Chemical Approaches to Optimize the Properties of Organic Fluorophores for Imaging and Sensing.

Organic fluorophores are indispensable tools in cells, tissue and in vivo imaging, and have enabled much progress in the wide range of biological and biomedical fields. However, many available dyes suffer from insufficient performances, such as short absorption and emission wavelength, low brightness, poor stability, small Stokes shift, and unsuitable permeability, restricting their application in advanced imaging technology and complex imaging. Over the past two decades, many efforts have been made to improve these performances of fluorophores. Starting with the luminescence principle of fluorophores, this review clarifies the mechanisms of the insufficient performance for traditional fluorophores to a certain extent, systematically summarizes the modified approaches of optimizing properties, highlights the typical applications of the improved fluorophores in imaging and sensing, and indicates existing problems and challenges in this area. This progress not only proves the significance of improving fluorophores properties, but also provide a theoretical guidance for the development of high-performance fluorophores.

"Zero" Intrinsic Fluorescence Sensing-Platforms Enable Ultrasensitive Whole Blood Diagnosis and In Vivo Imaging.

Abnormal physiological processes and diseases can lead to content or activity fluctuations of biocomponents in organelles and whole blood. However, precise monitoring of these abnormalities remains extremely challenging due to the insufficient sensitivity and accuracy of available fluorescence probes, which can be attributed to the background fluorescence arising from two sources, 1) biocomponent autofluorescence (BCAF) and 2) probe intrinsic fluorescence (PIF). To overcome these obstacles, we have re-engineered far-red to NIR II rhodol derivatives that possess weak BCAF interference. And a series of "zero" PIF sensing-platforms were created by systematically regulating the open-loop/spirocyclic forms. Leveraging these advancements, we devised various ultra-sensitive NIR indicators, achieving substantial fluorescence boosts (190 to 1300-fold). Among these indicators, 8-LAP demonstrated accurate tracking and quantifying of leucine aminopeptidase (LAP) in whole blood at various stages of tumor metastasis. Furthermore, coupling 8-LAP with an endoplasmic reticulum-targeting element enabled the detection of ERAP1 activity in HCT116 cells with p53 abnormalities. This delicate design of eliminating PIF provides insights into enhancing the sensitivity and accuracy of existing fluorescence probes toward the detection and imaging of biocomponents in abnormal physiological processes and diseases.

Advances in Multifunctional Chemotherapeutic Prodrugs for Near-infrared Fluorescence Imaging-guided Therapy.

Conventional chemotherapy (CT) is associated with severe side effects and inducible resistance, making it difficult to meet clinical requirements, forcing the development of new multifunctional prodrugs for precision medicine. In recent decades, researchers and clinicians have focused on developing of multifunctional chemotherapeutic prodrugs with tumor-targeting capability, activatable and traceable chemotherapeutic activity, as a powerful tool to improve theranostic outcomes in cancer treatment. The conjugates of near-infrared (NIR) organic fluorophores and chemotherapy reagents create an exciting avenue for real-time monitoring of drug delivery and distribution, as well as the combination of chemotherapy and photodynamic therapy (PDT). Therefore, there are great opportunities for researchers to conceive and exploit multifunctional prodrugs that can visualize chemo-drugs release and tumor treatment in vivo. In this review, the design strategy and the recent progress of multifunctional organic chemotherapeutic prodrugs for activating NIR fluorescence imaging-guided therapy are described and discussed in detail. Finally, the prospects and challenges of multifunctional chemotherapeutic prodrugs for NIR fluorescence imaging-guided therapy are provided.

Metallic Nanoclusters for Cancer Imaging and Therapy.

BACKGROUND: Nanoclusters are made of a few to tens of atoms with a size below 2 nm. Compared with nanoparticles, they exhibited excellent properties, such as tunable fluorescence, ease of conjugation, high quantum yield and biocompatibility, which are highly desired in the development of cancer nanotheranostics. Hence, the metallic nanoclusters have emerged as a newcomer in cancer nanomedicines. This review aims to summarize recently developed approaches to preparing metallic nanoclusters, highlight their applications in cancer theranostics, and provide a brief outlook for the future developments of nanoclusters in nanomedicine. METHOD: We carried out a thorough literature search using online databases. The search was focused on a centered question. Irrelevant articles were excluded after further examination and directly relevant articles were included. The relevant articles were classified by the subjects and the information from these articles was synthesized. RESULTS: One hundred and forty-three articles were included in this review. About eighty articles outlined the development in the synthetic methods of nanoclusters. The synthesis approaches include chemical reduction, photoreduction and so on. The progress in the application of gold and silver nanoclusters to cancer theranostics was described in fifteen and eight articles, respectively. The rest articles were about the advancements in the use of other metal nanoclusters and nanocluster nanocomposites as cancer theranostic agents. CONCLUSION: This review summarizes the synthesis and use of metallic nanoclusters or their nanocomposites as cancer theranostic agents. It confirms their importance, advantages and potentials in serving as a new generation of cancer theranostics in clinics.

Phosphorogenic sensors for biothiols derived from cyclometalated iridium(III) polypyridine complexes containing a dinitrophenyl ether moiety.

We report the synthesis and characterization of three cyclometalated iridium(III) polypyridine complexes containing a 2,4-dinitrophenyl ether moiety [Ir(pq)2(N^N)](PF6) (Hpq=2-phenylquinoline; N^N=4-(N-(4-(2,4-dinitrophenoxy)benzyloxy)carbonyl)aminomethyl-4'-methyl-2,2'-bipyridine (bpy-dinitro-1) (1a), 4-(2,4-dinitrophenoxy)methyl-4'-methyl-2,2'-bipyridine (bpy-dinitro-2) (2a), 4-(4-(2,4-dinitrophenoxy)phenyl)-2,2'-bipyridine (bpy-dinitro-3) (3a)) as intracellular sensors for biothiols. Due to the quenching effect of the dinitroaromatic moiety, these complexes were extremely weakly emissive. Upon the reaction with biothiols, however, the emission was turned on as a consequence of the departure of the quenching unit. The results from a range of experiments demonstrated that complex 1a was noncytotoxic under the conditions used for confocal imaging, showed facile cellular uptake, and can serve as a phosphorogenic intracellular sensor for biothiols including glutathione (GSH) and hydrogen sulfide.

High-Density Lipoproteins: Nature's Multifunctional Nanoparticles.

High-density lipoproteins (HDL) are endogenous nanoparticles involved in the transport and metabolism of cholesterol, phospholipids, and triglycerides. HDL is well-known as the "good" cholesterol because it not only removes excess cholesterol from atherosclerotic plaques but also has anti-inflammatory and antioxidative properties, which protect the cardiovascular system. Circulating HDL also transports endogenous proteins, vitamins, hormones, and microRNA to various organs. Compared with other synthetic nanocarriers, such as liposomes, micelles, and inorganic and polymeric nanoparticles, HDL has unique features that allow them to deliver cargo to specific targets more efficiently. These attributes include their ultrasmall size (8-12 nm in diameter), high tolerability in humans (up to 8 g of protein per infusion), long circulating half-life (12-24 h), and intrinsic targeting properties to different recipient cells. Various recombinant ApoA proteins and ApoA mimetic peptides have been recently developed for the preparation of reconstituted HDL that exhibits properties similar to those of endogenous HDL and has a potential for industrial scale-up. In this review, we will summarize (a) clinical pharmacokinetics and safety of reconstituted HDL products, (b) comparison of HDL with inorganic and other organic nanoparticles,