Peptide-containing aggregates as selective nanocarriers for therapeutics

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Therapeutics

Background:

• Development of targeted drug delivery systems is crucial for improving cancer treatment efficacy and reducing side effects.
• Cholecystokinin receptors (CCKRs) are overexpressed in certain cancer types, presenting a potential target for therapeutic interventions.
• Amphiphilic monomers offer a versatile platform for constructing sophisticated nanocarrier architectures.

Purpose of the Study:

• To synthesize and characterize novel nanocarriers for targeted cancer therapy.
• To evaluate the targeting capability and drug delivery efficiency of these nanocarriers.
• To assess the in vitro efficacy of drug-loaded nanocarriers against CCKR-expressing cancer cells.

Main Methods:

• Synthesis of two amphiphilic monomers: (C18)2PEG2000CCK8 and (C18)2DTPAGlu.
• Structural characterization of nanocarrier aggregates using dynamic light scattering, small-angle neutron scattering, and cryogenic transmission electron microscopy.
• In vitro binding assays, in vivo biodistribution studies using indium-111, and cytotoxicity assays with doxorubicin.

Main Results:

• Formation of polydisperse aggregates including rod-like micelles, bilayer fragments, and vesicles at pH 7.4 and a 30:70 monomer ratio.
• Demonstrated selective targeting of nanocarriers to CCKRs due to exposed CCK8 peptide.
• In vitro and in vivo studies confirmed nanocarrier targeting and biodistribution.
• Drug-loaded nanocarriers showed significantly reduced survival in CCKR-positive cancer cells compared to controls.

Conclusions:

• Novel nanocarriers assembled from amphiphilic monomers show promise for targeted cancer therapy.
• The CCK8 peptide facilitates specific targeting of cancer cells overexpressing CCKRs.
• These nanocarriers demonstrate effective drug loading and enhanced cytotoxicity against target cancer cells.