A crosslinked colloidal network of peptide/nucleic base amphiphiles for targeted cancer cell encapsulation

Abstract

The use of peptide amphiphiles (PAs) is becoming increasingly popular, not only because of their unique self-assembly properties but also due to the versatility of designs, allowing biological responsiveness, biocompatibility, and easy synthesis, which could potentially contribute to new drug design and disease treatment concepts. Oligonucleotides, another major functional bio-macromolecule class, have been introduced recently as new functional building blocks into PAs, further enriching the tools available for the fabrication of bio-functional PAs. Taking advantage of this, in the present work, two nucleic base-linked (adenine, A and thymine, T) RGD-rich peptide amphiphiles (NPAs) containing the fluorophores naphthalimide and rhodamine (Nph-AandRh-T) were designed and synthesized. The two NPAs exhibit distinctive assembly behaviours with spherical (Rh-T) and fibrous (Nph-A) morphologies, and mixingNph-AwithRh-Tleads to a densely crosslinked colloidal network (Nph-A/Rh-T)viamutually promoted supramolecular polymerizationvianucleation-growth assembly. Because of the RGD-rich sequences in the crosslinked network, further research onin situtargeted cancer cell (MDA-MB-231) encapsulationviaRGD-integrin recognition was performed, and the modulation of cell behaviours (e.g., cell viability and migration) was demonstrated using both confocal laser scanning microscopy (CLSM) imaging and a scratch wound healing assay.