Enzyme-sensitive nanoparticles, smart TAT and cetuximab conjugated immunoliposomes to overcome multidrug resistance in breast cancer cells

Due to recent advances in the field of small molecule-based drugs, designing an efficient siRNA delivery system seems essential. Here, modified sets of lipids conjugated with cell-penetrating TAT peptide, MMP2 enzyme sensitive moiety, and cetuximab antibodies against the EGF receptor were synthesized, purified and verified on HPLC, TLC, SEM, and DLS analyses. Different cellular and molecular experiments were designed to evaluate the transfection efficiency, targeting properties, and functions, including cytotoxicity assay, resensitization assessments, flow cytometry-based uptake assay, BCRP silencing efficiency, real-time PCR, and western blotting. The final targeted liposomes represented an average diameter of 160 nm; zeta-potential and siRNA encapsulation rates were respectively around -28.9 +/- 3.16 mV and 88.3 +/- 0.9 w/w. The siBCRP carried by the TAT(+)Cetuximab+ liposome led to an increase in the tumoricidal effect of mitoxantrone by a reduction in IC50 value by 4-fold (*** P < 0.001). Flow cytometry results showed that the cellular uptake rate of final immunoliposomes was significantly higher than the naked liposomes (*** P < 0.001). The Targeted siRNA encapsulating liposomes decreased BCRP transcript and protein levels in MCF7-MX cells by 0.24 and 0.2-fold after 48 h, respectively. Due to the silencing results of the BCRP by the encapsulated siRNA and the inhibitory effects of cetuximab on the EGFR, this formulation could widely be utilized as a carrier for tumor-directed gene delivery

Mask assistance to colorimetric sniffers for detection of Covid-19 disease using exhaled breath metabolites

According to World Health Organization reports, large numbers of people around the globe have been infected or died for Covid-19 due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Researchers are still trying to find a rapid and accurate diagnostic method for revealing infected people by low viral load with the overriding goal of effective diagnostic management. Monitoring the body metabolic changes is known as an effective and inexpensive approach for the evaluation of the infected people. Here, an optical sniffer is introduced to detect exhaled breath metabolites of patients with Covid-19 (60 samples), healthy humans (55 samples), and cured people (15 samples), providing a unique color pattern for differentiation between the studied samples. The sniffer device is installed on a thin face mask, and directly exposed to the exhaled breath stream. The interactions occurring between the volatile compounds and sensing components such as porphyrazines, modified organic dyes, porphyrins, inorganic complexes, and gold nanoparticles allowing for the change of the color, thus being tracked as the sensor responses. The assay accuracy for the differentiation between patient, healthy and cured samples is calculated to be in the range of 80%—84%. The changes in the color of the sensor have a linear correlation with the disease severity and viral load evaluated by rRT-PCR method. Interestingly, comorbidities such as kidney, lung, and diabetes diseases as well as being a smoker may be diagnosed by the proposed method. As a powerful detection device, the breath sniffer can replace the conventional rapid test kits for medical applications