Water-soluble benzophenoxazine dyes: syntheses, derivatization and photophysical studies

A set of three benzophenoxazine dyes, two completely soluble and one partially soluble in aqueous media, has been prepared and their spectroscopic properties examined. These dyes can be used as either donor or acceptor in synthesis of through-bond energy transfer cassettes. Structural modifications prevented aggregation in water and improved their fluorescence properties in water. Their absorption and emission were studied in both organic and aqueous media. Two of the three dyes have superior quantum yields in aqueous media as compared to other reported dyes. Improved quantum yield makes these dyes attractive candidates for biological studies in aqueous media. We have also prepared alkynes and iodo derivatives of benzophenoxazines, which can be used for synthesis of water-soluble, through-bond, energy transfer cassettes. Alkynes were prepared via Sonogashira coupling

Synthesis of Through-bond Energy Transfer Cassettes and Their Encapsulation in Silica and Calcium Phosphate Nanoparticles

Water-soluble fluorescent probes with emission in the 600-800 nm region have significant potential in biological applications such as cell imaging. Most fluorescent probes however suffer from limited fluorescence brightness in aqueous media due to aggregation and self-quenching. Their photostability in animal models for an extended period of time is also a concern. One way of improving their photophysical properties is to encapsulate them in a protective matrix to form fluorescent nanoparticles. We have synthesized a set of six through-bond energy transfer cassettes which emit in the 600-800 nm region with Fluorescein or BODIPY as donor and benzophenoxazine dye Nile Red or cyanine dye Cy5 as acceptor. Their photophysical properties in organic and aqueous media were evaluated. Some of these cassettes were encapsulated in silica or calcium phosphate nanoparticles (20 nm in diameter) to improve their solubility and photophysical properties in aqueous media. We also synthesized some water-soluble benzophenoxazine based fluorophores and the impact of different water-soluble groups on their emission characteristics in aqueous media was studied. Selected fluorophores were used for in vitro cellular imaging studies

Encapsulated Energy-transfer Cassettes With Extremely Well Resolved Fluorescent Outputs

This paper concerns the development of water-compatible fluorescent imaging probes with tunable photonic properties that can be excited at a single wavelength. Bichromophoric cassettes 1a-1c consisting of a BODIPY donor and a cyanine acceptor were prepared using a simple synthetic route, and their photophysical properties were investigated. Upon excitation of the BODIPY moiety at 488 nm the excitation energy is transferred through an acetylene bridge to the cyanine dye acceptor, which emits light at approximately 600, 700, and 800 nm, i.e., with remarkable dispersions. This effect is facilitated by efficient energy transfer that gives a quasi-Stokes shift between 86 and 290 nm, opening a huge spectral window for imaging. The emissive properties of the cassettes depend on the energy-transfer (ET) mechanism: the faster the transfer, the more efficient it is. Measurements of rates of ET indicate that a through-bond ET takes place in the cassettes la and 1b that is 2 orders of magnitude faster than the classical through-space, Forster ET. In the case of cassette 1c, however, both mechanisms are possible, and the rate measurements do not allow us to discern between them. Thus, the cassettes 1a-1c are well suited for multiplexing experiments in biotechnological methods that involve a single laser excitation source. However, for widespread application of these probes, their solubility in aqueous media must be improved. Consequently, the probes were encapsulated in calcium phosphate/silicate nanoparticles (diameter ca. 22 nm) that are freely dispersible in water. This encapsulation process resulted in only minor changes in the photophysical properties of the cassettes. The system based on cassette la was chosen to probe how effectively these nanoparticles could be used to deliver the dyes into cells. Encapsulated cassette la permeated Clone 9 rat liver cells, where it localized in the mitochondria and fluoresced through the acceptor part, i.e., red. Overall, this paper reports readily accessible, cyanine-based through-bond ET cassettes that are lypophilic but can be encapsulated to form nanoparticles that disperse freely in water. These particles can be used to enter cells and to label organelles

Tyrosine Kinase Inhibitors for Glioblastoma Multiforme: Challenges and Opportunities for Drug Delivery

Glioblastoma multiforme (GBM) is an aggressive brain tumor with high mortality rates. Due to its invasiveness, heterogeneity, and incomplete resection, the treatment is very challenging. Targeted therapies such as tyrosine kinase inhibitors (TKIs) have great potential for GBM treatment, however, their efficacy is primarily limited by poor brain distribution due to the presence of the blood–brain barrier (BBB). This review focuses on the potential of TKIs in GBM therapy and provides an insight into the reasons behind unsuccessful clinical trials of TKIs in GBM despite the success in treating other cancer types. The main section is dedicated to the use of promising drug delivery strategies for targeted delivery to brain tumors. Use of brain targeted delivery strategies can help enhance the efficacy of TKIs in GBM. Among various drug delivery approaches used to bypass or cross BBB, utilizing nanocarriers is a promising strategy to augment the pharmacokinetic properties of TKIs and overcome their limitations. This is because of their advantages such as the ability to cross BBB, chemical stabilization of drug in circulation, passive or active targeting of tumor, modulation of drug release from the carrier, and the possibility to be delivered via non-invasive intranasal route

Compositions and methods for treating cancer

Provided herein are methods and compositions inter alia for treating diseases, including hyperproliferative diseases, migraine headaches, and depression.Board of Regents, University of Texas Syste