Construction Of Dual-targeted Virus-like Particles Delivery System And Anti-glioma Research

The blood-brain barrier(BBB)?blood-brain tumor barrier(BBTB)and the poor ability of many drugs to penetrate the barrier limits the treatment of glioblastoma multiforme(GBM)by chemotherapy.Here,we designed a dual-targeted delivery system based on HBc virus-like particles(VLPs)that can target both the brain and the glioma.We inserted a 12-animo acid peptide(denoted as TGN)as a primary targeting ligand on the surface of VLP to target the drug to the brain and through the BBB.On the other VLP surface,the RGD peptide was also inserted by genetic engineering and acted as a secondary targeting ligand for glioma targeting.The two targeted VLPs were heteropolymerized during disassembly and reassembly to achieve both targeting ligand of TGN and RGD on the same VLP(TGN/RGD-VLP).In addition,VLPs encapsulated paclitaxel(PTX)and YAP-siRNA by hydrophobic interaction and electrostatic interaction.Observed by electron microscopy,the VLPs has a complete shape,uniform size and good dispersibility.In in vitro cellular uptake and MTT assays,it was demonstrated that the targeted delivery system promoted uptake of the drug by the cells and kills the tumor cells.Western blot analysis showed that VLPs had higher transfection efficiency and could effectively reduce the expression of YAP protein.And the anti-tumor efficacy in vivo was determined in a nude mouse orthotopic model.It shows that this delivery system could significantly inhibited the proliferation of tumor and had good biocompatibility.All results supported the potential of dual-targeted VLPs as a delivery platform for targeting therapy of tumors.