Proof of concept nanotechnological approach to in vitro targeting of malignant melanoma for enhanced immune checkpoint inhibition.

Immunotherapies, including immune checkpoint inhibitors, have limitations in their effective treatment of malignancies. The immunosuppressive environment associated with the tumor microenvironment may prevent the achievement of optimal outcomes for immune checkpoint inhibitors alone, and nanotechnology-based platforms for delivery of immunotherapeutic agents are increasingly being investigated for their potential to improve the efficacy of immune checkpoint blockade therapy. In this manuscript, nanoparticles were designed with appropriate size and surface characteristics to enhance their retention of payload so that they can transmit their loaded drugs to the tumor. We aimed to enhance immune cell stimulation by a small molecule inhibitor of PD-1/PD-L1 (BMS202) using nanodiamonds (ND). Melanoma cells with different disease stages were exposed to bare NDs, BMS202-NDs or BMS202 alone for 6 h. Following this, melanoma cells were co-cultured with freshly isolated human peripheral blood mononuclear cells (hPBMCs). The effects of this treatment combination on melanoma cells were examined on several biological parameters including cell viability, cell membrane damage, lysosomal mass/pH changes and expression of γHA2X, and caspase 3. Exposing melanoma cells to BMS202-NDs led to a stronger than normal interaction between the hPBMCs and the melanoma cells, with significant anti-proliferative effects. We therefore conclude that melanoma therapy has the potential to be enhanced by non-classical T-cell Immune responses via immune checkpoint inhibitors delivered by nanodiamonds-based nanoparticles.

Ultrafast Dynamics of Localized and Delocalized Polaron Transitions in P3HT/PCBM Blend Materials: The Effects of PCBM Concentration.

Nowadays, organic solar cells have the interest of engineers for manufacturing flexible and low cost devices. The considerable progress of this nanotechnology area presents the possibility of investigating new effects from a fundamental science point of view. In this letter we highlight the influence of the concentration of fullerene molecules on the ultrafast transport properties of charged electrons and polarons in P3HT/PCBM blended materials which are crucial for the development of organic solar cells. Especially, we report on the femtosecond dynamics of localized (P2at 1.45 eV) and delocalized (DP2at 1.76 eV) polaron states of P3HT matrix with the addition of fullerene molecules as well as the free-electron relaxation dynamics of PCBM-related states. Our study shows that as PCBM concentration increases, the amplified exciton dissociation at bulk heterojunctions leads to increased polaron lifetimes. However, the increase in PCBM concentration can be directly related to the localization of polarons, creating thus two competing trends within the material. Our methodology shows that the effect of changes in structure and/or composition can be monitored at the fundamental level toward optimization of device efficiency.

Monitoring Charge Exchange in P3HT-Nanotube Composites Using Optical and Electrical Characterisation.

Charge exchange at the bulk heterojunctions of composites made by mixing single wall nanotubes (SWNTs) and polymers show potential for use in optoelectronic devices such as solar cells and optical sensors. The density/total area of these heterojunctions is expected to increase with increasing SWNT concentration but the efficiency of solar cell peaks at low SWNT concentrations. Most researchers use current-voltage measurements to determine the evolution of the SWNT percolation network and optical absorption measurements to monitor the spectral response of the composites. However, these methods do not provide a detailed account of carrier transport at the concentrations of interest; i.e., near or below the percolation threshold. In this article, we show that capacitance-voltage (C-V) response of (metal)-(oxide)-(semiconducting composite) devices can be used to fill this gap in studying bulk heterojunctions. In an approach where we combine optical absorption methods withC-Vmeasurements we can acquire a unified optoelectronic response from P3HT-SWNT composites. This methodology can become an important tool for optoelectronic device optimization.