Enhancing Cancer Gene Therapy with Nanoparticle-Based Delivery Systems
Researchers from Mashhad University of Medical Sciences have published a new study in the journal Drug Delivery, detailing the development of a novel strategy for enhancing the delivery of cancer gene therapy using nanoparticle-based delivery systems. The study focuses on the use of minoxidil-loaded nanoliposomes (Lip-MXD) to induce tumor vasodilation and improve the penetration of PEGylated liposomal doxorubicin (PLD) into solid tumors. The research team employed a remote loading method to encapsulate minoxidil into liposomes, achieving high encapsulation efficiency and multifunctional effects.
Key Takeaways:
- The researchers developed a novel strategy using minoxidil-loaded nanoliposomes (Lip-MXD) to induce tumor vasodilation and enhance the delivery of PEGylated liposomal doxorubicin (PLD).
- The remote loading method achieved high minoxidil encapsulation efficiency (87%) and an average particle size of 111 nm.
- Pretreatment with Lip-MXD demonstrated multifunctional effects, including downregulation of CLDN-1 expression, improvement of NP penetration into advanced tumors, and stabilization of the interaction between CLDN-1 and MXD by molecular dynamics simulation.
- Immunohistochemistry and gene expression analyses in mouse models of colorectal and pancreatic cancers revealed that Lip-MXD administration significantly reduced the number of tumor-associated stromal cells.
- Lip-MXD administration mitigated tumor hypoxia and substantially enhanced PLD permeability within the dense microenvironment of desmoplastic tumors through its vasodilatory effects.
- A single dose of PLD following Lip-MXD pretreatment exhibited significant antitumor activity, resulting in a prolonged survival rate of 60% in the Lip-MXD+PLD-treated group in CRC models.
- The study suggests that this MXD liposomal formulation presents a promising method to overcome tumor penetration, enhance NP delivery, and improve therapeutic outcomes in CRC and PCa cancers.
Statistics:
- High minoxidil encapsulation efficiency: 87%
- Average particle size of Lip-MXD: 111 nm
- Prolonged survival rate in CRC models: 60%
- Significant reduction in tumor volume in PCa models: 14-day evaluation period
Sources:
- NewsRx. Researchers from Mashhad University of Medical Sciences Describe Findings in Cancer Gene Therapy (Enhancing targeted delivery and efficacy of PEGylated liposomal doxorubicin with liposomal minoxidil: comprehensive in silico, in vitro, and in ...). Cancer Weekly. August 19, 2025; p 80.
- [Drug Delivery] (2025;32(1):2536802). Enhancing targeted delivery and efficacy of PEGylated liposomal doxorubicin with liposomal minoxidil: comprehensive in silico, in vitro, and in vivo tumor model studies. Taylor & Francis Ltd, 2-4 Park Square, Milton Park, Abingdon OR14 4RN, Oxon, England.