In recent years, much research has focused on assemblies formed by charged
polyelectrolytes via electrostatic interactions in aqueous solutions as they have the potential to be used in a variety of biomedical applications. In this study, we analyzed supramolecular architectures fabricated from poly(N-allyl
glycine) modified with
cysteamine (PNAG-NH2) and
folic acid (FA) via electrostatic interactions. The PNAG-NH2/FA complex exhibits a reversible pH-responsive morphological transformation from vesicles (pH = 7.0) to nanofibers (pH = 5.0). Besides, we demonstrated that homopolypeptoids electrostatically interact with FA, thereby facilitating ribbon- and disk-like H-bonded FA patterns and inducing the formation of vesicle nanostructures and fiber arrays, respectively. Additionally, we systematically studied the influence of the degree of polymerization of the
polymers, concentration, charge mixing ratio, and type of the
polymer and the small-molecule
acid on the assemblies. We show the superior stability of the polypeptoid/FA complex as compared to those based on other
polymers. We established that the polypeptoid/FA complex exhibits a superior stability than those based on other
polymers. By applying these beneficial properties, we encapsulated the anticancer drug
doxorubicin (DOX) in the complex vesicle to obtain a pH-induced
drug carrier. Cytotoxicity studies and internalization assays revealed that the DOX-loaded PNAG-NH2/FA complex vesicles display an enhanced therapeutic efficacy via typical FA-
folate receptor-mediated endocytosis in vitro.