Förster resonance energy transfer (FRET) may be regarded as a “smart” technology in the design of fluorescence probes for biological sensing and imaging. Recently, a variety of nanoparticles that include quantum dots, gold nanoparticles, polymer, mesoporous silica nanoparticles and upconversion nanoparticles have been employed to modulate FRET. Researchers have developed a number of “visible” and “activatable” FRET probes sensitive to specific changes in the biological environment that are especially attractive from the biomedical point of view. This article reviews recent progress in bringing these nanoparticle-modulated energy transfer schemes to fruition for applications in biosensing, molecular imaging and drug delivery.

Photodynamic therapy (PDT), the use of light to excite photosensitive molecules whose electronic relaxation drives the production of highly cytotoxic reactive oxygen species (ROS), has proven an effective means of oncotherapy. However, its application has been severely constrained to superficial tissues and those readily accessed either endoscopically or laparoscopically, due to the intrinsic scattering and absorption of photons by intervening tissues. Recent advances in the design of nanoparticle-based X-ray scintillators and photosensitizers have enabled hybridization of these moieties into single nanocomposite particles. These nanoplatforms, when irradiated with diagnostic doses and energies of X-rays, produce large quantities of ROS and permit, for the first time, non-invasive deep tissue PDT of tumors with few of the therapeutic limitations or side effects of conventional PDT. In this review we examine the underlying principles and evolution of PDT: from its initial and still dominant use of light-activated, small molecule photosensitizers that passively accumulate in tumors, to its latest development of X-ray-activated, scintillator–photosensitizer hybrid nanoplatforms that actively target cancer biomarkers. Challenges and potential remedies for the clinical translation of these hybrid nanoplatforms and X-ray PDT are also presented.

Although valuable insights into colon cancer biology have been garnered from human colon cancer cell lines and primary colonic tissues, and animal studies using human colon cancer xenografts, immunocompetent mouse models of spontaneous or chemically induced colon cancer better phenocopy human disease. As most sporadic human colon tumors present adenomatous polyposis coli (APC) gene mutations, considerable effort has gone into developing mice that express mutant Apc alleles that mimic human colon cancer pathogenesis. A serious limitation of many of these Apc-mutant murine models, however, is that these mice develop numerous tumors in the small intestine but few, if any, in the colon. In this work, we examined three spontaneous mouse models of colon tumorigenesis based upon the widely used multiple intestinal neoplasia (Min) mouse: mice with either constitutive or conditional Apc mutations alone or in combination with caudal-related homeobox transcription factor CDX2P-Cre transgene — either with or without exposure to the potent colon carcinogen azoxymethane. Using the CDX2 promoter to drive Cre recombinase transgene expression effectively inactivated Apc in colonocytes, creating a model with earlier tumor onset and increased tumor incidence/burden, but without the Min mouse model’s small intestine tumorigenesis and susceptibility to intestinal perforation/ulceration/hemorrhage. Most significantly, azoxymethane-treated mice with conditional Apc expression, but absent the Cre recombinase gene, demonstrated nearly 50% tumor incidence with two or more large colon tumors per mouse of human-like histology, but no small intestine tumors — unlike the azoxymethane-resistant C57BL/6J-background Min mouse model. As such this model provides a robust platform for chemoprevention studies.

In fluorescence spectroscopy and imaging, fluorescence lifetime measurement—assessing the average time fluorophores spend in their excited state before returning to their ground state—offers a number of advantages over quantifying fluorescence intensities that include resistance to photo-bleaching and independence from fluorophore concentration, excitation intensity, and measurement methodology. Despite growing interest, fluorescence lifetime techniques frequently mandate relatively complex instrumentation, slow data acquisition rates, and significant data analyses. In this work, we demonstrate the feasibility of measuring fluorescence lifetimes using off-the-shelf analog silicon photomultipliers and switched-capacitor array waveform sampling techniques, with precision matching that of much larger and more elaborate commercial instruments.

Forms of sonodynamic therapy rely on close interactions between microbubbles and agents to generate cytotoxic reactive oxygen species. Microbubbles are inherently intravascular agents, which limits the therapeutic range for effective distribution of reactive oxygen species. Histotripsy is a focused ultrasound therapy that ablates tissue via the generation of a dense cloud of bubbles spontaneously without the need for microbubbles. This study investigated the capacity of histotripsy to generate the hydroxyl radical with and without sonodynamic agents. In the absence of sonodynamic agents, histotripsy produced the hydroxyl radical at rate that was increased by a factor of three relative to other forms of therapeutic ultrasound. These sonochemical reactions were found to correlate strongly with acoustic emissions tracked with passive cavitation imaging. Histotripsy bubble activity was found to increase the rate of hydroxyl radical production for multiple sonosensitizers relative to controls, particularly for ultrasound pulses longer than 20 cycles (i.e., 20 μs) in duration. Overall, these data indicate histotripsy may be a viable approach for activating sonosensitve agents, and this activation may be tracked based on acoustic emission.