Β-cyclodextrin based dual-responsive multifunctional nanotheranostics for cancer cell targeting and dual drug delivery. (15th February 2019)

• Record Type: Journal Article
• Authors: Das, Manita; Solanki, Archana; Joshi, Apeksha; Devkar, Ranjitsinh; Seshadri, Sriram; Thakore, Sonal
• Is Part Of: Carbohydrate polymers. Volume 206(2019)
• Page Start: 694
• Page End: 705
• Publication Date: 2019-02-15
• Subjects: β-cyclodextrin -- Multifunctional nanoconjugates -- Drug delivery -- Nanotheranostics -- Stimuli responsive -- Thermo-responsive; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2018.11.049
• Languages: English
• ISSNs: 0144-8617

Abstract

Graphical abstract: Highlights: Nanocarriers based on β-Cyclodextrin modified with Maleic anhydride and NIPAM for dual, pH and temperature responsive drug release are reported. Multiple functionalities conjugated to magnetic nanoparticle platform in two step one pot synthesis with urethane /urea linkages. Simultaneous loading and release of Doxorubicin and Curcumin. Endocytosis monitored by fluorescence. Targeted cancer cell death in vitro manifested by significant tumor regression in vivo . Abstract: Multifunctional nanoconjugates possessing an assortment of key functionalities such as magnetism, florescence, cell-targeting, pH and thermo-responsive features were developed for dual drug delivery. The novelty lies in careful conjugation of each of the functionality with magnetic Fe3 O4 nanoparticles by virtue of urethane linkages instead of silica in a simple one pot synthesis. Further β-cyclodextrin (CD) was utilized to carry hydrophobic as well as hydrophilic drug. Superlative release of DOX could be obtained under acidic pH conditions and elevated temperature, which coincides with the tumor microenvironment. Mathematical modelling studies revealed that the drug release kinetics followed diffusion mechanism for both hydrophobic drug and hydrophilic drug. A number of fluorophores onto a single nanoparticle produced a strong fluorescence signal to optically track the nanoconjugates. Enhanced internalization due to folate specificity could be observed by fluorescence imaging. Further their accumulation driven by magnet near tumor site led to magnetic hyperthermia. in vitro studies confirmed the nontoxicity and hemocompatibility of the nanoconjugates. Remarkable cell death was observed with drug-loaded nanoconjugates at very low concentrations in cancer cells. The internalization and cellular uptake of poor bioavailable anticancer agent curcumin were found to be remarkably enhanced on dosing the drug loaded nanoconjugates as compared to free curcumin. Site specific drug delivery due to folate conjugation and subsequent significant suppression in tumor growth was demonstrated by in vivo studies.