Mechanistic analysis of viscosity-sensitive fluorescent probes for applications in diabetes detection.

Diabetes is one of the most detrimental diseases affecting the human life because it can initiate several other afflictions such as liver damage, kidney malfunctioning, and cardiac inflammation. The primary method for diabetes diagnosis involves the analysis of blood samples to quantify the level of glucose, while secondary diagnostic methods involve the qualitative analysis of obesity, fatigue, etc. However, all these symptoms start showing up only when the patient has been suffering from diabetes for a certain period of time. In order to avoid such delay in diagnosis, the development of specific fluorescent probes has attracted considerable attention. Prominent biomarkers for diabetes include abundance of certain analytes in blood serum, e.g., glucose, methylglyoxal, albumin, and reactive oxygen species; high intracellular viscosity; alteration of enzyme functionality, etc. Among these, high viscosity can greatly affect the fluorescence properties of various chromophores owing to the environment sensitivity of fluorescence spectra. In this review article, we have illustrated the application of some prominent fluorophores such as coumarin, BODIPY, xanthene, and rhodamine in the development of viscosity-dependent fluorescent probes. Detailed mechanistic aspects determining the influence of viscosity on the fluorescent properties of the probes have also been elaborated. Fluorescence mechanisms that are directly affected by the high-viscosity heterogeneous microenvironment are based on intramolecular rotations like twisted intramolecular charge transfer (TICT), aggregation-induced emission (AIE), and through-bond energy transfer (TBET). In this regard, this review article will be highly useful for researchers working in the field of diabetes treatment and fluorescent probes. It also provides a platform for the planning of futuristic clinical translation of fluorescent probes for the early-stage diagnosis and therapy of diabetes.

Mitochondria-localized in situ generation of rhodamine photocage with fluorescence turn-on enabling cancer cell-specific drug delivery triggered by green light.

In this work, we have developed a rhodamine dye based water-soluble, mitochondria-indicating photocage, which gets activated in the mitochondria producing a fluorescent signal and on-demand releases the caged anticancer drug, chlorambucil, in the cancer cells selectively upon irradiation of green light.

Quinoline H2S donor decorated fluorescent carbon dots: visible light responsive H2S nanocarriers.

Recent studies have shown that the utility of nanocarriers for the transportation of gaseous signalling molecules to their target site in a biological environment is an effective approach. In this work, we have developed for the first time visible light responsive nanocarriers for the effective release of H2S. Our newly developed nanocarriers for H2S release are constructed using two main ingredients: fluorescent carbon dots and quinoline as an H2S donor. The developed nanocarriers provided interesting properties like good solubility under physiological conditions, excellent fluorescence properties and efficient release ability of H2S with good quantum yield upon visible light irradiation. In vitro studies revealed that our designed nanocarriers exhibited abilities like efficient cellular internalization and good biocompatibility.

A water soluble light activated hydrogen sulfide donor induced by an excited state meta effect.

We have utilized an m-amino benzyl based photoremovable protecting group (PRPG) to develop a new water soluble H2S donor. It efficiently releases H2S on demand in a spatio-temporally controlled fashion by an excited state "meta effect" with good chemical and photochemical quantum yield in an aqueous environment. The efficient photorelease of H2S under physiological conditions was also demonstrated by in vitro studies.

o-Hydroxycinnamate for sequential photouncaging of two different functional groups and its application in releasing cosmeceuticals.

We demonstrated a new approach for the sequential photouncaging of two different functional groups from o-hydroxycinnamate. The second caged molecule initially remains in the locked state and is released only after attaining its unlocked state upon in situ generation of the second phototrigger, i.e., coumarin, thereby leading to the sequential release of alcohol and carboxylic acid. We have utilised the above strategy for the controlled release of cosmeceutical agents.

Push-Pull Stilbene: Visible Light Activated Photoremovable Protecting Group for Alcohols and Carboxylic Acids with Fluorescence Reporting Employed for Drug Delivery.

For the first time we have utilized push-pull stilbene as a visible light activated photoremovable protecting group (PRPG) for the uncaging of alcohols and carboxylic acids. The PRPG efficiently release caged molecules with good photochemical quantum yield. It is capable of monitoring the release in real time owing to its fluorescence "turn on" phenomenon upon photorelease in polar medium. The efficient photorelease and real time monitoring abilities of push-pull stilbene were employed for in vitro drug delivery.

Metallaphotoredox-Mediated Csp2-H Hydroxylation of Arenes under Aerobic Conditions.

The direct hydroxylation of 2-arylpyridines and 2-arylbenzothiazoles via the merger of organic photoredox and metal catalysis is reported where 4CzIPN is used as the visible-light photocatalyst and Pd(OAc)2 as the metal catalyst. This method has been employed to synthesize organic molecules exhibiting excited-state intramolecular proton transfer properties for generating tunable luminescence responses.

A dual-analyte probe: hypoxia activated nitric oxide detection with phototriggered drug release ability.

A new strategy for the detection of hypoxia and NO succeeded by photocontrolled delivery of an anticancer agent has been demonstrated. The developed system is able to produce distinct responses (dual channel) upon interaction with hypoxia and NO. This probe can also release anticancer drugs upon photoirradiation acting potentially as both a dual-analyte imaging agent and a prodrug.

ESIPT-induced fluorescent o-hydroxycinnamate: a self-monitoring phototrigger for prompt image-guided uncaging of alcohols.

o-Hydroxycinnamate derivatives are well-known phototriggers for fast and direct release of alcohols and amines without proceeding through the cleavage of carbonate or carbamate linkages. Despite these unique features, o-hydroxycinnamates lack extensive applications in biological systems mainly because of their non-fluorescent nature. To overcome this limitation, we have attached a 2-(2'-hydroxyphenyl) benzothiazole (HBT) moiety, capable of rapid excited-state intramolecular proton transfer (ESIPT) to the o-hydroxycinnamate group. The ESIPT effect induced two major advantages to the o-hydroxycinnamate group: (i) large Stokes' shifted fluorescence (orange colour) properties and (ii) distinct fluorescence colour change upon photorelease. In vitro studies exhibited an image guided, photoregulated release of bioactive molecules by the o-hydroxycinnamate-benzothiazole-methyl salicylate conjugate and real-time monitoring of the release action.

Photoresponsive real time monitoring silicon quantum dots for regulated delivery of anticancer drugs.

Recently, photoresponsive nanoparticles have been widely used to develop drug delivery systems (DDSs) wherein light is used as an external stimulus to trigger drug release in a spatially and temporally controlled fashion. Real time monitoring DDSs are also gaining much interest due to their capability of monitoring drug release in situ. In this context we designed a new photoresponsive real time monitoring nanoparticle based on photoluminescent silicon quantum dots (SiQDs) using the o-nitrobenzyl (ONB) derivative as a phototrigger for the controlled release of anticancer drug chlorambucil (Cbl). The strong fluorescence of SiQDs was initially quenched by ONB. Upon irradiation ONB triggered the release of the drug switching on the fluorescence of SiQDs to monitor the drug release. We reported a new and simple strategy to synthesise amine functionalised silicon quantum dots and covalently conjugated phototrigger ONB with caged anticancer drug Cbl onto it. Newly designed photoresponsive theranostic ONBCbl-SiQDs performed three important functions: (i) nanocarriers for drug delivery, (ii) controlled drug release under both one photon and two-photon excitation, and (iii) photoswitchable fluorescent nanoparticles for real-time monitoring of drug release based on the photoinduced electron transfer (PET) process. In vitro biological studies revealed the efficient cellular internalisation and cancer cell destruction ability of ONBCbl-SiQDs upon photoirradiation. ONBCbl-SiQDs exhibit a successful example of combining multiple functions into a single system for drug delivery systems.