7.2.1.4　Nano-micelles

Nano-micelles are self-assembled structures of amphiphilic polymer molecules in water.The micelles have a variety of morphologies due to the various polymer compositions，lengths and interactions with the carrier mediums.Micelles can encapsulate both hydrophilic and hydrophobic drugs in a single system，which can directly regulate the immune system as a part of a combinatorial approach to reduce tumor burden and/or be used as tumor vaccine nanocarriers against cancer.Li et al.reported a self-assembled micelles based on the prodrug formed by the coupling of PEG and IDO-inhibitor NLG919 and combined with chemotherapeutic drug paclitaxel，which can effectively reverse tumor immunosuppression and significantly improve the therapeutic effect on melanoma.An pH-activated cationic micelle was reported for photodynamic therapy mediated cancer immunotherapy，which was integrated photosensitizer and small interfering RNA（siRNA）to reduced the PD-1 and PDL1 interaction.Compared with photodynamic therapy alone，this multifunctional hybrid micelle remarkably augmented efficacy for melanoma inhibition and distant metastasis（Figure 7-5）.Gao et al.used synthetic micelles not only to enhance antigen delivery and cross-presentation，but also to enhance the anti-tumor immune effect of the interferon gene by stimulating its stimulator pathway and synergistic immune checkpoint inhibition，which can enable the treatment of melanoma.

It is possible to prepare very homogeneous polypeptide-based micelles that can effectively regulate their accumulation，cell uptake and immunogenicity in lymph nodes due to the well controlling of the lengths and polymer sequences of peptides.Moreover，poly peptide-based micelles can easily display antigens along their corona，increasing their abilities of antigen presentation and permit the incorporation of antigens at various locations throughout the micelles，which have been shown to dictate vaccine potency.Ma et al.reported a self-assembled cationic micelle based on poly（ethylene glycol）-b-poly（L-lysine）-bpoly（L-leucine）（PEG-PLL-PLLeu）hybrid polypeptide，which could be used as a simple and effective vaccine delivery system.Furthermore，the polypeptide-based micelle encapsulate both OVA and TLR3-activated polyinosinic acid（PIC）to synergically enhance tumor-specific CTLs responses.(https://www.daowen.com)