Current Medicinal Chemistry - Volume 22, Issue 29, 2015

Toll like receptors (TLRs) are a family of transmembrane proteins which play a key role in innate immunity. When TLRs come into contact with a potential threat, they initiate a signaling cascade leading to release of cytokines and chemokines, maturation of antigen presenting cells and immune activation. Molecules which can activate TLRs may be utilized for vaccine development and act as vaccine adjuvants. Adjuvants can facilitate production of more effective vaccines based on antigens produced by recombinant techniques or by DNA vaccines, which are often poorly immunogenic since they lack the endogenous innate immunostimulatory components of the pathogen. In this paper the structural properties of such prospective compounds are thoroughly discussed.

Gene therapy requires safe and effective vectors to deliver genes to their target site of action. Non-viral gene delivery systems have attracted growing attention due to their low toxicity, low immunogenicity and ease of production compared to viral vectors. Most non-viral gene delivery systems enter cells via endocytic pathways, and their escape from endosomes is therefore crucial for successful transfection. Several reagents have been developed to promote endosomal escape, including peptides, polymers and lipids. Among these, endosome-disrupting peptides have been used in many studies, and have proven to be one of the most promising approaches to overcome endosomal entrapment and lysosomal degradation. This review provides an up-to-date summary of strategies for enhancing endosomal escape, with a focus on the modification of endosome-disrupting peptides to further increase the efficient delivery of oligonucleotides.

Cancer has been affecting a growing number of children, adolescents and adult males in reproductive age. Male reproductive potential is adversely affected by chemotherapeutic drugs and patients are at risk for prolonged infertility. Fertility recovery is related to the chemotherapeutic agent and dosage used, being thus difficult to predict. As a result, there is a strong need to identify a natural or synthetic compound that is able to preserve male fertility without interfering with the efficacy of the chemotherapeutic regimen. New procedures, as well as several drugs, are being investigated to assess their efficiency in protecting male reproductive functions from the chemotherapy side-effects. This review provides an overview of the wide range of chemotherapeutic drugs regularly used in cancer treatment and their detrimental effects on male fertility. In addition, it also assesses the existing protector agents for male fertility and their usefulness in preserving and protecting male reproductive functions exposed to chemotherapeutics. Several protector agents for male fertility are being studied, and results are promising. Nonetheless, further research must be implemented to identify a supplemental therapy that addresses the multiple side effects of chemotherapy on male reproductive function. Until such therapy is discovered, it is fundamental that all fertility preservation options are discussed with patients, before treatment is initiated, to assure parenthood.

Early detection of pancreatic cancer has been a long-standing challenge in determining prognosis and management of the deadly disease. Although the incidence of pancreatic cancer is low (2% of all malignancies), it is the fourth leading cause of deaths attributable to cancer in the U.S. A major cause for the high mortality rate, which exceeds 85%, is the difficulty in diagnosing the disease early in its development. The relative lack of reliable diagnostic tools to screen patients who are asymptomatic prior to the aggressive progression of disease has been the primary contributing factor in the high mortality rate in this patient population. Indeed, 80-90% of patients with pancreatic cancer have relatively small unresectable tumors at the time of diagnosis. Therefore, there is an unmet need for a highly sensitive diagnostic imaging modality to detect early-stage pancreatic cancer, as this may save the lives of many thousands of patients. Many literature reviews have been published on various aspects of pancreatic cancer, including biology, screening, and therapy; however, limited information is available on early detection, especially the use of highly sensitive modalities such as positron emission tomography (PET). Current [18F]FDG/PET imaging combined with CT (PET/CT) lacks the necessary sensitivity and specificity for detection of small lesions (~2-3 mm) of pancreatic cancer that may be resectable and curable. Furthermore, accumulation of [18F]FDG in inflammatory tissue is a major problem; therefore, an appropriate PET tracer that is both highly sensitive and specific for carcinoma is necessary for PET imaging of early stage pancreatic cancer. This review focuses on early detection of pancreatic cancer by PET, including new targets and the development and application of new PET tracers.

Multimodal imaging agents were first introduced a decade ago and consist of a targeting moiety that is dual-labeled with radioactive and fluorescent contrast. These compounds allow whole-body and intraoperative imaging to be performed through administration of a single agent and provide complementary diagnostic information that can be used to guide tumor resection. Since their initial evaluation, interest in dual-labeled agents has continued to grow and their design has subsequently evolved alongside the development of novel chelating agents, improved fluorophores, and highly selective coupling techniques for bioconjugate formation. In this review, will discuss how changes in the labeling components and schemes for multimodal agent development have impacted imaging performance and will focus on antibody- and peptide-based agents as models for dual labeling. We will also describe the growing role of modular dual labeling strategies as well as direct labeling methods using radiohalogens.