title: Intraoperative diagnostics and elimination of residual microtumours with plasmonic nanobubbles.
abstract: Failure of cancer surgery to intraoperatively detect and eliminate microscopic residual disease (MRD) causes lethal recurrence and metastases, and the removal of important normal tissues causes excessive morbidity. Here, we show that a plasmonic nanobubble (PNB), a non-stationary laser pulse-activated nanoevent, intraoperatively detects and eliminates MRD in the surgical bed. PNBs were generated in vivo in head and neck cancer cells by systemically targeting tumours with gold colloids and locally applying near-infrared, low-energy short laser pulses, and were simultaneously detected with an acoustic probe. In mouse models, between 3 and 30 residual cancer cells and MRD (undetectable with current methods) were non-invasively detected up to 4 mm deep in the surgical bed within 1 ms. In resectable MRD, PNB-guided surgery prevented local recurrence and delivered 100% tumour-free survival. In unresectable MRD, PNB nanosurgery improved survival twofold compared with standard surgery. Our results show that PNB-guided surgery and nanosurgery can rapidly and precisely detect and remove MRD in simple intraoperative procedures.
authors.affiliation: Department of BioSciences at Rice, Rice University, Houston, Texas 77005, USA.
authors.forename: Ekaterina Y
authors.initials: EY
authors.lastname: Lukianova-Hleb
authors.affiliation: Department of Translational Imaging, Methodist Hospital Research Institute, Houston, Texas 77030, USA.
authors.forename: Yoo-Shin
authors.initials: YS
authors.lastname: Kim
authors.affiliation: N.N. Alexandrov National Cancer Centre of Belarus, Minsk 223040, Belarus.
authors.forename: Ihor
authors.initials: I
authors.lastname: Belatsarkouski
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Gillenwater
authors.affiliation: Department of Translational Imaging, Methodist Hospital Research Institute, Houston, Texas 77030, USA.
authors.forename: Brian E
authors.initials: BE
authors.lastname: O'Neill
authors.affiliation: Department of BioSciences at Rice, Rice University, Houston, Texas 77005, USA.
authors.forename: Dmitri O
authors.initials: DO
authors.lastname: Lapotko
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006046:Gold / Q000627:therapeutic use; D006258:Head and Neck Neoplasms; D006801:Humans; D053685:Laser Therapy; D053768:Metal Nanoparticles / Q000627:therapeutic use; D051379:Mice; D045423:Microbubbles / Q000627:therapeutic use*; D049329:Nanostructures / Q000627:therapeutic use*; D018365:Neoplasm, Residual / Q000000981:diagnostic imaging / Q000628:therapy; D025321:Surgery, Computer-Assisted / Q000379:methods*; D000068936:Theranostic Nanomedicine / Q000379:methods*
chemical_list: D006046:Gold