Small interfering RNAs (siRNAs) are commonly used in molecular biology for silencing a targeted gene. They are artificially synthesized 19-23 nucleotide long-stranded RNA molecules that hold promise to treat tumors. However, they still need a delivery vehicle that will protect them from degradation throughout their journey in the bloodstream to cancer cells.
Researchers from the University of Alabama at Birmingham recently demonstrated a 100-nanometer polymersome that safely and efficiently delivers siRNA to triple-negative breast cancer tumors in mice. There, siRNA could knock down the expression of the DNA repair enzyme PARP1 and increase the survival chances of the mice by four times.
Polymersomes for Therapeutic Delivery of siRNA
Usually, the cancer drug PARP inhibitors successfully target tumors with defects in DNA. But bone marrow suppression has made it challenging for PARP inhibitors to combine with chemotherapy.
In the new study titled "Polymersomes for Therapeutic Delivery of Protein and Nucleic Acid Macromolecules: From Design to Therapeutic Applications," published in ACS Applied Bio Materials, researchers shared the first example of biodegradable, non-ionic polymeric nanovesicles that can efficiently encapsulate and deliver PARP1 siRNA to targeted cancer tumors.
According to Phys.org, the fast and safe approach of using polymersomes to deliver PARP1 siRNA to breast cancer cells could help develop effective drug delivery to treat the illness.
It uses three biodegradable block copolymers linked in a straight chain. The first block is a chain of 14 molecules of N-vinylpyrrolidone connected to the second chain of 47 molecules of dimethylsiloxane and linked to the third block of 14 molecules of N-vinylpyrrolidone.
It created a robust 100 nanometer-diameter, hollow-sphere polymersomes with a thickness of about 13 nanometers. The team noted that the method they used to assemble it can create a large-scale production with consistent quality.
The polymersomes were able to load the RNA inside the nanocarriers, so when they are broken using ultrasound after reaching their target, the siRNA is released unchanged. They also tested the siRNA-loaded polymersomes with HER2-positive, trastuzumab-resistant breast cancer cells. They found that it inhibited the proliferation of PARP1 in the cells and suppressed the NF-κB transcription factor pathway, just like previous studies.
Polymersomes in Nanomedicine
Nanomedicine has gained attention in the past years as it continues to lead the development of new approaches for medical treatments, specifically in targeting cancer. One of these methods is using polymersomes as vehicles for different medical applications.
The news release reported that researchers of the new study believe that the polymersomes are capable of efficiently delivering siRNA to knockdown PARPP1 in vivo and have a strong potential of becoming an advanced platform for developing precision-targeted therapeutic carriers. In that way, researchers in the future could develop highly effective drug delivery nanocarriers for breast cancer tumors.
They noted that polymersomes are so small that they are only about 21 to 25 nucleotides long and can specifically inhibit oncogene expression.
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