Synthesis of chitosan polyethylene glycol antibody complex for delivery of Imatinib in lung cancer cell lines.

Lung cancer is known as the most common cancer. Although the Ramucirumab antibody is a second-line treatment for lung cancer, the high interstitial fluid pressure limits the antibody's performance. In this way, Imatinib is a chemotherapeutic drug to reduce the interstitial fluid pressure. Up to now, unfortunately, both Ramucirumab and imatinib have not been reported in one nanosystem for cancer therapy. To fulfill this shortcoming, this paper aims to design a chitosan nanocarrier that loads imatinib and attaches to Ramucirumab for selective bonding to A549. Therefore, this paper aims to develop a polymeric nanosystem for non-small cell lung cancer (NSCLC) treatment. In first, the chitosan polyethylene glycol nanoparticle is synthesized, loaded with imatinib, and then targeted using Ramucirumab. Afterwards, the CS-PEG-Ab-Im by FTIR, TEM, DLS, zeta potential, and TGA techniques are characterized. The size of CS-PEG-Ab-Im was 25-30 nm, its surface charge was 13.1 mV, and the shape of CS-PEG-Ab-Im was nearly spherical and cylindrical. The therapeutic potential of CS-PEG-Ab-Im was assessed using the A549 cell line. According to the obtained results, the cell viability was 48% after 48 h of treatment of A549 cells using the IC50 concentration of CS-PEG-Ab-Im (100 nanomolar). Moreover, the apoptosis and cell cycle arrest percentages were increased by 3 and 6 times, respectively, as compared to free imatinib. Furthermore, the release rate of imatinib from CS-PEG-Ab-Im in an acidic medium was 17% during 1 h, indicating five times the imatinib release in the natural medium. Eventually, the result of flow cytometry indicates the more apoptotic effect of nanosystem to free imatinib and CS-PEG-Ab. Besides, cell arresting result exhibits the CS-PEG-Ab-Im and causes cell arrested at G1 by %8.17. Thus, it can be concluded that CS-PEG-Ab-Im can be an ideal nanosystem in NSCLC treatment.

Margetuximab conjugated-PEG-PAMAM G4 nano-complex: a smart nano-device for suppression of breast cancer.

Abstract: Breast cancer due to its high incidence and mortality is the second leading cause of death among females. On the other hand, nanoparticle-based drug delivery is one of the most promising approaches in cancer therapy, nowadays. Hence, margetuximab- and polyethylene glycol-conjugated PAMAM G4 dendrimers were efficiently synthesized for targeted delivery of quercetin (therapeutic agent) to MDA-MB-231 breast cancer cells. Synthesized nano-complexes were characterized using analytical devices such as FT-IR, TGA, DLS, Zeta potential analyzer, and TEM. The size less than 40 nm, - 18.8 mV surface charge, efficient drug loading capacity (21.48%), and controlled drug release (about 45% of drug release normal pH after 8 h) were determined for the nano-complex. In the biomedical test, the cell viability was obtained 14.67% at 24 h of post-treatment for 800 nM concentration, and IC50 was ascertained at 100 nM for the nano-complex. The expression of apoptotic Bax and Caspase9 genes was increased by more than eightfolds and more than fivefolds after treatment with an optimal concentration of nanocarrier. Also, more than threefolds of cell cycle arrest was observed at the optimal concentration synthetics, and 27.5% breast cancer cell apoptosis was detected after treatment with 100 nM nano-complex. These outputs have been indicating the potential capacity of synthesized nano-complex in inhibiting the growth of breast cancer cells.

Non-coding RNA in SARS-CoV-2: Progress toward therapeutic significance.

The recently developed pathogenic virus, SARS-CoV-2, was found in the Hubei Province, China. Giving rise to a broad spectrum of symptoms, SARS-CoV-2 rapidly spread across the globe, causing multi-systemic and dangerous complications, with death in extreme cases. Thereby, the number of research cases increases every day on preventing infection and treating its resulting damage. Accumulating evidence suggests noncoding RNAs (ncRNAs) are necessary for modifying virus infection and antiviral immune reaction, along with biological processes regulating SARS-CoV-2 and subsequent disease states. Therefore, understanding these mechanisms might provide a further understanding of the pathogenesis and feasible therapy alternatives against SARS-CoV2. Consequently, the molecular biology of SARS-CoV-2, ncRNA's role in its infection, and various RNA therapy tactics against the virus have been presented in this review section.

Evaluation of the Association Between Serum Levels of Testosterone and Prolactin With 6- Hydroxydopamine-Induced Parkinsonism in Male Rats.

INTRODUCTION: Parkinson's Disease (PD) associates with changes in sex hormones; however, it remains unknown whether this is either a cause for or a result of the disease. To further evaluate it, we investigated if the development of 6-Hydroxydopamine (6-OHDA)-induced Parkinsonism changes the serum levels of testosterone and prolactin or not. METHODS: 6-OHDA was injected into the medial forebrain bundle using stereotaxic surgery. The development of Parkinsonism was evaluated by apomorphine-induced rotational test and the immunofluorescence labeling of Dopaminergic (DA) neurons in substantia nigra. The necessary blood samples were collected before the toxin and in the third and sixth weeks afterward. The hormones levels were determined using Enzyme-Linked Immunosorbent Assay (ELISA) kits. RESULTS: The severity of rotations was different among 6-OHDA-treated rats; accordingly, they were divided into two subgroups of severe and mild parkinsonian rats. The degeneration of DA neurons was observed in both subgroups; however, it was significantly less in the mild group. In the sixth week after the toxin, testosterone level increased but only in the severe subgroup. Prolactin increased in both subgroups in the third week after the toxin but returned to normal in the sixth week. There was no association between the pre-toxin levels of these hormones and the intensity of Parkinsonism. CONCLUSION: Our findings indicated that the development of 6-OHDA-induced Parkinsonism increases the serum levels of testosterone and prolactin. Increased prolactin occurred earlier and was observed in rats with less DA neuronal loss. Therefore, prolactin levels can predict the death of DA neurons before the clinical signs of PD were revealed.