Journal
NATURE MEDICINE
Volume 20, Issue 7, Pages 778-784Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.3484
Keywords
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Funding
- US National Institutes of Health (NIH) [R0IGM094816]
- US National Science Foundation [CBET-1341212]
- Virginia and L.E. Simmons Family Foundation Award
- US NIH [R01CAl28486, 5U54151881-012, S10RR026399-01]
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [1341212] Funding Source: National Science Foundation
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Chemoradiation-resistant cancers limit treatment efficacy and safety. We show here the cancer cell-specific, on-demand intracellular amplification of chemotherapy and chemoradiation therapy via gold nanoparticle- and laser pulse-induced mechanical intracellular impact. Cancer aggressiveness promotes the clustering of drug nanocarriers and gold nanoparticles in cancer cells. This cluster, upon exposure to a laser pulse, generates a plasmonic nanobubble, the mechanical explosion that destroys the host cancer cell or ejects the drug into its cytoplasm by disrupting the liposome and endosome. The same cluster locally amplifies external X-rays. Intracellular synergy of the mechanical impact of plasmonic nanobubble, ejected drug and amplified X-rays improves the efficacy of standard chemoradiation in resistant and aggressive head and neck cancer by 100-fold in vitro and 17-fold in vivo, reduces the effective entry doses of drugs and X-rays to 2-6% of their clinical doses and efficiently spares normal cells. The developed quadrapeutics technology combines four clinically validated components and transforms a standard macrotherapy into an intracellular on-demand theranostic microtreatment with radically amplified therapeutic efficacy and specificity.
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