Functional peptide nanofibers with unique tumor targeting and enzyme-induced local retention properties Journal Article
| Authors: | Bellat, V.; Ting, R.; Southard, T. L.; Vahdat, L.; Molina, H.; Fernandez, J.; Aras, O.; Stokol, T.; Law, B. |
| Article Title: | Functional peptide nanofibers with unique tumor targeting and enzyme-induced local retention properties |
| 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. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim |
| Keywords: | doxorubicin; tomography; tumors; peptides; diseases; tumor microenvironment; triple negative breast cancer; targeted drug delivery; controlled drug delivery; triple-negative breast cancers; real time monitoring; nanofibers; interfibril network; peptide nanofibers; tumoral uptake and retention; formulation optimization; reticuloendothelial systems; self-assembling peptides |
| Journal Title: | Advanced Functional Materials |
| Volume: | 28 |
| Issue: | 44 |
| ISSN: | 1616-301X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2018-10-31 |
| Start Page: | 1803969 |
| Language: | English |
| DOI: | 10.1002/adfm.201803969 |
| PROVIDER: | scopus |
| PMCID: | PMC6261308 |
| PUBMED: | 30505260 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 December 2018 -- Source: Scopus |
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