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 naive 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.

Self-assembly of mitochondria-specific peptide amphiphiles amplifying lung cancer cell death through targeting the VDAC1–hexokinase-II complex

“…[55][56][57] Lipopeptides containing a sequence of positively-charged aminoacid residues and an anchored fatty acid tail tend to self-assemble into a variety of nanostructures such as nanotubes, nanorods, nanofibrils, nanotapes, nanospheres, etc. [58][59][60][61][62] Modifying the amino-acid sequence and extending the hydrogen bonding, hydrophobic, electrostatic, π-π interactions, and van der Waals interactions can affect the shapes of the formed nano-assemblies, [63][64][65] their tendency to form three-dimensional networks, and their interactions with the biological membranes. 66,67 Studies have indicated that the self-assembly state (monomer, dimer, oligomer…) and the nanoarchitecture type may influence the biological outcome of the peptide amphiphiles in in vitro and in vivo applications.…”

Transcriptomic insight into salinomycin mechanisms in breast cancer cell lines: synergistic effects with dasatinib and induction of estrogen receptor β

“…In fact, the optimal drug ratio offering the strongest synergistic effect on the spheroids was 1:30. Further studies are required to investigate whether the observed discrepancies originated from differences in spheroidal penetration, and thus cellular uptakes, of the 2 drugs [40,41]. Overall, we demonstrated that our drug combination synergism was volatile, and strongly relied on the applied drug ratio as well as the employed cell culture and tumor spheroid models.…”

Peptide-Based Nanoassemblies in Gene Therapy and Diagnosis: Paving the Way for Clinical Application

“…These results suggest that peptidic nanofibers through noncovalent strategies have a remarkable potential for DNA delivery. Obviously, PNFs lend themselves to theranostic applications and have been widely employed as advanced materials for imaging [78]. Accordingly, gold nanoclusters (AuNCs) were introduced into self-assembled PNFs to enhance their luminescence efficiency.…”