7.2.1.3　Nanovesicles

Nanovesicles are particles with core-shell structures，whose shells are typically selfassembled from amphiphilic materials such as lipids，polymers，and proteins and the cores are a reservoir of water-rich hydrophilic components.There are three main types of nanovesicles used in melanoma immunotherapy：polymer nanovesicles，polyelectrolyte multilayer nanovesicles，and DNA nanovesicles.Polymer nanovesicles are composed of bilayer membranes of amphiphilic block copolymers，which can encapsulate drugs in the vesicle membrane or aqueous phase core.For example，Moon et al.used monolayer cationic liposomes and hyaluronic acid to construct cross-linked multilayer liposome polymer nanovesicles，which achieved enhanced anti-tumor immune response by synergistic delivery of mode antigen OVA，immunoadjuvant CpG oligonucleotide（CpG ODN）and chemotherapy drug mitoxantrone.Qiu et al.fused PEG with weak cationic polymer to form polymer nanovesicles，which delivered plasmids encoding for IL-12，resulted in improved tumor growth inhibition.Stephan et al.also developed a polymer nanovesicle for in-situ programming of specific T cells by using synthetic DNA nanocarriers.The nanocarriers consist of a DNA-mixed poly（β-amino ester）hydrogel in its core and a PGS shell conjugated to a T cell-targeting ligand.Recently，Wilson et al.constructed an insoluble polymer to increase the activity of the stimulant agonist cyclic guanosine monophosphateadenosine monophosphate（cGAMP），which can inhibit tumor growth，prolong the survival time of the body and increase immune memory.Polyelectrolyte multilayer（PEM）nanovesicles are similar to polymer nanovesicles in that their shells are composed of electrostatic adsorption of polycation and polyanion.Jewell et al.used cationic poly（β-amino ester）and TLRs agonist CpG ODN to prepare the polyelectrolyte multilayer nanovesicles through electrostatic interaction in order to stimulate the body's strong anti-melanoma immune response.DNA nanovesicles are mainly composed of DNA，which can be rolled into a cage-like nanostructure through enzyme action and be used to encapsulate various drug molecules.In 2016，Gu et al.prepared DNA nanococoons from long strand of DNA containing the spacer CpG sequence and the restriction site to encapsulate aPD-1 for prophylactic relapse treatment after tumor resection（Figure 7-4），which significantly inhibited the formation of metastatic nodules in the model of metastatic melanoma.(https://www.daowen.com)