Femtosecond Plasmonic Laser Nanosurgery (fs-PLN) mediated by molecularly targeted gold nanospheres at ultra-low pulse fluences.

Plasmonic Laser Nanosurgery (PLN) is a novel photomodification technique that exploits the near-field enhancement of femtosecond (fs) laser pulses in the vicinity of gold nanoparticles. While prior studies have shown the advantages of fs-PLN to modify cells, further reduction in the pulse fluence needed to initiate photomodification is crucial to facilitate deep-tissue treatments. This work presents an in-depth study of fs-PLN at ultra-low pulse fluences using 47 nm gold nanoparticles, conjugated to antibodies that target the epithelial growth factor receptor and excited off-resonance using 760 nm, 270 fs laser pulses at 80 MHz repetition rate. We find that fs-PLN can optoporate cellular membranes with pulse fluences as low as 1.3 mJ/cm2, up to two orders of magnitude lower than those used at lower repetition rates. Our results, corroborated by simulations of free-electron generation by particle photoemission and photoionization of the surrounding water, shed light on the off-resonance fs-PLN mechanism. We suggest that photo-chemical pathways likely drive cellular optoporation and cell damage at these off-resonance, low fluence, and high repetition rate fs-laser pulses, with clusters acting as local concentrators of ROS generation. We believe that the low fluence and highly localized ROS-mediated fs-PLN approach will enable targeted therapeutics and cancer treatment.

Mapping of vascular endothelium in the human flexor digitorum profundus tendon.

PURPOSE: Previous techniques to delineate the human flexor digitorum profundus (FDP) vasculature have been innovative but potentially imprecise, resulting in uncertainty as to the existence of avascular zones in the flexor tendon. We aimed to use a novel immunohistochemical technique to determine more accurately the vasculature of the human flexor tendon. METHODS: Thirty fresh cadaveric human FDP tendons were harvested, fixed, wax embedded, sectioned, and stained using the anti-CD31 monoclonal antibody to allow vessel visualization. Vessel numbers and vascularity density ratios were determined by computed image analysis. RESULTS: Vessel density ratios varied with anatomic location, with a decrease between the A2 and A4 pulleys. There also was variation in vascularity ratios in the anteroposterior plane, with the palmar surface of the tendons having a lower vessel density. CONCLUSIONS: We have shown that although areas of low vascularity exist on the palmar aspect of the tendon, there are no truly avascular zones.