Project No. | LZP-2021/1-0593 |
|---|---|
Project coordinator
| Latvian Institute of Organic Synthesis (LIOS) |
Project leader | Dr. Antons Sizovs (LIOS) |
Implementation period | 36 months (2022-2024) |
Total cost
| 299 999,70 EUR |
Breast cancer is the most common cancer for women accounting for about 25 percent of all cancer cases for women. The aim of this project is to create a Bottle-neck Brush Polymer that will selectively accumulate in primary tumour and its metastases to serve as a nanotheranostic platform for metastatic cancer research, therapies, and diagnostics.
During implementation of the project, we will try to develop nanoparticles that effectively oppose non-specific protein absorption (opsonization) and to answer a fundamental question about the effects of nanoparticle size on pharmacokinetics, biodistribution, and its ability to accumulate in tumors.
We will develop a method for the synthesis of polymers with high polyethylene glycol content. Using fluorescence correlation spectroscopy, we will study the behaviour of these polymers in serum to demonstrate the ability to resist opsonization. In addition, we will develop a method for determining the concentration of multiple polymers in a single blood sample at the same time. Using the developed method, we will study pharmacokinetics of polymers of different sizes, their biodistribution and ability to accumulate in tumours.
Accomplished over the period 01.01.2022 - 31.12.2022
Over the course of 2022, we carried out the following research endeavors:
- Optimized the synthesis and purification of Bottle-neck Brush Polymer (BBP).
- Successfully executed multigram-scale synthesis of BBPs to yield nanoparticle surrogates with hydrodynamic diameters of 10-40 nm.
- Established an SOP for BBPs, labeling them with fluorescent dyes and subsequent purification.
- Completed pharmacokinetic (PK) and biodistribution (BD) studies of selected BBPs in a healthy cohort.
- Established methods for the extraction and quantification of BBPs in biological matrices.
- Initiated PK and BD investigations using the 4T1 Triple-Negative Breast Cancer (TNBC) model.
In 2023, we plan to continue with the implementation of the proposal, with the following objectives:
- Complete PK and BD studies of single-size BBPs in the 4T1 TNBC model.
- Complete PK and BD studies of single-size BBPs in the MDA-MB-231 TNBC model.
Publication date 03.01.2023