Novel pyranopyridine derivatives and their radiolabeled nanoconjugates: An augmented approach for targeted cancer theranostics

Nanoconjugates represent a revolutionary approach in the realm of cancer management, merging therapeutic and diagnostic capabilities into a cohesive framework. Herein, the study aimed to synthesis a novel anticancer agent based pyranopyridine derivative and augment its theranostic potential as a radio-nanoconjugate. Novel series of pyranopyridine derivatives (6a-c) were synthesized and their structures were verified by different elemental techniques (FTIR, 1 H NMR and mass spectroscopy). The synthetic molecules demonstrated cytotoxicity against cancerous MCF-7 and A549 cells. Derivative 6a with indole moiety displayed the strongest anti-proliferative impact with an IC 50 of 1.9 and 2.7 μg mL −1, while derivatives 6b and 6c showed IC 50 of (3.9 and 6.47 μg mL −1 ) and (3.6 and 3.87 μg mL −1 ), respectively. The most potent synthesized compound (6a) was covalently conjugated to zinc oxide nanoparticles (ZnO@Glu) exploring a nanoconjugate (derivative 6a-conjugated ZnO@Glu) with 34 nm diameter, 45 nm hydrodynamic size and −18mV zeta potential. The prepared nanoconjugate displayed potential anti-proliferative impact against cancerous MCF-7 and A549 cells boasting ∼6 and 5.8 times lower IC 50, respectively, compared to derivative 6a. Then, derivative 6a and the nanoconjugate were radiolabeled with iodine-131 radionuclide [ 131 I] achieving >95 % radiolabeling efficiency. Upon evaluating [ 131 I]I-derivative 6a in-vivo in mice-harboring-tumors, the highest tumor accumulation was 2.4 %ID/g at 1h post iv-injection, accompanied by target/non-target ratio of 1.7. Conversely, the in-vivo assessment of [ 131 I]I-nanoconjugate revealed a maximal tumor accumulation of 11.5 %ID/g at 1h post iv-injection, accompanied by target/non-target ratio of 10.5. Herein, [ 131 I]I-derivative 6a-conjugated ZnO@Glu could be utilized as a tumor-targeted platform for cancer theranostics.