title: 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.
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1088, USA.
authors.forename: Kohei
authors.initials: K
authors.lastname: Sano
authors.forename: Takahito
authors.initials: T
authors.lastname: Nakajima
authors.forename: Peter L
authors.initials: PL
authors.lastname: Choyke
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003630:Daunorubicin / Q000008:administration & dosage*; D005260:Female; D007167:Immunotherapy; D008027:Light; D051379:Mice; D008819:Mice, Nude; D053769:Nanocapsules / Q000627:therapeutic use*; D009374:Neoplasms, Experimental / Q000737:chemistry / Q000628:therapy*; D010539:Permeability / Q000187:drug effects; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D053769:Nanocapsules; D017319:Photosensitizing Agents; D003630:Daunorubicin