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Continuous flow fabrication of Fmoc-cysteine based nanobowl infused core-shell like microstructures for pH switchable on-demand anti-cancer drug delivery.

Asymmetric nanostructures such as nanobowls (NBs) can exhibit superior drug delivery performances owing to their concave structure and interior asymmetric cavities. Here, we present a facile one-step method for the… Click to show full abstract

Asymmetric nanostructures such as nanobowls (NBs) can exhibit superior drug delivery performances owing to their concave structure and interior asymmetric cavities. Here, we present a facile one-step method for the fabrication of NB like structures from a mere single amino acid mimetic, N-(9-fluorenylmethoxycarbonyl)-S-triphenylmethyl-l-cysteine following continuous-flow microfluidics enabled supramolecular self-assembly. Following fabrication, NBs were further infused into a vesicular shell consisting of the amino acid N-(tert-butoxycarbonyl)-S-triphenylmethyl-l-cysteine, carrying dual acid labile groups, the triphenylmethyl and the tert-butyloxycarbonyl groups. The NB infused core-shell like microstructures formed after the shell coating will now be addressed as NB-shells. Presence of pH-responsive shells bestowed the core-shell NB like structures with the ability to actively tune their surface pore opening and closing in response to environmental pH switch. To illustrate the potential use of the NB-shells in the field of anticancer drug delivery, the particles were loaded with doxorubicin (Dox) with an encapsulation efficiency of 42% and Dox loaded NB-shells exhibited enhanced efficacy in C6 glioma cells. Additionally, when tested in an animal model of glioblastoma, the nanoformulations demonstrated significantly higher retardation of tumour growth as compared to free Dox. Thus, this work strives to provide a new research area in the development of well turned-out and neatly fabricated pH switchable on/off anti-cancer drug delivery systems with significant translational potential.

Keywords: shell; drug delivery; shell like; core shell

Journal Title: Biomaterials science
Year Published: 2021

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