Cell Environment-Differentiated Self-Assembly of Nanofibers

Abstract

Employing cellular environment for the self-assembly of supramolecular nanofibers for biological applications has been widely explored. But using one precursor to differentiate the extra- and intracellular environments to self-assemble into two different nanofibers remains challenging. With the knowledge that the extracellualr environment of some cancer cells contains large amounts of alkaline phosphatase (ALP) while their intracellular environment is glutathione (GSH)-abundant in mind, we rationally designed a precursor Cys(SEt)-Glu-Tyr(H2PO3)-Phe-Phe-Gly-CBT (1) that can efficiently yield amphiphilic 2 and 2-D to self-assemble into two different nanofibers in hydrogels under the sequential treatment of ALP and GSH. We envision that, by employing a click condensation reaction, this work offers a platform for facilely postmodulation of supramolecular nanofibers, and the versatile precursor 1 could be used to kill two birds with one stone.

Mitochondria localization induced self-assembly of peptide amphiphiles for cellular dysfunction

“…However, chemical and physical stimuli (e.g., light, temperature, pH, and redox) are not relevant for intracellular assembly because they induce severe damage to cell. Recently, enzyme instructed intracellular self-assembly (EISA) has emerged as an effective approach to induce cellular dysfunction, in which an enzyme changes the molecular structure of precursor from soluble hydrophilic to self-assembling units to form ordered-structure within the cell or pericellular space 8, 9 . However, EISA could not be generalized to various cancer cells, since the usage of biological stimuli (e.g., enzymes) is usually limited to specific cell types or cellular compartments.…”

Enzyme-Instructed Assembly and Disassembly Processes for Targeting Downregulation in Cancer Cells

“…Interestingly, although the mRNA expression of ALPL in OVSAHO cells is slightly higher than that in HepG2 cells, the two cell lines exhibit comparable phosphatase activities toward the precursors, which underscores the need to validate the enzyme activities experimentally for precise targeting of cancer cells. Although this work used ALP and CES, the principle demonstrated here should be applicable to any other enzymes 27 or cellular difference, 28 especially the difference in loss of functions, for spatiotemporal control of molecular assemblies that control cell fate.…”

Furin‐Controlled Fe3O4 Nanoparticle Aggregation and 19F Signal “Turn‐On” for Precise MR Imaging of Tumors

“…By taking advantage of the click condensation reaction reported by Rao and co-workers, [27][28][29] as displayed in Figure 1a, we first devised a small molecule 1 that can be cleaved by furin and spontaneously undergo click condensation reaction. A scrambled control compound TFMB-Arg-Lys-Arg-Cys(StBu)-Arg-Val-CBT (1-Scr) was employed for parallel study as it cannot be cleaved by furin.…”

“…2019,29, 1903860 The corresponding T 2 relaxation times were obtained (Figures S21b and S22b, Supporting Information) and the results are shown in Figure 2f and Figure S22c in the Supporting Information.…”