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By adopting a lipoprotein-mimicking peptide self-assembly principle, we created the high density lipoprotein (HDL)-liked peptide-phospholipid scaffold (HPPS), a sub-30 nm core-shell lipid nanoparticle stabilized by apoA-1 mimetic peptides. The HPPS nanocarrier adds a new dimension to the core-shell nanoparticle families particularly valuable for the intracellular delivery of imaging agents, therapeutic peptides or immunomodulators to tumor cells (e.g., melanoma) and immune cells (e.g., dendritic cell and tumor-associated macrophage) in vivo. Recently, we developed HPPS as a carrier to deliver antigen peptides (Aps) to mature dendritic cells (mDCs) in lymph node, which successful elicited desiring anti-tumor immune response. The injection of Ap-HPPS allowed long-term tracking of its flow into lymph nodes using NIR imaging. More importantly, Ap-HPPS exhibited the ability to activate immature DCs and could be directly used as an effective targeting vaccine for in vivo cancer prevention without the need of immunologic adjuvants. We also developed a dual-targeting nanoparticles (M2NPs) for melanoma immunotherapy via delivering small interfering RNA to M2-like tumor-associated macrophages (TAMs). By loading anti-colony stimulating factor-1 receptor (anti-CSF-1R) small interfering RNA (siRNA) on the M2NPs, it specifically blocked the survival signal of M2-like TAMs and deplete them from tumors. Meanwhile, it also inhibited immunosuppressive IL-10 and TGF-β production, and increased immuno-stimulatory cytokinesexpression and CD8+ T cell infiltration in tumor microenvironment. Thus, the dual-targeting property of M2NPs combined with RNA interference provide a potential strategy of molecular-targeted cancer immunotherapy for clinical application.
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