title: Safety and efficacy of quadrapeutics versus chemoradiation in head and neck carcinoma xenograft model.
abstract: Chemoradiation is the strongest anti-tumor therapy but in resistant unresectable cancers it often lacks safety and efficacy. We compared our recently developed cell-level combination approach, quadrapeutics, to chemoradiation therapy to establish pre-clinical data for its biodistribution, safety and efficacy in head and neck squamous cell carcinoma (HNSCC), as a clinically challenging aggressive and resistant cancer. In vitro and in vivo models of four carcinomas were treated with standard chemoradiation and quadrapeutics using identical drug and radiation doses. We applied liposomal cisplatin or doxorubicin, colloidal gold, near-infrared laser pulses and radiation, all at low safe doses. The final evaluation used a xenograft model of HNSCC. Quadrapeutics enhanced standard chemoradiation in vitro by reducing head and neck cancer cell proliferation by 1000-fold, inhibiting tumor growth in vivo by 34-fold and improving animal survival by 5-fold, and reducing the side effects to a negligible level. In quadrapeutics, we observed an "inversion" of the drug efficacy of two standard drugs: doxorubicin, a low efficacy drug for the cancers studied, was two times more efficient than cisplatin, the first choice drug in clinic for HNSCC. The radical therapeutic gain of quadrapeutics resulted from the intracellular synergy of the four components employed which we administered in a specific sequence, while the reduction in the toxicity was due to the low doses of all four components. The biodistribution, safety and efficacy data for quadrapeutics in HNSCC ensure its high translational potential and justify the possibility of clinical trials.
authors.affiliation: Department of BioSciences at Rice, Rice University Houston, TX 77005, USA.
authors.forename: Ekaterina Y
authors.initials: EY
authors.lastname: Lukianova-Hleb
authors.affiliation: Department of Translational Imaging, Houston Methodist Research Institute Houston, TX 77030, USA.
authors.forename: Yoo-Shin
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University Boston, MA 02115, USA.
authors.forename: Bhawani
authors.initials: B
authors.lastname: Aryasomayajula
authors.affiliation: Regulon Inc. Alimos 17455, Greece.
authors.forename: Teni
authors.initials: T
authors.lastname: Boulikas
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center Houston, TX 77030, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Phan
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer CenterHouston, Texas 77030, USA; Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical UniversityTaichung, Taiwan.
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
authors.affiliation: Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University Boston, MA 02115, USA.
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Torchilin
authors.affiliation: Department of Translational Imaging, Houston Methodist Research Institute Houston, TX 77030, USA.
authors.forename: Brian E
authors.initials: BE
authors.lastname: O'Neill
authors.affiliation: Department of BioSciences at Rice, Rice University Houston, TX 77005, USA.
authors.forename: Dmitri O
authors.initials: DO
authors.lastname: Lapotko
keywords: Carcinoma; chemoradiation; drug resistance; laser; nanomedicine; plasmonic nanobubble; quadrapeutics