Sulfonated gallium(III) corroles are intensely fluorescent macrocyclic compounds that spontaneously assemble with carrier proteins to undergo cell entry. We report in vivo imaging and therapeutic efficacy of a tumor-targeted corrole noncovalently assembled with a heregulin-modified protein directed at the human epidermal growth factor receptor (HER). Systemic delivery of this proteincorrole complex results in tumor accumulation, which can be visualized in vivo owing to intensely red corrole fluorescence. Targeted delivery in vivo leads to tumor cell death while normal tissue is spared. These findings contrast with the effects of doxorubicin, which can elicit cardiac damage during therapy and required direct intratumoral injection to yield similar levels of tumor shrinkage compared with the systemically delivered corrole. The targeted complex ablated tumors at >5 times a lower dose than untargeted systemic doxorubicin, and the corrole did not damage heart tissue. Complexes remained intact in serum and the carrier protein elicited no detectable immunogenicity. The sulfonated gallium(III) corrole functions both for tumor detection and intervention with safety and targeting advantages over standard chemotherapeutic agents.heregulin ͉ human epidermal growth factor receptor ͉ cancer ͉ in vivo imaging ͉ porphyrinoids

Corroles are exceptionally promising platforms for the development of agents for simultaneous cancer-targeting imaging and therapy. Depending on the element chelated by the corrole, these theranostic agents may be tuned primarily for diagnostic or therapeutic function. Versatile synthetic methodologies allow for the preparation of amphipolar derivatives, which form stable noncovalent conjugates with targeting biomolecules. These conjugates can be engineered for imaging and targeting as well as therapeutic function within one theranostic assembly. In this review, we begin with a brief outline of corrole chemistry that has been uniquely useful in designing corrole-based anticancer agents. Then we turn attention to the early literature regarding corrole anticancer activity, which commenced one year after the first scalable synthesis was reported (1999-2000). In 2001, a major advance was made with the introduction of negatively charged corroles, as these molecules, being amphipolar, form stable conjugates with many proteins. More recently, both cellular uptake and intracellular trafficking of metallocorroles have been documented in experimental investigations employing advanced optical spectroscopic as well as magnetic resonance imaging techniques. Key results from work on both cellular and animal models are reviewed, with emphasis on those that have shed new light on the mechanisms associated with anticancer activity. In closing, we predict a very bright future for corrole anticancer research, as it is experiencing exponential growth, taking full advantage of recently developed imaging and therapeutic modalities.

HerGa is a self-assembled tumor-targeted particle that bears both tumor detection and elimination activities in a single, two-component complex (Agadjanian et al., 2009, PNAS 106:6105–6110). Given its multifunctionality, HerGa (comprised of the fluorescent cytotoxic corrole macrocycle, S2Ga, noncovalently bound to the tumor-targeted cell penetration protein, HerPBK10) has the potential for high clinical impact, but its mechanism of cell killing remains to be elucidated, and hence is the focus of the present study. Here we show that HerGa requires HerPBK10-mediated cell entry to induce toxicity. HerGa (but not HerPBK10 or S2Ga alone) induced mitochondria membrane potential disruption and superoxide elevation, which were both prevented by endosomolytic-deficient mutants, indicating that cytosolic exposure is necessary for corrole-mediated cell death. A novel property discovered here is that corrole fluorescence lifetime acts as a pH indicator, broadcasting the intracellular microenvironmental pH during uptake in live cells. This feature in combination with two-photon imaging shows that HerGa undergoes early endosome escape during uptake, avoiding compartments of pH<6.5. Cytoskeletal disruption accompanied HerGa-mediated mitochondrial changes whereas oxygen scavenging reduced both events. Taxol-treatment indicated that HerGa uptake requires dynamic microtubules. Unexpectedly, low pH is insufficient to induce release of the corrole from HerPBK10. Altogether, these studies identify a mechanistic pathway in which early endosomal escape enables HerGa-induced superoxide generation leading to cytoskeletal and mitochondrial damage, thus triggering downstream cell death.

Wide range of color change in nanohole array structure on a metal film have been successfully demonstrated using asymmetric-lattice design of nanoholes and an electrically switching polarization rotator. Recently, some studies have been reported that various color states were obtained in a single unit cell structure using extraordinary optical transmission (EOT) of nanopatterned structure, which could be one of the most important solutions for achieving ultrahigh integration density in optoelectronic devices. However, because they used the interfacial refractive index or dielectric constant as controlling factors for the color tuning, they were not capable of inducing a changeable range of color with different primary color states. To overcome this limitation, in this study, an asymmetric-lattice nanohole array design was integrated with an electrically controlled polarization rotator, employing a twisted nematic (TN) liquid crystal (LC). This simple structure of nanohole arrays with a rectangular lattice enabled mixed color states as well as precisely designed two different primary colors, by modulating the polarization of the incident light. The color-tuning shift was greater than 120 nm. Since the surface plasmonic (SP) modes on both sides, a top and a bottom interface, were matched better by the TN-LC layer assembled on the rectangular-lattice nanohole metal layer, the transmittance at the resonance peak wavelength was increased by 158% compared to that of the bare nanohole structure. The nanohole-array-on-metal-film simultaneously functions as an electrode, and this advantage, coupled with the low driving voltage of the TN-LC layer, can open new possibilities in applications to various optoelectronic device concepts.

We investigate the potential of mobile smartphone-based multispectral imaging for the quantitative diagnosis and management of skin lesions. Recently, various mobile devices such as a smartphone have emerged as healthcare tools. They have been applied for the early diagnosis of nonmalignant and malignant skin diseases. Particularly, when they are combined with an advanced optical imaging technique such as multispectral imaging and analysis, it would be beneficial for the early diagnosis of such skin diseases and for further quantitative prognosis monitoring after treatment at home. Thus, we demonstrate here the development of a smartphone-based multispectral imaging system with high portability and its potential for mobile skin diagnosis. The results suggest that smartphone-based multispectral imaging and analysis has great potential as a healthcare tool for quantitative mobile skin diagnosis.