Hyaluronic acid modification of RNase A and its intracellular delivery using lipid-like nanoparticles

Developing safe and effective nanosystems to deliver active and therapeutic proteins to targeted cells and organs is an important tool for many biomedical applications. We present here a simple and efficient strategy for this purpose: delivering hyaluronic acid (HA)-modified RNase A (RNase A-HA) in nanocomplex with cationic lipid-like molecules (lipidoids) to cancer cells, resulting in targeted inhibition of cancer proliferation. The chemical conjugation of RNase A with HA both increased the supramolecular interaction with carrier lipidoids, promoting protein encapsulation efficacy, and facilitated cancer cell targeting via interaction with overexpressed CD44. Through confocal laser scanning microscopy and flow cytometry analysis, we demonstrated that protein/lipidoid nanoparticles could facilely enter cells with high CD44 expression, and inhibit cell proliferation in a dose-dependent manner.