Novel Carbazole (Cbz)-Based Carboxylated Functional Monomers: Design, Synthesis, and Characterization.

A series of novel functional carbazole (Cbz)-based carboxylated monomers were synthesized and characterized. A Clauson-Kaas procedure, a deprotection step, amide coupling, and hydrolysis were utilized as key chemical reactions towards the multistep synthesis of monomers in good to excellent isolated yields. The design strategy was further extended to complex carbazole-COOH monomers incorporated arylazo groups as photoreactive moieties. In addition, photoreactive hybrid carbazole (Cbz)-pyrrole (Pyr)-based carboxylated monomers, comprising a pyrrole core linking a carbazole and a photoreactive phenylazide or benzophenone moiety through an amide spacer in the molecular structure, were also synthesized. The latter can be utilized for surface modification of polymeric films in their monomeric form or as polymeric microparticles (MPs).

Targeted delivery of silver nanoparticles and alisertib: in vitro and in vivo synergistic effect against glioblastoma.

AIM: Targeted biocompatible nanoplatforms presenting multiple therapeutic functions have great potential for the treatment of cancer. MATERIALS & METHODS: Multifunctional nanocomposites formed by polymeric nanoparticles (PNPs) containing two cytotoxic agents - the drug alisertib and silver nanoparticles - were synthesized. These PNPs have been conjugated with a chlorotoxin, an active targeting 36-amino acid-long peptide that specifically binds to MMP-2, a receptor overexpressed by brain cancer cells. RESULTS: The individual and synergistic activity of these two cytotoxic agents against glioblastoma multiforme was tested both in vitro and in vivo. The induced cytotoxicity in a human glioblastoma-astrocytoma epithelial-like cell line (U87MG) was studied in vitro through a trypan blue exclusion test after 48 and 72 h of exposure. Subsequently, the PNPs' biodistribution in healthy animals and their effect on tumor reduction in tumor-bearing mice were studied using PNPs radiolabeled with (99m)Tc. CONCLUSION: Tumor reduction was achieved in vivo when using silver/alisertib@PNPs-chlorotoxin.

Biocompatible nanocomposite for PET/MRI hybrid imaging.

A novel nanocarrier system was designed and developed with key components uniquely structured at the nanoscale for early cancer diagnosis and treatment. In order to perform magnetic resonance imaging, hydrophilic superparamagnetic maghemite nanoparticles (NPs) were synthesized and coated with a lipophilic organic ligand. Next, they were entrapped into polymeric NPs made of biodegradable poly(lactic-co-glycolic acid) linked to polyethylene glycol. In addition, resulting NPs have been conjugated on their surface with a 2,2'-(7-(4-((2-aminoethyl)amino)-1-carboxy-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid ligand for subsequent (68)Ga incorporation. A cell-based cytotoxicity assay has been employed to verify the in vitro cell viability of human pancreatic cancer cells exposed to this nanosystem. Finally, in vivo positron emission tomography-computerized tomography biodistribution studies in healthy animals were performed.