Study On FMDV Virus-Like Particle As A Targeted Anti-cancer Drug Delivery

Virus-like particles (VLPs) are multi-protein structures that mimic the organization and conformation of authentic native viruses but lack the viral genome, which potentially can be safer and cheaper vaccine candidates. A handful of prophylactic VLPs-based vaccines are currently commercialized worldwide:hepatitis B virus VLPs vaccine and human papillomavirus VLPs vaccine. Other VLPs-based vaccine candidates are in clinical trials or undergoing preclinical evaluation, such as, influenza virus, parvovirus, norwalk and various chimeric VLPs. All of the achievement making the VLPs vaccine a safe new-generation vaccines against prevalent and emergent diseases. Up to now, for more than 100 kinds of VLPs which infecting humans and other animals have been produced on different stages.In addition to the application of VLPs on a vaccine, the unique spatial conformation also makes it a very good biological carrier, VLPs as a kind of nanomaterials have many unique advantages:VLPs formed by the combination of the capsid protein with the diameter between 20～150 nm in general, owning the characteristics of nano-scale materials; VLPs hold many decorative carboxylate groups on the surface, which makes them as a promising delivery and imaging for therapeutic agents and label reagents through covalent coupling. VLPs have stable structure, especially those from the dodecahedral or icosahedral structure, such as hepatitis B virus, human papilloma virus, phage MS2, Qβ phage, most of them assembled by a single coat protein, which can withstand a large range of the pH value and temperature changes. On the surface of VLPs exploiting many amino acid residues, these residues can react with nucleic acid, protein and small molecule drugs through the chemical bond links, and thus can become a stable complex for delivery.Side-effect of anticancer drug is an important limited reason during the anticancer therapy, so it’s the trend that alter the pharmacokinetic properties by enhancing their accumulation in tumors and reducing non-selective distribution to normal tissues to improve the therapeutic efficacy of anticancer agents. The targeted therapy of tumor is a modern treatment of cancer. Compared to traditional chemical treatment, targeted therapy has lower side effects and higher affection. The action sites of molecular targeted therapy are the components which play roles in the progress of carcinogenesis, such as gene, receptor, and the key enzymes. Nowadays, several mechanisms f carcinogenesis have been developed clearly, and drugs which are targeted at these pathways have also been introduced into clinical trial.In this study, to improve the targeting ability of doxorubicin (DOX) drug, we produced FMDV-VLPs as SUMO fusion protein in E.coli, the VLPs are loaded with a large payload of an anticancer drug DOX through a hydrazone by chemical conjugation. FMDV-VLPs surface loop contain conserved RGD integrin-binding motif, which make FMDV specifically attach the integrin receptors. We show that targeting of FMDV-VLPs-DOX (FVD) complex via RGD-receptor binding results in attachment, endocytosis, intracellular degradation, and drug release, leading to growth inhibition of the target cells in vitro. The FMDV-VLPs-DOX has excellent biocompatibility and biodegradability. FMDV VLPs can be prepared in large scale from E.Coli by our method, which may find practical applications in biomedicine. FMDV-VLPs could be a promising platform for specific targeting delivery system.