Nanoparticle-based drug delivery systems (DDS) have been developed as effective diagnostic and low-dose imaging agents. Nano-imaging agents with particles greater than 100 nm are difficult to accumulate in pancreatic cancer cells, making high-intensity imaging of pancreatic cancer challenging. Peptides composed of histidine and glycine were designed and synthesized. Additionally, aqueous peptide solutions were irradiated with γ-rays to produce peptide nanogels with an average size of 25–53 nm. The mechanisms underlying radiation-mediated peptide crosslinking were investigated by simulating peptide particle formation based on rate constants. The rate constants for reactions between peptides and reactive species produced by water radiolysis were measured using pulse radiolysis. HGGGHGGGH (H9, H—histidine; G—glycine) particles exhibited a smaller size, as well as high formation yield, stability, and biodegradability. These particles were labeled with fluorescent dye to change their negative surface potential and enhance their accumulation in pancreatic cancer cells. Fluorescent-labeled H9 particles accumulated in PANC1 human pancreatic cancer cells, demonstrating that these particles are effective nano-imaging agents for intractable cancers.
Nanoparticles have been employed to develop nanosensors and drug carriers that accumulate in tumors. Thus, it is necessary to control the particle size, surface potential, and biodegradability of these nanoparticles for effective tumor accumulation and safe medical application. In this study, to form a nanoparticle platform suitable for diagnostic and drug delivery system (DDS) applications, peptides composed of aromatic amino acid residues were designed and synthesized based on the radiation crosslinking mechanism of proteins. The peptide nanoparticles, which were produced by γ-ray irradiation, displayed a positive surface potential, maintained biodegradability, and were stable in water and phosphoric buffer solution during actual diagnosis. The surface potential of the peptide nanoparticles could be changed to negative by using a fluorescent labeling reagent, so that the fluorescent-labeled peptide nanoparticles were uptaken by HeLa cells. The radiation-crosslinked nanoparticles can be applied as a platform for tumor-targeting diagnostics and DDS therapy.
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