Non-specific interactions of antibody-oligonucleotide conjugates with living cells

Antibody-Oligonucleotide Conjugates (AOCs) represent an emerging class of functionalized antibodies that have already been used in a wide variety of applications. While the impact of dye and drug conjugation on antibodies’ ability to bind their target has been extensively studied, little is known about the effect caused by the conjugation of hydrophilic and charged payloads such as oligonucleotides on the functions of an antibody. Previous observations of non-specific interactions of nucleic acids with untargeted cells prompted us to further investigate their impact on AOC binding abilities and cell selectivity. We synthesized a series of single- and double-stranded AOCs, as well as a human serum albumin-oligonucleotide conjugate, and studied their interactions with both targeted and non-targeted living cells using a time-resolved analysis of ligand binding assay. Our results indicate that conjugation of single strand oligonucleotides to proteins induce consistent non-specific interactions with cell surfaces while double strand oligonucleotides have little or no effect, depending on the preparation method.

Recent Advances and Trends in Chemical CPP–Drug Conjugation Techniques

This review summarizes recent developments in conjugation techniques for the synthesis of cell-penetrating peptide (CPP)–drug conjugates targeting cancer cells. We will focus on small organic molecules as well as metal complexes that were used as cytostatic payloads. Moreover, two principle ways of coupling chemistry will be discussed direct conjugation as well as the use of bifunctional linkers. While direct conjugation of the drug to the CPP is still popular, the use of bifunctional linkers seems to gain increasing attention as it offers more advantages related to the linker chemistry. Thus, three main categories of linkers will be highlighted, forming either disulfide acid-sensitive or stimuli-sensitive bonds. All techniques will be thoroughly discussed by their pros and cons with the aim to help the reader in the choice of the optimal conjugation technique that might be used for the synthesis of a given CPP–drug conjugate

Effect of pesticides “Butylcaptax (Russia)” and “Droppa (Russia)” on respiration and oxidative phosphorylation of liver mitochondria of pregnant rats and their embryos

The article provides information on the effect of pesticides - butylcaptax and droppa on respiration and oxidative phosphorylation of liver mitochondria in rat rats and their embryos. It has been shown that butylcaptax and droppa reduce the oxidation of succinate and α-ketoglutarate in the V4*, V3 and Vdnf states and drug conjugation in the liver mitochondria of pregnant animals and their embryos. The most significant inhibition of ADF formation in the respiratory chain of fatal and maternal liver mitochondria occurs via the NAD-dependent pathway, especially when poisoning with butylcaptax on the 19th day of pregnancy. Apparently, inhibition of ADF-stimulated respiration is associated with inhibition of electron transfer along the respiratory chain or is a consequence of inhibition of the transport of phosphate or ADF into mitochondria, which plays a key role in the mechanism of oxidative phosphorylation. A decrease in the conjugation of oxidation and phosphorylation does not create conditions for the accumulation of energy in an utilizable form - in the form of ADF.

GALA peptide improves the potency of nanobody–drug conjugates by lipid-induced helix formation

We generated a potent nanobody–drug conjugation by fusing GALA, which forms helix induced by lipids, enhances membrane binding, and consequently increase cytotoxicity. We provides new insights into the GALA peptide and might boost the field of NDCs.

Characterization and Therapeutic Effect of a pH Stimuli Responsive Polymeric Nanoformulation for Controlled Drug Release

Despite the large number of polymeric nanodelivery systems that have been recently developed, there is still room for improvement in terms of therapeutic efficiency. Most reported nanodevices for controlled release are based on drug encapsulation, which can lead to undesired drug leakage with a consequent reduction in efficacy and an increase in systemic toxicity. Herein, we present a strategy for covalent drug conjugation to the nanodevice to overcome this drawback. In particular, we characterize and evaluate an effective therapeutic polymeric PEGylated nanosystem for controlled pH-sensitive drug release on a breast cancer (MDA-MB-231) and two lung cancer (A549 and H520) cell lines. A significant reduction in the required drug dose to reach its half maximal inhibitory concentration (IC50 value) was achieved by conjugation of the drug to the nanoparticles, which leads to an improvement in the therapeutic index by increasing the efficiency. The genotoxic effect of this nanodevice in cancer cells was confirmed by nucleus histone H2AX specific immunostaining. In summary, we successfully characterized and validated a pH responsive therapeutic polymeric nanodevice in vitro for controlled anticancer drug release.