Targeted delivery of the probiotic Saccharomyces boulardii to the extracellular matrix enhances gut residence time and recovery in murine colitis.

Probiotic and engineered microbe-based therapeutics are an emerging class of pharmaceutical agents. They represent a promising strategy for treating various chronic and inflammatory conditions by interacting with the host immune system and/or delivering therapeutic molecules. Here, we engineered a targeted probiotic yeast platform wherein Saccharomyces boulardii is designed to bind to abundant extracellular matrix proteins found within inflammatory lesions of the gastrointestinal tract through tunable antibody surface display. This approach enabled an additional 24-48 h of probiotic gut residence time compared to controls and 100-fold increased probiotic concentrations within the colon in preclinical models of ulcerative colitis in female mice. As a result, pharmacodynamic parameters including colon length, colonic cytokine expression profiles, and histological inflammation scores were robustly improved and restored back to healthy levels. Overall, these studies highlight the potential for targeted microbial therapeutics as a potential oral dosage form for the treatment of inflammatory bowel diseases.

Fusogenic peptide delivery of bioactive siRNAs targeting CSNK2A1 for treatment of ovarian cancer.

Ovarian cancer has shown little improvement in survival among advanced-stage patients over the past decade. Current treatment strategies have been largely unsuccessful in treating advanced disease, with many patients experiencing systemic toxicity and drug-resistant metastatic cancer. This study evaluates novel fusogenic peptide carriers delivering short interfering RNA (siRNA) targeting casein kinase II, CSNK2A1, for reducing the aggressiveness of ovarian cancer. The peptides were designed to address two significant barriers to siRNA delivery: insufficient cellular uptake and endosomal entrapment. The three peptide variants developed, DIVA3, DIV3H, and DIV3W, were able to form monodisperse nanoparticle complexes with siRNA and protect siRNAs from serum and RNase degradation. Furthermore, DIV3W demonstrated optimal delivery of bioactive siRNAs into ovarian cancer cells with high cellular uptake efficiency and mediated up to 94% knockdown of CSNK2A1 mRNA compared with non-targeting siRNAs, resulting in decreased cell migration and recolonization in vitro. Intratumoral delivery of DIV3W-siCSNK2A1 complexes to subcutaneous ovarian tumors resulted in reduced CSNK2A1 mRNA and CK2α protein expression after 48 h and reduced tumor growth and migration in a 2-week multi-dosing regimen. These results demonstrate the potential of the DIV3W peptide to deliver bioactive siRNAs and confirms the role of CSNK2A1 in cell-cell communication and proliferation in ovarian cancer.

Peptide-based delivery of therapeutics in cancer treatment.

Current delivery strategies for cancer therapeutics commonly cause significant systemic side effects due to required high doses of therapeutic, inefficient cellular uptake of drug, and poor cell selectivity. Peptide-based delivery systems have shown the ability to alleviate these issues and can significantly enhance therapeutic loading, delivery, and cancer targetability. Peptide systems can be tailor-made for specific cancer applications. This review describes three peptide classes, targeting, cell penetrating, and fusogenic peptides, as stand-alone nanoparticle systems, conjugations to nanoparticle systems, or as the therapeutic modality. Peptide nanoparticle design, characteristics, and applications are discussed as well as peptide applications in the clinical space.

Decisional balance among potential implantable cardioverter defibrillator recipients: development of the ICD-decision analysis scale (ICD-DAS).

INTRODUCTION: Sudden cardiac death is a well-documented public health problem and the implantable cardioverter defibrillator (ICD) has demonstrated benefit in reducing mortality. Prospective patients must identify and evaluate the ICD's pros and cons and produce a personal decision. The purpose of this study was to create and evaluate a measure of patient-evaluated pros and cons of the ICD, and its relationship to patient decision regarding ICD implantation. METHODS AND RESULTS: The ICD-decision analysis scale (ICD-DAS) was created and tested in prospective ICD recipients (N = 104). Factor analysis was performed to evaluate interitem relationships, and subsequently, identified subscales; additional psychosocial measures were used to predict the ICD decision. A two-factor measure for ICD decision making was established with two subscales: ICD Pros and ICD Cons. The subscales have high internal consistency and were strong predictors of intent to choose an ICD. Other psychosocial measures were not significantly predictive of ICD Choice, yet simultaneous entry of ICD Pros and Cons subscales resulted in a significant increase in R(2) , F(2, 59) = 19.36, P < 0.001. The full model was significantly greater than zero, F(11, 70) = 5.017, P < 0.001, R(2)  = 0.48. CONCLUSION: The ICD-DAS provides the first empirically tested and clinically useful approach to understanding the specific pros and cons for prospective ICD patients. The measure can assist clinicians with patient-centered discussions regarding sudden cardiac arrest treatments. The ICD-DAS will allow for the provision of tailored education or counseling and may be used to predict postdecision outcomes.