Nano-enabled bioanalytical approaches to ultrasensitive detection of low abundance single nucleotide polymorphisms

Single nucleotide polymorphisms (SNPs) constitute the most common types of genetic variations in the human genome. A number of SNPs have been linked to the development of life threatening diseases including cancer, cardiovascular diseases and neurodegenerative diseases. The ability for ultrasensitive and accurate detection of low abundant disease-related SNPs in bodily fluids (e.g. blood, serum, etc.) holds a significant value in the development of non-invasive future biodiagnostic tools. Over the past two decades, nanomaterials have been utilized in a myriad of biosensing applications due to their ability of detecting extremely low quantities of biologically important biomarkers with high sensitivity and accuracy. Of particular interest is the application of such technologies in the detection of SNPs. The use of various nanomaterials, coupled with different powerful signal amplification strategies, has paved the way for a new generation of ultrasensitive SNP biodiagnostic assays. Over the past few years, several ultrasensitive SNP biosensors capable of detecting specific targets down to the ultra-low regimes (ca. aM and below) and therefore holding great promises for early clinical diagnosis of diseases have been developed. This mini review will highlight some of the most recent, significant advances in nanomaterial-based ultrasensitive SNP sensing technologies capable of detecting specific targets on the attomolar (10-18 M) regime or below. In particular, the design of novel, powerful signal amplification strategies that hold the key to the ultrasensitivity is highlighted

A Comparative Parallel Study of Pharmacokinetics and Immunogenicity Following Single Intravenous Administration of Bevacizumab Biosimilar RPH-001 (Manufactured by R-Pharm Group, Russia) and Avastin® (Manufactured by F. Hoffmann-La Roche Ltd., Switzerland) in Healthy Male Volunteers

Introduction. Bevacizumab is a monoclonal IgG1 antibody that binds to and inhibits the biologic activity of human vascular endothelial growth factor (VEGF). Bevacizumab is used as a targeted monoor combination therapy for different solid tumors. Phase I clinical trial was performed to assess pharmacokinetics (PK) and immunogenicity of bevacizumab drugs. For this study 80 healthy male volunteers were recruited and randomized to either Avastin or RPH-001 group.Aim. To assess and compare pharmacokinetics and immunogenicity (safety) following single intravenous administration of Avastin® (manufactured by F. Hoffmann-La Roche Ltd., Switzerland) and bevacizumab biosimilar RPH-001 (manufactured by R-Pharm Group, Russia).Materials and methods. Bevacizumab quantitation and quasi-quantitative anti-bevacizumab antibodies detection in human blood serum were carried out using photometric ELISA. Two different methods were successfully validated.Results and discussion. Bevacizumab quantitation method was validated for selectivity and specificity, calibration curve, sensitivity, accuracy and precision, minimal required dilution, dilution linearity and stability. The anti-bevacizumab antibodies detection method was validated for cut-point (with normalization factor calculation), selectivity, sensitivity, precision, drug tolerance, dilution linearity, matrix effect (in case of serum hemolysis), and stability. The validated methods were successfully applied to pharmacokinetic and immunogenicity assessment of bevacizumab drugs.Conclusion. The results of the PK-study showed that test and reference bevacizumab drugs were equivalent. Immunogenicity study did not show any evidence of anti-bevacizumab antibodies in blood serum samples