title: Photoswitchable nanoparticles for in vivo cancer chemotherapy.
abstract: There are many obstacles to effective cancer chemotherapy, including drug penetration and accumulation in tumors and drug systemic toxicity. The penetration of therapies into tumors is limited by the dense tumor matrix and by compression of the tumor vasculature. We have developed spiropyran-based nanoparticles that shrink from 103 to 49 nm upon irradiation at 365 nm. That shrinkage enhanced tissue penetration and drug release. Irradiation of s.c. HT-1080 tumors in nude mice administered i.v. docetaxel-containing nanoparticles was more effective treatment than free docetaxel or encapsulated docetaxel without irradiation. Irradiation at the tumor site also resulted in less systemic toxicity than if the nanoparticles were irradiated before injection, presumably because of less systemically distributed free drug. The enhanced efficacy of nanoparticles in irradiated tumors may have been related to the observed enhanced tumor penetration by nanoparticles and decompression of tumor blood vessels, which may also increase nanoparticle delivery into tumors.
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.
authors.forename: Rong
authors.initials: R
authors.lastname: Tong
authors.forename: Homer H
authors.initials: HH
authors.lastname: Chiang
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Kohane
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D001578:Benzopyrans; D016503:Drug Delivery Systems / Q000379:methods*; D006367:HeLa Cells; D006801:Humans; D007211:Indoles; D053758:Nanoparticles / Q000737:chemistry / Q000528:radiation effects*; D009369:Neoplasms / Q000188:drug therapy*; D009574:Nitro Compounds; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors; D014466:Ultraviolet Rays
chemical_list: D000970:Antineoplastic Agents; D001578:Benzopyrans; D007211:Indoles; D009574:Nitro Compounds; D013778:Tetrazolium Salts; D013844:Thiazoles; C088184:spiropyran; C022616:thiazolyl blue
keywords: nanomedicine; photoswitching; triggered drug delivery