7.2.1.1　Solid NPs

Solid NPs have been extensively researched in melanoma immunotherapy to enhance the anti-melanoma immune response.Among them，solid poly（lactic-co-glycolic acid）（PLGA）NPs have become an important material for drug delivery and immunotherapy due to their good biosafety，synthetic ability and adaptability.A series of tumor immunotherapy strategies have been developed based on PLGA NPs for its easiness to bind and modify drugs，cytokines，antibodies and other immunomodulators.

On the one hand，PLGA NPs can encapsulate antigens to form anti-tumor vaccines，thereby improving the efficiency of antigen presentation and the stability in physiological environment.Sasada et al.used PLGA NPs to co-deliver melanoma-specific antigen peptides（TRP2 and GP100）and Freund's complete adjuvant（FCA）to induce a strong CTLs response in melanoma-bearing mice.PEG modified PLGA NPs loaded with mode antigen ovalbumin（OVA），immunoadjuvant muscle cytidine acid（polyinosinic：polycytidylic acid，poly（I：C））and Resiquimod（TLR7/8 agonist，R848），can trigger endosomal TLRs to induce an effective anti-tumor immune response in mice bearing OVA-expressing melanoma tumors.On the other hand，PLGA NPs can load with small molecule inhibitors to realize the immunotherapy of melanoma.In 2010，Lavasanifar et al.used PLGA NPs to deliver JSI-124，a small molecule inhibitor of STAT 3，to tumor cells and immunosuppressed dendritic cells，thereby modulating the anti-melanoma immune response in tumor cells and immunosuppressed dendritic cells in vitro through JSI-124.Moreover，PLGA NPs can deliver anticancer drug paclitaxel（PTX）and non-toxic derivative of lipopolysaccharide（SP-LPS）for the combination with chemotherapy and immunotherapy to enhance its killing effect on melanoma cells in vitro.Furthermore，PLGA NPs loaded with TLR7/8 agonists can enable DCs to enhance the expression of co-stimulatory molecules and antigen presentation through the MHC-Ⅰ　process，thereby achieving significant effects on the prevention and treatment melanoma models.Besides，PLGA NPs can deliver immune checkpoint inhibitors.Wang et al.demonstrated that PLGA NPs co-delivered aPD-1 and anti-OX40，a stimulant antibody that activates the costalized receptor，has therapeutic results in two melanoma models.In 2017，Goldberg et al.developed aPD-1-decorated PLGA NPs that target T cells and simultaneously release R848 and SD-208（transforming growth factor-β（TGF-β）receptor inhibitors）to break the immunosuppressive effects of TGF-β and potentiate its anti-tumor response.In addition，PLGA NPs can also be used to regulate tumor-associated macrophages（TAMs）to activate anti-tumor immunity.In 2018，Chen et al.employed PLGA NPs to deliver reactive oxygen species（ROS）generating products to polarize TAMs toward the M1 phenotype and subsequently recruit coordinated CTLs to effectively prevent tumor progression and recurrence.

What's more，PLGA NPs incorporated therapeutic agents to realize the combination of tumor immunotherapy with chemotherapy，photothermal therapy，photodynamic therapy，radiation therapy and other tumor treatment strategies，so as to achieve effective treatment of melanoma.Several research groups have added photothermal conversion materials to PLGA NPs to achieve the combination of photothermal therapy（PTT）and immune therapy，which can be further combined with immune checkpoint inhibitors for the treatment of melanoma.In 2018，You et al.reported a therapeutic strategy combining PD-1 blocker and photothermal ablation for melanoma，where aPD-1 peptide and hollow gold nanoshells were co-encapsulated into PLGA NPs，which showed a strong anti-tumor effect，eliminated most of the primary tumors and also significantly inhibited the growth of distally untreated primary tumors.In 2019，Yang et al.constructed multifunctional PLGA NPs with core-shell structure encapsulated with aPD-1 and perfluorinated pentane（PFP）liquid in the core.The modification of PLGA NPs with polyethylene glycol（PEG）and gly-argy-asp-ser（GRGDS）peptides act as encapsulating shell，while iron oxide NPs were loaded in the shell.The hybrid nanoparticles showed an excellent synergistic effect in the treatment of melanoma.In 2018，Kim et al.designed a layer-by-layer hybrid PLGA NP encapsulated the infrared dye IR-780 iodide and the chemotherapy drug imatinib to achieve the anti-tumor effect of PTT and PDT as well as the down-regulation of Treg in tumors.In 2017，Wang et al.reported a synergistic strategy of tumor radiation therapy and immunotherapy.The tumor was first treated with radiation，then the released tumor antigens were selectively captured with PLGA NPs for DCs presentation，resulted in activating the body's antigen-specific antitumor response（Figure 7-3）.Combined with the immune checkpoint inhibitor antiprogrammed cell death protein 1（aPD-1），significant distal tumor ablation can be achieved.(https://www.daowen.com)

However，the degradation products of PLGA are acidic，which may reduce the stability of the encapsulated drugs and cause mild inflammation in adjacent tissues.In addition to PLGA NPs，there are many other solid NPs that have been applied in immunotherapy，such as polypropylene sulfide（PPS）NPs，polypropylene poly（ethylene glycol）（PPG）NPs，polycaprolactone（PCL）NPs，and PEG NPs.PPS is a kind of mechanically robust and organic thermoplastic material and has been a promising oxidation-responsive material for drug delivery applications due to the degradation by ROS.Hubbell et al.reported that PPS NPs with a particle size of 30 nm could effectively target DCs（CD11c+）in lymph nodes，thus accumulating in tumor draining lymph nodes.PPS NPs co-coated with melanoma antigen and immunoadjuvants CpG or paclitaxel can increase tumor antigen specific CD8+T cells，thus stimulating an effective anti-tumor immune response and inhibiting melanoma growth.Florindo et al.constructed mannosel-functionalized aliphatic polyester-based NPs that co-loaded melanoma-associated antigens and TLR ligands poly（I：C）and CpG oligonucleotide for targeting to antigen-presenting cells，which effectively enhanced the Thl immune response and effectively inhibited the growth of melanoma in the treatment and prevention model.