Ceftriaxone has been a part of therapeutic regime for combating some of the most aggressive bacterial infections in the last few decades. However, increasing bacterial resistance towards ceftriaxone and other third generation cephalosporin antibiotics has raised serious clinical concerns especially due to their misuse in the COVID-19 era. Advancement in nanotechnology has converted nano-therapeutic vision into a plausible reality with better targeting and reduced drug consumption. Thus, in the present study, gold nanoparticles (GNPs) were synthesized by using ceftriaxone antibiotic that acts as a reducing as well as capping agent. Ceftriaxone-loaded GNPs (CGNPs) were initially characterized by UV-visible spectroscopy, DLS, Zeta potential, Electron microscopy and FT-IR. However, a TEM micrograph showed a uniform size of 21 ± 1 nm for the synthesized CGNPs. Further, both (CGNPs) and pure ceftriaxone were examined for their efficacy against Escherichia coli, Staphylococcus aureus, Salmonella abony and Klebsiella pneumoniae. CGNPs showed MIC50 as 1.39, 1.6, 1.1 and 0.9 µg/mL against E. coli, S. aureus, S. abony and K. pneumoniae, respectively. Interestingly, CGNPs showed two times better efficacy when compared with pure ceftriaxone against the tested bacterial strains. Restoring the potential of unresponsive or less efficient ceftriaxone via gold nanoformulations is the most alluring concept of the whole study. Moreover, applicability of the findings from bench to bedside needs further validation.

Enzymatic gold nanoparticles (B-GNPs) have been synthesized using a natural anticancer agent bromelain (a cysteine protease) and these nanoparticles were used to bioconjugate Cisplatin (highly effective against osteosarcoma and lung cancer). Cisplatin bioconjugated bromelain encapsulated gold nanoparticles (B-C-GNPs) were found profoundly potent against same cancers at much lower concentration with minimum side effects due to the synergistic effect of bromelain. The B-C-GNPs have been observed to inhibit the proliferation of osteosarcoma cell lines Saos-2 and MG-63 with IC50 estimation of 4.51 µg/ml and 3.21 µg/ml, respectively, and against small lung cancer cell line A-549 with IC50 2.5 µg/ml which is lower than IC50 of cisplatin against same cell lines. The B-GNPs/B-C-GNPs were characterized by TEM, UV-Visible spectroscopy, Zeta potential and DLS to confirm the production, purity, crystalline nature, stability of nanoemulsion, size and shape distribution. The change in 2D and 3D conformation of bromelain after encapsulation was studied by Circular Dichroism and Fluorometry, respectively. It was found that after encapsulation, a 19.4% loss in secondary structure was observed, but tertiary structure was not altered significantly and this loss improved the anticancer activity. The confirmation of bioconjugation of cisplatin with B-GNPs was done by UV-Visible spectroscopy, TEM, FTIR, 2D 1H NMR DOSY and ICP-MS. Further, it was found that almost ~4 cisplatin molecules bound with each B-GNPs nanoparticle.

Fungal metabolites, proteins, and enzymes have been rich sources of therapeutics so far. Therefore, in this study, the hypha extract of a newly identified noble fungus (Alternaria sp. with NCBI Accession number: MT982648) was used to synthesize silver nanoparticles (F-AgNPs) to utilize against bacteria, fungi, and lung cancer. F-AgNPs were characterized by using physical techniques, including UV–visible spectroscopy, zeta potential, DLS, XRD, TEM, and HR-TEM. The particles were found to be polydispersed and quasi-spherical in shape under TEM. They had an average size of ~15 nm. The well dispersed particles were found to have consistent crystallinity with cubic phase geometry under XRD and HR-TEM. The presence of different functional groups on the surfaces of biosynthesized F-AgNPs was confirmed by FTIR. The particle distribution index was found to be 0.447 with a hydrodynamic diameter of ~47 d.nm, and the high value of zeta potential (−20.3 mV) revealed the stability of the nanoemulsion. These particles were found to be active against Staphylococcus aureus (multidrug resistance-MDR), Klebsiella pneumonia, Salmonella abony, and Escherichia coli (MDR) with MIC50 10.3, 12.5, 22.69, and 16.25 µg/mL, respectively. Particles also showed inhibition against fungal strains, including A. flavus, A. niger, T. viridens, and F. oxysporium. Their inhibition of biofilm formation by the same panel of bacteria was also found to be very promising and ranged from 16.66 to 64.81%. F-AgNPs also showed anticancer potential (IC50—21.6 µg/mL) with respect to methotrexate (IC50—17.7 µg/mL) against lung cancer cell line A549, and they did not result in any significant inhibition of the normal cell line BEAS-2. The particles were found to alter the mitochondrial membrane potential, thereby disturbing ATP synthesis and leading to high ROS formation, which are responsible for cell membrane damage and release of LDH, intracellular proteins, lipids, and DNA. A high level of ROS also elicits pro-inflammatory signaling cascades that lead to programmed cell death by either apoptosis or necrosis.

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