# TOWARD TRANSLATION OF NANFORMULATED PACLITAXEL-PLATINUM COMBINATION

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $600,798

## Abstract

TOWARD TRANSLATION OF NANFORMULATED PACLITAXEL-PLATINUM COMBINATION
The goal of this proposal is to obtain pre-clinical data to enable the translation of a novel nanotechnology-based
drug combination to treat triple negative breast cancer (TNBC). TNBC accounts for ∼10-20% of breast cancers
and is associated with relatively poor prognosis, earlier disease recurrence and higher number of visceral
metastases. Chemotherapy, in particular with anthracyclines and taxanes, remains the backbone medical
management for both early and metastatic TNBC but a significant proportion of patients with early-stage TNBC
unfortunately develop metastatic disease. Combination treatments using platinates and taxanes were shown to
increase pathologic complete response rates in TNBC and improve survival in neoadjuvant treatment settings.
We propose to use nanotechnology to improve the treatment of TNBC by co-delivering platinum and taxane
drugs in the same nanoparticle to attack cancer cells in a synergistic fashion and produce greater antitumor
effect. To address poor miscibility and drug loading of platinates and taxanes in many nanoparticles, we propose
to use a high capacity polymeric micelles (PMs) of poly(2-oxazolne) (POx) block copolymers to incorporate
drugs. In preliminary work we developed POXOL-CP PMs, a combination of PTX and hydrophobic cisplatin
prodrug co-loaded in POx block copolymer micelles that has shown pharmacological synergy of solubilized
drugs, better delivery of both drugs to tumors and improved efficacy in several animal models compared to the
small molecule agents or their combination administered separately. The goal of this proposal is to obtain
additional pre-GLP data for our new combination nanotherapeutic in rodent and non-human primate (NHP)
models, develop validated assays and procedures for POXOL-CP PMs, further demonstrate its safety and
efficacy and establish path for translation of POXOL-CP PMs to the clinic for TNBC patients. The project
addresses the following aims: 1) Manufacture reproducible, stable, and safe POXOL-CP PMs, validate its safety
and improved drug delivery to tumors in a mouse model of TNBC; 2) Demonstrate activity of POXOL-CP PMs
compared to standard of care in Orthotopic Syngeneic Transplant (OST) and Genetically Engineered Mouse
Models (GEMM) of TNBC that recapitulate the human disease. 3) Assess safety and PK profiles of POXOL-CP
PMs in rat and NHP models. We will follow Good Experimental Practice (GEP) in data keeping and recording
and develop Standard Operating Procedures (SOP) and follow guidance of a clinical and translational panel. If
successful the results of this project will allow forming data package to support the Good Laboratory Practice
(GLP) and Good Manufacturing Practice (GMP) work and compete for NCI Experimental Therapeutics (NExT)
program, and/or other resources to advance development of POXOL-CP PMs on a path to the clinic to improve
treatment outcomes for patients with TNBC.

## Key facts

- **NIH application ID:** 10436355
- **Project number:** 5R01CA264488-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** ALEXANDER V KABANOV
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $600,798
- **Award type:** 5
- **Project period:** 2021-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436355

## Citation

> US National Institutes of Health, RePORTER application 10436355, TOWARD TRANSLATION OF NANFORMULATED PACLITAXEL-PLATINUM COMBINATION (5R01CA264488-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10436355. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*