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Channel Rhodopsins

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pH-Responsive Rhodamine Nanotube Capable of Self-Reporting the Assembly State.

Ziyuan Meng¹, Sagarika Taneja¹, Reham Hassan¹

¹Department of Chemistry and Biochemistry, The Ohio State University, 100 W. 18th Avenue, Columbus, Ohio 43210, United States.

ACS Applied Materials & Interfaces

|August 28, 2024

Summary

Novel rhodamine-peptides form nanotubes at physiological pH and dissociate into fluorescent monomers in acidic cellular compartments, enabling targeted drug delivery. These pH-responsive nanomaterials show promise for biomedical applications.

Keywords:

live-cell imaging nanotubes pH-responsivity peptides self-assembly

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Area of Science:

Biomedical Engineering
Materials Science
Chemical Biology

Background:

Nanomaterials responding to intracellular signals like pH are crucial for targeted biomedical applications, including drug delivery.
Tailoring assembly/disassembly to specific subcellular pH environments enhances therapeutic efficacy.

Purpose of the Study:

To develop and characterize novel rhodamine-peptides that self-assemble into nanotubes at physiological pH and disassemble in acidic cellular compartments.
To investigate the pH-dependent behavior of these rhodamine-peptides for potential use in drug delivery systems.

Main Methods:

Synthesis and characterization of two rhodamine-peptide conjugates (RhB-KK and RhB-KE).
Utilized circular dichroism (CD), fluorescence spectroscopy, transmission electron microscopy (TEM), and atomic force microscopy (AFM) to study pH-dependent assembly.
Evaluated pH-responsive behavior and cellular uptake in cancer cell lines using confocal laser scanning microscopy (CLSM).

Main Results:

RhB-KK and RhB-KE nanotubes assemble above pH ~4-5 and dissociate into fluorescent monomers at lower pH.
The onset of assembly occurred at pH 4.6 for RhB-KE and pH 5.8 for RhB-KK.
Live-cell imaging demonstrated nanotube uptake and dissociation into monomers within acidic lysosomes, confirmed by colocalization studies.

Conclusions:

Developed pH-responsive rhodamine-peptides that exhibit controlled assembly and disassembly based on intracellular pH.
These nanomaterials successfully trafficked into lysosomes and dissociated, indicating potential for targeted intracellular drug delivery.
Cellular uptake mechanisms were identified as caveolae- or clathrin-mediated endocytosis, depending on the cell line.