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.
In the application of nanotechnology in cancer immunotherapy, antigen presenting cells (APCs, dendritic cells and macrophages) are preferable target due to their endocytic capacity and suppressed phenotype. Recently, we developed a lipid-based core-shell nanocarrier, which is stabilized by changeable fusion peptides and possesses a sub-30 diameter. With the different peptides, the nanoparticles (NPs) could either target to dendritic cells (DCs) in lymph nodes (LNs) or tumor associated macrophages (TAMs) in tumor environment. After subcutaneous injection, the NPs could targeted deliver the encapsulated antigen peptides (APs) and adjuvants (CpG-ODN) to dendritic cells in LNs, and lead to the antigen presenting and activation of cytotoxic T lymphocytes against tumor. In other case, after systemic administration, the immune regulatory molecules were carried by NPs and targeting delivered to specific immunocytes in tumor microenvironment resulting in the immunosuppressive state broken and tumor growth inhibition.
Proc. SPIE. 9709, Biophotonics and Immune Responses XI
KEYWORDS: Breast, 3D acquisition, X-ray computed tomography, Cancer, Breast cancer, Tumors, Tissues, Nanoparticles, Luminescence, Tomography, Mammography, In vivo imaging, In vitro testing, Fluorescence tomography
Breast cancer is one of the most harmful cancers in human. Its early diagnosis is expected to improve the patients’ survival rate. X-ray computed tomography (CT) has been widely used in tumor detection for obtaining three-dimentional information. Fluorescence Molecular Tomography (FMT) imaging combined with near-infrared fluorescent dyes provides a powerful tool for the acquisition of molecular biodistribution information in deep tissues. Thus, the combination of CT and FMT imaging modalities allows us to better differentiate diseased tissues from normal tissues. Here we developed a tumor-targeting nanoparticle for dual-modality imaging based on a biocompatible HDL-mimicking peptide-phospholipid scaffold (HPPS) nanocarrier. By incorporation of CT contrast agents (iodinated oil) and far-infrared fluorescent dyes (DiR-BOA) into the hydrophobic core of HPPS, we obtained the FMT and CT signals simultaneously. Increased accumulation of the nanoparticles in the tumor lesions was achieved through the effect of the tumor-targeting peptide on the surface of nanoparticle. It resulted in excellent contrast between lesions and normal tissues. Together, the abilities to sensitively separate the lesions from adjacent normal tissues with the aid of a FMT/CT dual-model imaging approach make the targeting nanoparticles a useful tool for the diagnostics of breast cancer.