Tumor-targeting cell membrane-coated nanorings for magnetic-hyperthermia-induced tumor ablation.

Magnetic hyperthermia has attracted considerable attention for efficient cancer therapy because of its noninvasive nature, deep tissue penetration, and minimal damage to healthy tissues. Herein, we have fused cancer cell membrane fragments with lipids and cloaked them on magnetic nanorings to form targeted Fe nanorings (TF) for tumor-targeted magnetic hyperthermia-induced tumor ablation. In our approach, cell membrane fragments from cancer cells were fused with lipids to form vesicles, which could efficiently encapsulate magnetic nanorings, thereby forming TF. We observed that TF have high tumor uptake via homotypic targeting, where cancer cells take up TF through membrane fusion. Under an external alternating magnetic field (AMF), TF accumulated in the tumors are heated, driving magnetic-hyperthermia-induced tumor cell death. Our in vitro studies show that self-targeting TF efficiently localized in cancer cells and induced cell death with an AMF, which was shown by a live/dead assay. Our findings demonstrate the potential of TF in tumor ablation, thereby making them promising and efficient nanosystems for tumor-targeted theranostics.

The Emerging Role of Raman Spectroscopy as an Omics Approach for Metabolic Profiling and Biomarker Detection toward Precision Medicine.

Omics technologies have rapidly evolved with the unprecedented potential to shape precision medicine. Novel omics approaches are imperative toallow rapid and accurate data collection and integration with clinical information and enable a new era of healthcare. In this comprehensive review, we highlight the utility of Raman spectroscopy (RS) as an emerging omics technology for clinically relevant applications using clinically significant samples and models. We discuss the use of RS both as a label-free approach for probing the intrinsic metabolites of biological materials, and as a labeled approach where signal from Raman reporters conjugated to nanoparticles (NPs) serve as an indirect measure for tracking protein biomarkers in vivo and for high throughout proteomics. We summarize the use of machine learning algorithms for processing RS data to allow accurate detection and evaluation of treatment response specifically focusing on cancer, cardiac, gastrointestinal, and neurodegenerative diseases. We also highlight the integration of RS with established omics approaches for holistic diagnostic information. Further, we elaborate on metal-free NPs that leverage the biological Raman-silent region overcoming the challenges of traditional metal NPs. We conclude the review with an outlook on future directions that will ultimately allow the adaptation of RS as a clinical approach and revolutionize precision medicine.

Targeting pancreatic cancer with magneto-fluorescent theranostic gold nanoshells.

AIM: We report a magneto-fluorescent theranostic nanocomplex targeted to neutrophil gelatinase-associated lipocalin (NGAL) for imaging and therapy of pancreatic cancer. MATERIALS & METHODS: Gold nanoshells resonant at 810 nm were encapsulated in silica epilayers doped with iron oxide and the near-infrared (NIR) dye indocyanine green, resulting in theranostic gold nanoshells (TGNS), which were subsequently conjugated with antibodies targeting NGAL in AsPC-1-derived xenografts in nude mice. RESULTS: Anti-NGAL-conjugated TGNS specifically targeted pancreatic cancer cells in vitro and in vivo providing contrast for both NIR fluorescence and T2-weighted MRI with higher tumor contrast than can be obtained using long-circulating, but nontargeted, PEGylated nanoparticles. The nanocomplexes also enabled highly specific cancer cell death via NIR photothermal therapy in vitro. CONCLUSION: TGNS with embedded NIR and magnetic resonance contrasts can be specifically targeted to pancreatic cancer cells with expression of early disease marker NGAL, and enable molecularly targeted imaging and photothermal therapy.

A molecularly targeted theranostic probe for ovarian cancer.

Overexpression of the human epidermal growth factor receptor (HER) family has been implicated in ovarian cancer because of its participation in signaling pathway regulating cellular proliferation, differentiation, motility, and survival. Currently, effective diagnostic and therapeutic schemes are lacking for treating ovarian cancer, and consequently ovarian cancer has a high mortality rate. Although HER2 receptor expression does not usually affect the survival rates of ovarian cancer to the same extent as in breast cancer, it can be used as a docking site for directed nanotherapies in cases with de novo or acquired chemotherapy resistance. In this study, we have exploited a novel gold nanoshell-based complex (nanocomplex) for targeting, dual modal imaging, and photothermal therapy of HER2-overexpressing and drug-resistant ovarian cancer OVCAR3 cells in vitro. The nanocomplexes are engineered to simultaneously provide contrast as fluorescence optical imaging probe and a magnetic resonance imaging agent. Immunofluorescence staining and magnetic resonance imaging successfully show that nanocomplex-anti-HER2 conjugates specifically bind to OVCAR3 cells as opposed to the control, MDA-MB-231 cells, which have low HER2 expression. In addition, nanocomplexes targeted to OVCAR3 cells, when irradiated with near-IR laser, result in selective destruction of cancer cells through photothermal ablation. We also show that near-IR light therapy and the nanocomplexes by themselves are noncytotoxic in vitro. To the best of our knowledge, this is the first successful integration of dual modal bioimaging with photothermal cancer therapy for treatment of ovarian cancer. Based on their efficacy in vitro, these nanocomplexes are highly promising for image-guided photothermal therapy of ovarian cancer, as well as other HER2-overexpressing cancers. Mol Cancer Ther; 9(4); 1028-38. (c)2010 AACR.