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.
Nasopharyngeal carcinoma (NPC) is a high incidence cancer in southern China and southeast Asia. For the growth and recurrence are in the concealed pharynx and larynx, NPC is difficult to be early diagnosed and effectively treated. Therefore, it is an ideal way to develop strategy for early targeted diagnosis and treatment. R4FLTV, a peptide which can specifically target human nasopharyngeal carcinoma tumor 5-8F, combined with nanoparticle could realize combination of diagnosis and treatment for subcutaneous 5-8F tumor model and lung metastasis in nude mice. By using pull down technology and protein spectrum analysis technique, we found that the ALDH3A2 could be a receptor and molecular marker in the 5-8F cells which targeted by R4FLTV peptide.
KEYWORDS: Nanoparticles, Tissues, Breast cancer, Mammography, Cancer, X-ray computed tomography, 3D acquisition, Luminescence, Fluorescence tomography, Tomography, Tumors, Breast, In vivo imaging, In vitro testing
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.
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