Peptide Amphiphile–Nanoparticle Assemblies for Mechano-Chemo Combination Therapy

Mechanical tumor ablation using focused ultrasound (FUS) offers minimally invasive ablation of solid tumors. However, mechanical tumor ablation requires highly intense FUS pulses, which may generate off-target effects. In addition, residual cancer cells that survive ablation can cause recurrence. To overcome these challenges, we developed a dual-functional nanomaterial by assembling peptide amphiphiles on hydrophobically modified nanoparticles. The hydrophobic nanoparticle core allows for the generation of cavitating bubbles at low FUS intensities to effectively ablate tumors. Peptide amphiphile shells interact dynamically with the hydrophobic nanoparticle surfaces and cell membranes, which improved tumor retention and cellular internalization of payloads attached to them. By conjugating a highly potent agent, Monomethyl auristatin E, to the peptide amphiphiles, we showed synergistic mechano- and chemotherapy using <i>in vitro</i> and <i>in vivo</i> models of human melanoma. This work presents a new nanoparticle approach to improving the outcomes of mechanical tumor ablation.