title: On-demand intracellular amplification of chemoradiation with cancer-specific plasmonic nanobubbles.
abstract: 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.
authors.affiliation: Department of Biochemistry and Cell Biology, Rice University, Houston, Texas, USA.
authors.forename: Ekaterina Y
authors.initials: EY
authors.lastname: Lukianova-Hleb
authors.affiliation: Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Ren
authors.affiliation: Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, Massachusetts, USA.
authors.forename: Rupa R
authors.initials: RR
authors.lastname: Sawant
authors.affiliation: Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Wu
authors.affiliation: Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, Massachusetts, USA.
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Torchilin
authors.affiliation: Department of Biochemistry and Cell Biology, Rice University, Houston, Texas, USA.|Department of Physics and Astronomy, Rice University, Houston, Texas, USA.
authors.forename: Dmitri O
authors.initials: DO
authors.lastname: Lapotko
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D051379:Mice; D049329:Nanostructures; D016896:Treatment Outcome