Photoswitchable nanoparticles for in vivo cancer chemotherapy

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 n...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2013-11, Vol.110 (47), p.19048-19053
Main Authors: Tong, Rong, Chiang, Homer H., Kohane, Daniel S.
Format: Article
Language:English
Subjects:
Antineoplastic Agents - chemistry
Antineoplastics
Benzopyrans
Biological Sciences
Blood vessels
Cancer
Chemotherapy
Collagens
Dosage
Drug Delivery Systems - methods
Endothelial cells
Fluorescence
HeLa Cells
Humans
Imaging
Indoles
Irradiation
Nanoparticles
Nanoparticles - chemistry
Nanoparticles - radiation effects
Neoplasms - drug therapy
Nitro Compounds
Physical Sciences
Tetrazolium Salts
Thiazoles
Time Factors
Toxicity
Tumors
Ultraviolet Rays
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1315336110