New efforts to improve the effectiveness of nucleotide-based drugs against prostate cancer and bone metastases
University of Minnesota researcher Hongbo Pang, published in Advanced Functional Materials, conducted an inter-agency study to improve the effectiveness of nucleotide-based drugs against prostate cancer and bone metastases.
In this study, Pang and his research team investigated whether liposomes, when integrated into the iRGD peptide, help concentrate antisense oligonucleotides (ASOs) in primary prostate tumors and their bone metastases. Liposomes are used as a drug delivery system, and ASOs are a type of nucleotide drug.
More importantly, they were looking to see if this system helps more drugs across the vessel wall and deep into the tumor tissue. This is critical because, while nucleotide drugs offer unique advantages in treating tumors and other diseases, they often suffer from poor efficiency in traversing blood vessels and entering tumor tissue where their targets are. This problem severely limits their clinical applicability and effectiveness.
Our system shows a good ability to deliver more ASOs to both primary tumor tissue and bone metastases – this is the primary site for prostate cancer metastasis. This further leads to a significant improvement in ASO effectiveness in order to inhibit the growth of primary tumor and bone metastases. We expect this system to become a universal delivery system to improve the clinical efficacy of ASOs and other nucleotide drugs. “
Hongbo Pang, Assistant Professor, College of Pharmacy, member of the Masonic Cancer Center
The study found that:
- iRGD liposomes may increase tumor accumulation and vascular / tissue penetration by ASOs against the disease-causing gene of prostate cancer;
- The ability of ASOs to inhibit the growth of both primary tumors and bone metastases was significantly improved by iRGD liposomes.
- and a long-term tumor inhibition study was also performed which showed that iRGD liposomes significantly prolong AR-ASO suppression of primary tumor growth.
Pang and his team say iRGD liposomes have proven to be a desirable delivery system for ASOs and hold promise to improve the clinical efficacy of nucleotide drugs in cancer therapies.
Guan, J. et al. (2021) iRGD liposomes improve tumor delivery and therapeutic efficacy of antisense oligonucleotide drugs against primary prostate cancer and bone metastases. Extended functional materials. doi.org/10.1002/adfm.202100478.