Nanoplasmonic Approaches for Sensitive Detection and Molecular Characterization of Extracellular Vesicles.

All cells release a multitude of nanoscale extracellular vesicles (nEVs) into circulation, offering immense potential for new diagnostic strategies. Yet, clinical translation for nEVs remains a challenge due to their vast heterogeneity, our insufficient ability to isolate subpopulations, and the low frequency of disease-associated nEVs in biofluids. The growing field of nanoplasmonics is poised to address many of these challenges. Innovative materials engineering approaches based on exploiting nanoplasmonic phenomena, i.e., the unique interaction of light with nanoscale metallic materials, can achieve unrivaled sensitivity, offering real-time analysis and new modes of medical and biological imaging. We begin with an introduction into the basic structure and function of nEVs before critically reviewing recent studies utilizing nanoplasmonic platforms to detect and characterize nEVs. For the major techniques considered, surface plasmon resonance (SPR), localized SPR, and surface enhanced Raman spectroscopy (SERS), we introduce and summarize the background theory before reviewing the studies applied to nEVs. Along the way, we consider notable aspects, limitations, and considerations needed to apply plasmonic technologies to nEV detection and analysis.

Repurposing ospemifene for potentiating an antigen-specific immune response.

OBJECTIVE: Ospemifene, an estrogen receptor agonist/antagonist approved for the treatment of dyspareunia and vaginal dryness in postmenopausal women, has potential new indications as an immune modulator. The overall objective of the present series of preclinical studies was to evaluate the immunomodulatory activity of ospemifene in combination with a peptide cancer vaccine. METHODS: Immune regulating effects, mechanism of action and structure activity relationships of ospemifene and related compounds were evaluated by examining expression of T-cell activating cytokines in vitro, and antigen-specific immune response and cytotoxic T-lymphocyte activity in vivo. The effects of ospemifene (OSP) on the immune response to a peptide cancer vaccine (PV) were evaluated after chronic [control (n = 22); OSP 50 mg/kg (n = 16); PV (n = 6); OSP+PV (n = 11)], intermittent [control (n = 10); OSP 10 and 50 mg/kg (n = 11); PV (n = 11); combination treatment (n = 11 each dose)] and pretreatment [control; OSP 100 mg/kg; PV 100 µg; combination treatment (n = 8 all groups)] ospemifene oral dosing schedules in a total of 317 mixed-sex tumor-bearing and nontumor-bearing mice. RESULTS: The results showed that ospemifene induced expression of the key TH1 cytokines interferon gamma and interleukin-2 in vitro, which may be mediated by stimulating T-cells through phosphoinositide 3-kinase and calmodulin signaling pathways. In combination with an antigen-specific peptide cancer vaccine, ospemifene increased antigen-specific immune response and increased cytotoxic T-lymphocyte activity in tumor-bearing and nontumor-bearing mice. The pretreatment, intermittent, and chronic dosing schedules of ospemifene activate naive T-cells, modulate antigen-induced tolerance and reduce tumor-associated, pro-inflammatory cytokines, respectively. CONCLUSIONS: Taken together, ospemifene's dose response and schedule-dependent immune modulating activity offers a method of tailoring and augmenting the efficacy of previously failed antigen-specific cancer vaccines for a wide range of malignancies.