Markedly Enhanced Permeability and Retention Effects Induced by Photo-immunotherapy of Tumors

Abstract

A major barrier to cancer treatment is the inability to deliver sufficient concentrations of drug to the tumor without incurring systemic toxicities. Nanomaterials are appealing because they can carry a large drug payload; however, tumor delivery is limited by modest leakage and retention in most tumors. We observed that after photoimmunotherapy (PIT), which is a light-mediated treatment based on an antibody–photosensitizer conjugate, there was surprisingly high leakage of nanosized (10–200 nm) agents into the tumor bed. PIT rapidly induced death in perivascular cancer cells, leading to immediate and dramatic increases in vascular permeability, resulting in up to 24-fold greater accumulation of nanomaterials within the PIT-treated tumor compared with controls, an effect termed “super-enhanced permeability and retention”. In a treatment study, PIT followed by liposome-containing daunorubicin, DaunoXome (diameter 50 nm), resulted in greater survival in tumor-bearing mice than either PIT or DaunoXome alone. Thus, PIT greatly enhances delivery of nanosized reagents and thus holds promise to improve therapeutic responses