Nanoghosts derived from mesenchymal stem cells and retaining their unique surface-associated tumor-targeting capabilities were redesigned as a selective and safe universal nonviral gene-therapy platform. pDNA-loaded nanoghosts efficiently targeted and transfected diverse cancer cells, in vitro and in vivo, in subcutaneous and metastatic orthotopic tumor models, leading to no adverse effects. Nanoghosts loaded with pDNA encoding for a cancer-toxic gene inhibited the growth of metastatic orthotopic lung cancer and subcutaneous prostate cancer models and dramatically prolonged the animals' survival.

While individually inefficient against Gram-negative bacteria, in-vitro combinations of rifampin and OAK were mutually synergistic since sub-minimal inhibitory concentrations of one compound have potentiated the other by 2–4 orders of magnitude. Synergy persisted in-vivo as single-dose systemic treatment of Klebsiella infected mice resulted in 10–20% versus 60% survival, respectively accomplished by individual and combined compounds. This outcome was achieved without drug formulation, rather, pharmacokinetic considerations have inspired the therapeutic regimen.

Acidic pH in the tumor microenvironment is associated with cancer metabolism and creates a physiological barrier that prevents from drugs to penetrate cells. Specifically, ionizable weak-base drugs, such as doxorubicin, freely permeate membranes in their uncharged form, however, in the acidic tumor microenvironment these drugs become charged and their cellular permeability is retarded. In this study, 100-nm liposomes loaded with sodium bicarbonate were used as adjuvants to elevate the tumor pH. Combined treatment of triple-negative breast cancer cells (4T1) with doxorubicin and sodium-bicarbonate enhanced drug uptake and increased its anti-cancer activity. In vivo, mice bearing orthotropic 4T1 breast cancer tumors were administered either liposomal or free bicarbonate intravenously. 3.7±0.3% of the injected liposomal dose was detected in the tumor after twenty-four hours, compared to 0.17%±0.04% in the group injected free non-liposomal bicarbonate, a 21-fold increase. Analyzing nanoparticle biodistribution within the tumor tissue revealed that 93% of the PEGylated liposomes accumulated in the extracellular matrix, while 7% were detected intracellularly. Mice administered bicarbonate-loaded liposomes reached an intratumor pH value of 7.38±0.04. Treating tumors with liposomal bicarbonate combined with a subtherapeutic dose of doxorubicin achieved an improved therapeutic outcome, compared to mice treated with doxorubicin or bicarbonate alone. Interestingly, analysis of the tumor microenvironment demonstrated an increase in immune cell' population (T-cell, B-cell and

To address the need for novel alternatives to antibiotics, we attempted to sensitize gram-negative bacilli to innate antibacterial protagonists. We report a lipopeptide-like sequence (C10OOc12O) that inflicted outer membrane damage at a low micromolar range, whereas measurable bacterial growth inhibition in broth medium required >10-fold higher concentrations. In serum, however, C10OOc12O induced antibacterial activity in a manner suppressible by anticomplement antibodies or heat treatment and acted synergistically with exogenous lysozyme in broth and serum media. Upon subcutaneous administration, C10OOc12O exhibited high circulating levels that correlated with significant therapeutic efficacies, using either the mouse peritonitis-sepsis model or the thigh infection model. These findings are consistent with the view that, by damaging the outer membrane, C10OOc12O was able to enhance gram-negative bacilli susceptibility to antibacterial components of the immune humoral arm. Such lipopeptides may therefore be useful in fighting gram-negative bacilli threats through sensitization to endogenous and/or exogenous antibacterial proteins such as lysozyme and complements.

Here we describe a new procedure for ascospore isolation from cultures containing a majority of unsporulated vegetative cells of Saccharomyces cerevisiae. The EZ ascospore isolation procedure relies on the combination of two conventional protocols, diethyl ether treatment and modified zymolyase treatment, allowing a significant increase in the efficiency of ascospore isolation and consequently enabling a large number of meiotic offspring to be efficiently obtained and screened, thus improving the efficacy of genetic research and the genetic selection of S. cerevisiae strains.