Biotin functionalized PEGylated poly(amidoamine) dendrimer conjugate for active targeting of paclitaxel in cancer

Abstract

In the current study, we employed poly(amidoamine) (PAMAM) dendrimers of generation 4 (G4) to deliver paclitaxel (PTX), a poorly soluble anti-cancer agent precisely to cancer cells via its conjugation on dendrimer surface. Further, G4 PAMAM has been PEGylated (PEG) and tagged with Biotin, an essential micronutrient for cellular functions, receptors of which are overexpressed in certain cancers. The synthesized multifunctional conjugates were characterized by 1H NMR and zeta potential analysis techniques. In addition, the conjugates were evaluated in vitro in cell monolayers and 3D spheroids of biotin receptor over-expressed A549 cell line (human non-small cell lung cancer). G4 PTX PEG-Biotin conjugate penetrated at significantly higher extent in monolayers as well as spheroids as studied by flow cytometry and confocal microscopy by visualizing the cells at varied depth. The G4 PTX PEG-Biotin conjugate demonstrated higher cytotoxicity compared to free PTX and G4 PTX PEG conjugate as assessed by MTT assay in monolayers and Presto Blue assay in detached spheroidal cells. G4 PTX PEG-Biotin demonstrated significant inhibition of growth of tumor spheroids. Therefore, the newly synthesized biotin anchored PTX-conjugated dendrimer system is promising and could be further explored for efficiently delivering PTX to biotin receptor overexpressed cancers.