Aspirin-Based Organoiron Dendrimers as Promising Anti-Inflammatory, Anticancer, and Antimicrobial Drugs

Abstract

Designing nanocarriers with actions directed at a specific organ or tissue is a very promising strategy since it can significantly reduce the toxicity of a bioactive drug. In this study, an organometallic dendrimer was used to synthesize a biocompatible drug delivery system by attaching aspirin to the periphery of the dendrimer. Our goal is to enhance the bioavailability and anticancer activity of aspirin and reduce its toxicity through successive generations of organoiron dendrimers. The biological activity of aspirin-based dendrimer complexes was evaluated. The result of antimicrobial activity of the synthesized dendrimers also demonstrated an increase in their antimicrobial activity with increased generation of the dendrimers for most types of microorganisms. This study reveals for the first time that organoiron dendrimers linked with aspirin exhibit an excellent Gram-negative activity comparable to the reference drug Gentamicin. All synthesized dendrimers were tested for their anticancer activity against breast cancer cell lines (MCF-7), hepatocellular cell lines (Hep-G2), and a non-cancer cell line, Human Embryonic Kidney (HEK293), using the MTT cell viability assay and compared against a standard anticancer drug, Doxorubicin. Compounds G3-D9-Asp and G4-D12-Asp exhibited noticeable activity against both cell lines, both of which were more effective than aspirin itself. In addition, the in vivo anti-inflammatory activity and histopathology of swollen paws showed that the designed aspirin-based dendrimers displayed significant anti-inflammatory activity; however, G2-D6-Asp showed the best anti-inflammatory activity, which was more potent than the reference drug aspirin during the same period. Moreover, the coupling of aspirin to the periphery of organoiron dendrimers showed a significant reduction in the toxicity of aspirin on the stomach.

Chitosan–Aspirin Combination Inhibits Quorum-Sensing Synthases (lasI and rhlI) in Pseudomonas aeruginosa

“…We chose to use chitosan as a promising natural biopolymer because of its special qualities, including its innate antimicrobial qualities, natural abundance, adaptability, nontoxicity, and biodegradability [34]. We combined its use with aspirin with its assumed antimicrobial properties to maximize the antibacterial efficacy [35]. We examined their effect phenotypically by detecting the AHL production using A. tumefaciens as a biosensor, and analyzing different virulence factors, e.g., motility, pyocyanin production, and biofilm formation.…”

Engineered Exosomes as Theranostic Platforms for Cancer Treatment

“…Over the past decades, great varieties of exquisite nanomaterials such as liposomes, 9 micelles, 10 dendrimers, 11 mesoporous silica nanoparticles, 12 as well as new-style 2D inorganic nanosheets, 13 have been designed to catalyze the new therapeutic/diagnostic platforms for fighting various cancers. These nanomaterials as drug carriers achieve the drug delivery process by a passive or active target mechanism and unite various therapies, such as chemotherapy, photothermal therapy (PTT), photodynamic therapy (PDT), sonodynamic therapy (SDT) and immunotherapy.…”

Curing inflammatory diseases using phosphorous dendrimers

“…The earliest reports concerned PAMAM dendrimers conjugated with 5‐aminosalicyclic acid, using different spacers containing an azo‐bond, suitable for the triggered release by enzyme azoreductase (Wiwattanapatapee et al, 2003), naproxen (Najlah et al, 2006), or ibuprofen (Kolhe et al, 2006). Two recent papers reported the synthesis of arylether organoiron dendrimers bearing either ibuprofen (Abd‐El‐Aziz, Abdelghani, et al, 2021) or aspirin (Abd‐El‐Aziz, Benaaisha, et al, 2021) as terminal functions, from the first to the fourth generation. Several examples of dendrimers functionalized with corticoids such as methylprednisolone (Inapagolla et al, 2010), triamcinolone acetonide (Cho et al, 2021; Kambhampati et al, 2015), and dexamethasone (Soiberman et al, 2017), have been also reported.…”