Modern oncotherapy approaches are based on inducing controlled apoptosis in tumor cells. Although a number of apoptosis-induction approaches are available, site-specific delivery of therapeutic agents still remain the biggest hurdle in achieving the desired cancer treatment benefit. Additionally, systemic treatment-induced toxicity remains a major limiting factor in chemotherapy. To specifically address drug-accessibility and chemotherapy side effects, oncolytic virotherapy (OV) has emerged as a novel cancer treatment alternative. In OV, recombinant viruses with higher replication capacity and stronger lytic properties are being considered for tumor cell-targeting and subsequent cell lysing. Successful application of OVs lies in achieving strict tumor-specific tropism called oncotropism, which is contingent upon the biophysical interactions of tumor cell surface receptors with viral receptors and subsequent replication of oncolytic viruses in cancer cells. In this direction, few viral vector platforms have been developed and some of these have entered pre-clinical/clinical trials. Among these, the Vesicular stomatitis virus (VSV)-based platform shows high promise, as it is not pathogenic to humans. Further, modern molecular biology techniques such as reverse genetics tools have favorably advanced this field by creating efficient recombinant VSVs for OV; some have entered into clinical trials. In this review, we discuss the current status of VSV based oncotherapy, challenges, and future perspectives regarding its therapeutic applications in the cancer treatment.

In this study, we investigated the effects of membrane cholesterol content on the mechanical properties of cell membranes by using optical tweezers. We pulled membrane tethers from human embryonic kidney cells using single and multi-speed protocols, and obtained time-resolved tether forces. We quantified various mechanical characteristics including the tether equilibrium force, bending modulus, effective membrane viscosity, and plasma membrane–cytoskeleton adhesion energy, and correlated them to the membrane cholesterol level. Decreases in cholesterol concentration were associated with increases in the tether equilibrium force, tether stiffness, and adhesion energy. Tether diameter and effective viscosity increased with increasing cholesterol levels. Disruption of cytoskeletal F-actin significantly changed the tether diameters in both non-cholesterol and cholesterol-manipulated cells, while the effective membrane viscosity was unaffected by F-actin disruption. The findings are relevant to inner ear function where cochlear amplification is altered by changes in the membrane cholesterol content.

Fluorescence from fluorophores embedded in a turbid medium like biological tissue gets strongly modulated by the wavelength dependent absorption and scattering properties of tissue. This makes it extremely difficult to extract valuable biochemical information from tissue which is present in the intrinsic line shape and intensity of fluorescence from tissue fluorophores. We present an experimental approach to remove the distorting effect of scattering and absorption on intrinsic fluorescence of fluorophores embedded in a turbid medium like tissue. The method is based on simultaneous measurement of polarized fluorescence and polarized elastic scattering spectra from a turbid medium. The polarized fluorescence normalized by the polarized elastic scattering spectra (in the wavelength range of fluorescence emission) was found to be free from the distorting effect of absorption and scattering properties of the medium. The applicability range of this technique to recover intensity and line shape information of intrinsic fluorescence has been investigated by carrying out studies on a variety of tissue phantoms having different absorption and scattering properties. The results obtained show that this technique can be used to recover intrinsic line shape and intensity information of fluorescence from fluorophores embedded in a scattering medium for the range of optical transport parameters typically found in biological tissue.

We report the first proof-of-principle demonstration of photoacoustic imaging using a contrast agent composed of a plant virus protein shell, which encapsulates indocyanine green (ICG), the only FDA-approved near infrared chromophore. These nano-constructs can provide higher photoacoustic signals than blood in tissue phantoms, and display superior photostability compared to non-encapsulated ICG. Our preliminary results suggest that the constructs do not elicit an acute immunogenic response in healthy mice.