Polymersomes efficiently deliver siRNA to treat breast cancers in preclinical model

The promise of small interfering RNAs is that they can specifically knock down oncogenes that promote tumor growth without the toxicity that accompanies chemotherapy. The delivery vehicle that protects the siRNAs from degradation and clearance on their journey through the bloodstream to the cancer tumor is needed.

The University of Alabama at Birmingham has demonstrated a 100 nanometer polymersome that can carry PARP1 siRNA to triple-negative breast cancer tumors in mice. Breast cancer-bearing mice were four times more likely to survive after the siRNA knocked down the expression of the PARP1 genes.

PARP inhibitors have been successful in targeting tumors with defects in DNA repair. Due to bone marrow suppression, it has been difficult to combine many of the PARP inhibitors. Combining treatments that target PARP1 in the tumor may be possible.

To the best of our knowledge, our work is the first example of non-ionic polymeric nanoparticles that are capable of efficiently encapsulating and delivering PARP1 siRNA to knock down PARP1 in the body.

The approach for the delivery of the PARP1 siRNA to breast cancer cells uses three block copolymers linked together in a straight chain. The first block has a 14-molecule chain of N-vinylrolidone, the second block has a 47-molecule chain of dimethylsiloxane, and the third block has a 14-molecule chain of N-vinylrolidone.

The researchers at the University of Alabama at Tuscaloosa used simple methods to assemble the block polymers into a robust shell thickness of 13 nanometers. Consistency of quality control is possible with the assembly method.

In the presence of a single micromolar PARP1 siRNA, the Polymersomes were able to load the RNA inside the nanocarriers. The siRNA was not released when these were broken open. 18 hours after the injection of the dye-laden nanocarriers into the tumors, the dye had accumulated in the tumors through passive targeting.

The team tested the siRNA-laden polymersomes with HER2 positive breast cancer cells. The researchers had previously reported that they had reduced the levels of the PARP1 in the cells.

Researchers suggest that targeting molecule can be added the same way as the fluorescent dye to make thecapsule home in to a tumor.

The ability of these non-ionic, biodegradable PVPON 14 to successfully knock down PARP1 in the body has a strong potential to become.

Poly(N-vinylpyrrolidone) and poly(dimethylsiloxane) are the two main colors of the product. The siRNAs that the polymersomes can carry are small, about 21 to 25 nucleotides long, and can be used to specifically suppress oncogene expression.

More information: Yiming Yang et al, Poly(N-vinylpyrrolidone)-block-Poly(dimethylsiloxane)-block-Poly(N-vinylpyrrolidone) Triblock Copolymer Polymersomes for Delivery of PARP1 siRNA to Breast Cancers, ACS Applied Bio Materials (2022). DOI: 10.1021/acsabm.2c00063 Citation: Polymersomes efficiently deliver siRNA to treat breast cancers in preclinical model (2022, May 24) retrieved 25 May 2022 from https://phys.org/news/2022-05-polymersomes-efficiently-sirna-breast-cancers.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.