePORTER application 9934216, Biodegradable nanocarriers and antibodies as targeting delivery vehicles for cancer metallodrugs (5SC1GM127278-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9934216. Licensed CC0.

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