Photoswitchable nanoparticles for in vivo cancer chemotherapy

Significance The importance of this research is in the demonstration of the effectiveness and improved safety of a nanoparticulate chemotherapeutic formulation that can be phototriggered to shrink in size at the tumor site. That shrinkage enhanced nanoparticle penetration into tumors and also triggered local drug release. The result was increased efficacy and reduced systemic toxicity. The phototriggered formulation also relieved the compression of tumor blood vessels, which is a recognized barrier to nanoparticle accumulation in tumors. 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.

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