Gold-nanorods incorporated with microbubbles (AuMBs) were introduced as a photoacoustic/ultrasound dual-
modality contrast agent in our previous study. The application can be extended to theragnosis purpose. With the unique physical characteristics of AuMBs, we propose an enhanced delivery method for the encapsulated particles. For example, laser thermotherapy mediated by plasmonic nanoparticles can be made more effective by using microbubbles as a
targeted carrier and acoustic cavitation for enhanced sonoporation. The hypothesis was experimentally tested. Firts, these
AuMBs first act as molecular probes with binding to specific ligands. The improved targeting efficacy was
macroscopically observed by an ultrasound system. The extended retention of targeted AuMB was observed and
recorded for 30 minutes in a CT-26 tumor bearing mouse. Secondly, cavitation induced by time-varying acoustic field
was also applied to disrupt the microbubbles and cause increased transient cellular permeability (a.k.a., sonoporation).
Multimodal optical microscope based on a Cr:forsterite laser was used to directly observe these effects. The microscope can acquired third-harmonic generation (THG) and two-photon fluorescent (2PF) signals produced by the AuMBs. In vitro examination shows approximately a 60% improvement in terms of fluorescence signals from the cellular uptake of gold nanoparticles after sonoporation treatment. Therefore, we conclude that the controlled release is feasible and can
further improve the therapeutic effects of the nanoparticles.
To investigate whether endogenous biliverdins can serve as a fluorescence metabolic marker in cancer diagnosis, we
measured their multiphoton fluorescence spectra and lifetimes with femtosecond Cr:forsterite laser. Excited at 1230nm,
the two-photon fluorescence of biliverdins peaks around 670nm. The corresponding lifetime (<100ps) was much shorter
than those of porphyrins (~10ns), which is another commonly present metabolites in living cells. Further mixing
biliverdins with proteins like fetal bovine serum (FBS), biliverdins reductase A (BVRA), or heme oxygenase-1 (HO-1),
the yields of red autofluorescences didn't change a lot, but the corresponding lifetimes with HO-1 and BSA were
lengthened to 200~300ps. This indicates that biliverdin can have an association with these proteins and change its
lifetime. These spectral and temporal characteristics of fluorescence make biliverdin a potential marker fluorophore for
hyperspectral diagnosis on the heme catabolism in human cells or tissues.