# Active Delivery of Platinum Nanoimmunoconjugates to Improve Breast Cancer Therapy

> **NIH NIH R01** · PROTEOGENOMICS RESEARCH INSTIT/SYS/ MED · 2020 · $464,041

## Abstract

The overall objective of the proposed research is to utilize a newly discovered, active transendothelial transport
pathway, the caveolae pumping system, in order to provide an effective solution to the delivery and toxicity
problem of Pt(II)-based chemotherapeutics in breast cancer. Systemic chemotherapy is one of the common
forms of breast cancer treatments, however clinical efficacy of Pt(II) antitumor drugs is limited by the significant
in vivo barriers inhibit delivery of these drugs into solid tumors, requiring the use of high doses, producing
serious side effects and facilitating development of drug resistance. In order to address these problems and
significantly improve treatment of breast cancer we propose two novel paradigms: 1) our newly discovered
endothelial cell (EC) caveolae targeting system to sidestep passive delivery and dramatically enhance speed
and efficiency of tumor penetration, and 2) to design and develop novel platinum(II) supramolecular
coordination complexes (Pt(II)-SCCs), the nanoparticles (NPs) that have shown remarkable efficacy in tumor
destruction in preclinical breast cancer models while being monodisperse, stable and well-characterized. Our
main hypothesis is that immunoconjugates that fully utilize the advantages of caveolae-targeting antibodies will
increase Pt(II)-SCCs delivery into tumors for enhanced efficacy and reduced toxicity, potentially resulting in a
fundamentally new class of anticancer therapeutics. This hypothesis will be tested by the following specific
aims: In Aim 1, we plan to design and synthesize Pt(II)-SCC immunoconjugates. In this Aim will also design,
synthesize and characterize the chemical identity, purity and physicochemical properties of our Pt(II)-SCCs
immunoconjugates. We will use caveolae-targeted antibody which we have shown can move the attached
cargo from the blood across the EC barrier into solid tumor with unprecedented speed and specificity. In Aim 2
we will characterize in vivo delivery of Pt(II)-SCC immunoconjugates targeting the EC caveolae in tumors. We
will perform dynamic monitoring of antibody-Pt(II)-SCC targeting in real time in live mice with intravital
microscopy (IVM) using fluorescence emission of the assembled SCCs. In Aim 3 we will assess the
therapeutic efficacy of the EC-targeting Pt(II)-SCC immunoconjugates. The efficacy of our targeted delivery
system will be examined in IVM models using fluorescence microscopy and in non-IVM Her2/Neu tumor
models with whole-body animal imaging. The long-term goal of this project is to translate our key basic
discoveries into an innovative drug delivery platform in order to improve therapeutic efficacy and reduce toxicity
in the breast cancer treatment.

## Key facts

- **NIH application ID:** 9893830
- **Project number:** 5R01CA215157-04
- **Recipient organization:** PROTEOGENOMICS RESEARCH INSTIT/SYS/ MED
- **Principal Investigator:** Bogdan Olenyuk
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $464,041
- **Award type:** 5
- **Project period:** 2017-03-10 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893830

## Citation

> US National Institutes of Health, RePORTER application 9893830, Active Delivery of Platinum Nanoimmunoconjugates to Improve Breast Cancer Therapy (5R01CA215157-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9893830. Licensed CC0.

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