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

ACS Nano. 2013 Jan 22;7(1):717-24. doi: 10.1021/nn305011p. Epub 2012 Dec 18.

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Daunorubicin / administration & dosage*
  • Female
  • Immunotherapy
  • Light
  • Mice
  • Mice, Nude
  • Nanocapsules / therapeutic use*
  • Neoplasms, Experimental / chemistry
  • Neoplasms, Experimental / therapy*
  • Permeability / drug effects
  • Photochemotherapy / methods*
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / therapeutic use*
  • Treatment Outcome

Substances

  • Antibiotics, Antineoplastic
  • Nanocapsules
  • Photosensitizing Agents
  • Daunorubicin