Theranostic Poly Propyleneimine Dendrimers for Bioimaging and targeted delivery of anticancer drug for the treatment of Glioblastoma Multiforme

Abstract

The objective of the present study was development of theranostic poly propyleneimine newlinedendrimers for bioimaging and targeted delivery of anticancer drug for the treatment of newlineglioblastoma multiforme. Temozolomide and sliver sulphide QDs loaded angiopep-2 newlineconjugated PEGylated PPI dendrimers were prepared and characterized for various newlineparameters like spectroscopy techniques, particle size, surface morphology, loading newlineefficiency, in-vitro drug release, GBM cell line studies and in vivo animal studies. 4.0G PPI newlinedendrimers were synthesized using a divergent method. PEGylation PPI dendrimers was newlinedone with PEG3400. PEG-PPI was employed as a template to create Ag2S QDs in situ in newlineits nanocavities. ANG-2 was conjugated over the surface of dendrimers for brain and GBM newlinetargeting. Temozolomide drug was encapsulated in the carrier. Prepared theranostic carrier newlinewas characterized for size, shape, UV, FTIR, and drug loading, in vitro drug release and newlinestability studies. In vitro cell line studies were performed on both BCECs and C6 glioma newlinecells to evaluate the efficacy of theranostic carrier to target and treat GBM. The antitumor newlineactivity of TMZ loaded ANG-PEG-PPI Ag2S formulation against glioma was evaluated on newlineC6 glioma cells bearing mice. Synthesis of theranostic formulation was confirmed by newlineFTIR, NMR and Mass spectroscopy. TMZ loading was found to be 56.32±2.8%. In vitro newlinedrug release was found to be 52.86±2.09% in 24 hrs. No hemolytic toxicity was observed newlinefor the prepared formulation. Theranostic dendrimer formulations was found to be stable in newlinethe dark conditions and at lower temperatures. Theranostic dendrimer formulation shown newlinegood targeting and cytotoxicity against BCECs and C6 glioma cells. In vivo animal studies newlineon theranostic dendrimer formulation confirmed its accumulation at glioma site and good newlineantitumor activity. It can be concluded that prepared theranostic dendrimer formulation can newlinebe successfully used for simultaneous delivery of TMZ to brain glioma and real time newlinevisualization of the disease status. newline