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Functional Peptide Nanofibers with Unique Tumor Targeting and Enzyme‐Induced Local Retention Properties

Vanessa Bellat,Richard Ting,T. Southard,L. Vahdat,H. Molina,Joseph P. Fernandez,O. Aras,T. Stokol,Benedict Law

Published 2018 in Advanced Functional Materials

ABSTRACT

An effective tumoral delivery system should show minimal removal by the reticuloendothelial system (RES), promote tumor uptake and penetration, and minimize on‐site clearance. This study reports the design and synthesis of advanced self‐assembling peptide nanofiber precursor (NFP) analogues. The peptidic nature of NFP offers the design flexibility for on‐demand customization with imaging agents and surface charges while maintaining a set size, allowing for real‐time monitoring of kinetic and dynamic tumoral delivery by multimodal fluorescence/positron emission tomography/computed tomography (fluo/PET/CT) imaging, for formulation optimization. The optimized glutathione (GSH)‐NFP displays a reduced capture by the RES as well as excellent tumor targeting and tissue invasion properties compared to naïve NFP. Inside a tumor, GSH‐NFP can structurally transform into ten times larger interfibril networks, serving as in situ depot that promotes weeks‐long local retention. This nanofiber, which can further be designed to release the active pharmacophores within a tumor microenvironment, displays a superior therapeutic efficacy for inhibiting disease progression and improving the survival of animals bearing triple‐negative breast cancer tumors compared to free drug and liposome formulation of the drug, in addition to a favorable toxicity profile.

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