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The development of an efficient two-photon responsive HPQ-based fluorescent organic nanoprodrug for H2S release against oxidative stress.

Hypoxia-induced intratumoral heterogeneity poses a major challenge in tumor therapy due to the varying susceptibility to chemotherapy. Moreover, the spatial distribution patterns of hypoxic and normoxic tissues makes conventional combination therapy less effective. In this study, a tumor-acidity and bioorthogonal chemistry mediated in situ size transformable nanocarrier (NP@DOX

In recent times, organelle-targeted drug delivery systems have gained tremendous attention due to the site-specific delivery of active drug molecules, resulting in enhanced bioefficacy. In this context, a phototriggered drug delivery system (DDS) for releasing an active molecule is superior, as it provides spatial and temporal control over the release. So far, a near-infrared (NIR) light-responsive organelle-targeted DDS has not yet been developed. Hence, we introduced a two-photon NIR light-responsive lysosome-targeted "AIE + ESIPT" active single-component DDS based on the naphthalene chromophore. The two-photon absorption cross section of our DDS is 142 GM at 850 nm. The DDS was converted into pure organic nanoparticles for biological applications. Our nano-DDS is capable of selective targeting, AIE luminogenic imaging, and drug release within the lysosome.

This review describes the characteristic features of simple and nascent N-centered azide radical, and its unique reactivity in fine chemical synthesis with detailed mechanistic discussions.

Controlled release of hydrogen sulfide (H2S), an important gasotransmitter that plays a significant role in the regulation of various physiological activities.

The widespread occurrence of infections from multidrug-resistant (MDR) bacteria is a global health problem. It has been amplified over the past few years due to the increase in adaptive traits in bacteria and lack of advanced treatment strategies. Because of the low bioavailability and limited penetration at infected sites, the existing antibiotics often fail to resist bacterial growth. Recently, developed stimuli-responsive drug delivery systems and combinatorial therapeutic systems based on nanoparticles, metal-organic frameworks, hydrogels, and organic chromophores offer the ability to improve the therapeutic efficacy of antibiotics by reducing drug resistance and other side effects. These therapeutic systems have been designed with the relevant chemical and physical properties that respond to specific triggers resulting in spatiotemporal controlled release and site-specific transportability. This review highlights the latest development of single and dual/multistimuli-responsive antibiotic delivery systems for combination therapies to treat MDR bacterial infections and biofilm eradication.

We demonstrated for the first time without any chemical modification the two-photon absorption (TPA) cross-section can be enhanced and red-shifted to the near-infrared (NIR) region by the ground-state proton-transfer (GSPT) process. Using GSPT, we developed a simple binol-based aggregation-induced emission (AIE)-fluorogenic phototrigger having a large two-photon uncaging cross-section in the "phototherapeutic window". As a proof of concept, we showed our phototrigger for the release of two different anticancer drugs in the NIR region.

The recent resurgence of synergistic palladium and visible-light-induced photoredox catalysis has led to a paradigm shift in Pd-catalyzed organic synthesis that encompasses unconventional modes of bond formation via cross-coupling, C–H bond activation, C–X bond functionalization in organic molecules, and access to various elusive reaction pathways under mild conditions. Moreover, the ability to reroute the traditional Pd-catalyzed reactions via alternative Pd/radical-mediated pathways can lead to improvements in the reaction rate, conditions, functional group compatibility, and/or substrate scopes. The combination of a suitable (metalla- or organo-)photocatalyst with conventional active Pd0 or PdII catalyst has been employed as an efficient dual catalytic system for various C–C and C–O cross-coupling reactions. In the course of the reaction, the organopalladium complex captures the incipient radical species in a rebound process, resulting in a transitory PdIII or PdIV intermediate to furnish cross-coupled products mostly via the reductive elimination pathway. This Minireview discusses all advances in the design and development of these cooperative catalytic reactions over the past few years, demonstrates their unique mechanistic features, and highlights selective examples for substrate scopes.

This report presents the visible-light-assisted synthesis of aryl nitriles from easily accessible alcohols or methyl arenes in the presence of O2 . Organic photoredox catalyst, 4CzIPN (1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene), induces single electron transfer (SET) from azide N3 - and generates azide radical N3 ⋅.The photogenerated N3 ⋅ abstracts H atom from α-C-H bond of benzylic system, which provides aldehyde and hydrazoic acid (HN3 ) in situ. This reaction subsequently forms azido alcohol intermediate that transforms into nitrile with the assistance of triflic acid (Bronsted acid). A range of alcohols and methyl arenes successfully underwent cyanation at room temperature with good to excellent yields and showed good functional group tolerance.

The β-carboline moiety, substituted at the C1 and C3 benzylic positions with a leaving group, has been demonstrated for the first time as a photoremovable protecting group for time-dependent sequential release of two (same or different) carboxylic acids upon one- and two-photon light irradiation. Density functional theory calculations suggest that the electronic environment of the β-carboline moiety at C1 and C3 positions plays a key role in the rate of photorelease.

Developing green or red light-activated drug delivery systems (DDSs) for cancer treatment is highly desirable. Herein, we have reported a green light-responsive single component-based organic fluorescence nano-DDS by simply anchoring 2-hydroxy-6-naphthacyl (phototrigger) on both sides of the 1,5-diaminonaphthalene (DAN) chromophore. This green light (λ ≥ 500 nm)-activated DDS released two equivalents of the anticancer drug (valproic acid) in a spatio-temporally controlled manner. Our photoresponsive DDS [DAN-bis(HO-Naph-VPA)] exhibited interesting properties such as excited-state intramolecular proton transfer (ESIPT) accompanied with aggregation-induced emission (AIE) phenomena. AIE initiated the photorelease, and ESIPT enhanced the rate of the photorelease. Further

A phenothiazine-based photoremovable protecting group (PRPG) for single and dual release of carboxylic acids was developed. The change in the oxidation state of the sulfur atom of the phenothiazine PRPG resulted in singlet oxygen generation, rather than photorelease. The difference in the photochemistry between oxygen-free and oxygen-functionalized phenothiazine was investigated and supported by DFT calculations.

We studied the dispersion of nonlinear refraction coefficient (n2) of carbon dots by the Z-scan technique at different photon energies (2.38-2.48 eV). It shows positive n2 at 2.38 eV and negative n2 at other excitations.

In recent times, organelle-targeted drug delivery systems gained tremendous attention due to the site specific delivery of active drug molecules resulting in enhanced bioefficacy. In this context, the phototriggered drug delivery system (DDS) for releasing an active molecule is superior as it provides spatial and temporal control over the release. So far, near infrared (NIR) light responsive organelle targeted DDS has not yet been developed. Hence, we introduced a two-photon NIR-light responsive lysosome targeted ʽAIE + ESIPTʼ active single component DDS based on naphthalene chromophore. The Two-photon absorption cross-section of our DDS is 142 GM at 850 nm. The DDS was converted into pure organic nanoparticles for biological applications. Our nano-DDS is capable of selective targeting, AIE-luminogenic imaging, and drug release within the lysosome. In vitro studies using cancerous cell lines showed that our single component photoresponsive nanocarrier exhibited enhanced cytotoxicity and real-time monitoring ability of the drug release.

The development of Photoremovable protecting groups (PRPGs), which can be activated in the ʽphototherapeutic windowʼ for biological applications, is highly challenging. Only PRPGs based on BODIPY dye have been developed so far, which can be excited ≥600 nm. Herein, we developed for the first time NIR dye hydroxystyryl dicyanomethylene-4H-pyran (DCM) as a PRPG that can be operated in the phototherapeutic window. Ours easily synthesized DCM photocages efficiently released aromatic and aliphatic carboxylic acids in an aqueous solution on irradiation using the light of wavelength ≥600 nm and 650 nm, separately. As an application, we used our DCM-PRPG as a single component nanocarrier drug delivery system (DDS) to uncage valproic acid (a known histone deacetylase inhibitor) for cancer treatment. In vitro studies revealed that our DDS, hydroxystyryl dicyanomethylene-4H-pyran valproic acid conjugate nanoparticles (DCM-VPA-NPs) exhibited good cellular internalization, biocompatibility, and enhanced cytotoxicity upon irradiation.

The development of Photoremovable protecting groups (PRPGs), which can be activated in the ʽphototherapeutic windowʼ for biological applications, is highly challenging. Only PRPGs based on BODIPY dye have been developed so far, which can be excited ≥600 nm. Herein, we developed for the first time NIR dye hydroxystyryl dicyanomethylene-4H-pyran (DCM) as a PRPG that can be operated in the phototherapeutic window. Ours easily synthesized DCM photocages efficiently released aromatic and aliphatic carboxylic acids in an aqueous solution on irradiation using the light of wavelength ≥600 nm and 650 nm, separately. As an application, we used our DCM-PRPG as a single component nanocarrier drug delivery system (DDS) to uncage valproic acid (a known histone deacetylase inhibitor) for cancer treatment. In vitro studies revealed that our DDS, hydroxystyryl dicyanomethylene-4H-pyran valproic acid conjugate nanoparticles (DCM-VPA-NPs) exhibited good cellular internalization, biocompatibility, and enhanced cytotoxicity upon irradiation.

This report presents the oxygenation of C-H bonds via the merger of photocatalysis and Pd catalysis. Herein, we describe the utilization of a photocatalyst to oxidize an organopalladium(II) intermediate to high-valent Pd

We report a two-photon responsive drug delivery system (DDS), namely, p-hydroxyphenacyl-naphthalene-chlorambucil (pHP-Naph-Cbl), having a two-photon absorption (TPA) cross-section of ≥20 GM in the phototherapeutic window (700 nm). Our DDS exhibited both AIE and ESIPT phenomena, which were utilized for the real-time monitoring of anti-cancer drug release.

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 wavelength-orthogonal photocleavable monochromophoric linker was developed that is based on a 3-acetyl-9-ethyl-6-methylcarbazole (AEMC) moiety substituted at both the phenacyl and benzylic positions with different carboxylic acids. The different carboxylic acids were released sequentially upon irradiation with light of λ ≥ 365 nm and λ ≥ 290 nm, respectively.

Persulfides have been considered as potential signaling compounds similar to the H2S in "S-persulfidation", a sulfur-mediated redox cycle. The research of this sulfur-mediated species is hindered because of the lack of efficient persulfide donors. In this current study, we have developed one- and two-photon-activated persulfide donors based on an o-nitrobenzyl (ONB) phototrigger, which releases the biologically active persulfide (N-acetyl l-cysteine persulfide, NAC-SSH) in a spatiotemporal manner. Next, we have demonstrated the detection of persulfide release both qualitatively and quantitatively using the well-known "turn on" fluorescence probe, that is, monobromobimane, and the trapping agent, that is, 2,4-dinitrofluorobenzene, respectively. Furthermore, we examined the cytotoxicity of synthesized persulfide donors on HeLa cells and the cytoprotective ability in the highly oxidizing cellular environment.

Light-responsive fluorescent organic nanoparticles (NPs) based on tetraphenylethylene (TPE) have been developed for the release of 4 equiv of chlorambucil (Cbl) and photodynamic therapy (PDT) utili...

In the last two decades, light responsive nano drug delivery systems (DDSs) have gained considerable importance, particularly in the area of biology and medicine. In general, light responsive nano DDSs are bicomponent and constructed using two ingredients, namely a nanocarrier and a phototrigger. The synthesis of these bicomponent nano DDSs requires multiple steps, which limits their applications. Hence, we have reported single component light responsive nano DDSs using fluorescent organic nanoparticles (FONPs) which acted both as a nanocarrier and a phototrigger. This feature article provides an overview of recently developed light responsive single component FONPs and their applications in the regulated release of anticancer drugs, gasotransmitters, antibacterial agents, and pesticides, and also as efficient PDT agents. We have summarised the synthesis, characterisation, and photophysical, photochemical, and in vitro behaviours of these light responsive FONPs. In addition, we also discussed the advantages of using FONPs as a nano DDS for cellular studies like: excellent biocompatibility, efficient cellular internalisation, real time monitoring of the drug release ability inside the cells, and enhanced cytotoxicity due to regulated release of bioactive molecules inside the cells.

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.

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.

Hydrogen persulfide (H2S2) plays an important role in sulfur-based redox signaling mechanisms. Herein, we developed a visible light activated ESIPT based H2S2 donor using a p-hydroxyphenacyl phototrigger. The unique feature of the designed H2S2 donor system is the ability to monitor the H2S2 release in real time through a non-invasive fluorescence color change approach, with the color changing from green to blue. Next, we demonstrated the detection and quantification of H2S2 using a fluorescein based "turn-on" fluorescent probe. Furthermore, in vitro studies of the designed H2S2 donor demonstrated the real-time monitored H2S2 release and cytoprotective ability in the highly oxidizing cellular environment of MDA-MB-468 cells.

In this work, we depleted glutathione (GSH) by releasing SO2 with internal stimulus GSH itself, and also selectively marked the cancer cells followed by release of anticancer drug using another orthogonal stimulus i.e., two-photon (TP) NIR light by a single naphthalene based chromophore (TP absorbance 77 GM and uncaging cross-section 21 GM). We demonstrated the improved therapeutic efficacy of chlorambucil by the stepwise dual stimuli approach and dual surveillance of both the drug uncaging process in real-time using in vitro studies.

The present study involves the adsorption of hexavalent Chromium(Cr(VI)) using chitosan grafted graphene oxide (CS-GO) nanocomposite in batch mode. The CS-GO nanocomposite material was prepared by ultrasonic irradiation technique. The CS-GO adsorbent was characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and Tunnelling electron microscopy (TEM), followed by Cr(VI) adsorption studies. The adsorption capacity of 104.16 mg/g was achieved at pH 2.0, in the contact time of 420 min. The adsorption process was described by the pseudo second order kinetic and Langmuir isotherm model. The nano-microstructural investigation validates the successful adsorption of Cr(VI) on CS-GO nanocomposite. The CS-GO material is recyclable up to 10 cycles with the minimum loss in adsorption capacity.

One- and two-photon activated sulfur dioxide donors based on a 4,5-dimethoxy-2-nitrobenzyl phototrigger have been developed. The designed donors have the ability to release not only SO2 but also a hydroxy-compound in a simultaneous manner. Furthermore, we demonstrated their application in combinatorial therapy by the dual release of SO2 and an active drug, i.e. ferulic acid ethyl ester (FAEE) with self-monitoring ability. Next, we investigated the in vitro cellular uptake and the capability of SO2 generation from the donors using a well-known coumarin-hemicyanine fluorescent probe. Finally, we evaluated the antibacterial activity of the designed donors (5a, 5b and 6) by broth dilution and agar well diffusion methods on E. cloacae cells (MTCC 509). The results show that the donor 5a exhibits enhanced antibacterial efficacy compared to 5b and 6, due to the synergetic effect of dually released SO2 and FAEE.

We have developed a new targeted image-guided photoresponsive drug delivery system (DDS) based on a dual locking strategy. Excitation of the DDS by fluorescent light results in the first unlocking and activation of the drug, and allows real-time monitoring of the prodrug. Extended irradiation results in a second unlocking, giving drug release within cancer cells.

We have developed an ESIPT based drug delivery system (DDS), Cou–Benz–Cbl conjugate, by incorporating a benzothiazole group at the 8th position of the 7-hydroxy-coumarin moiety for pH sensitive fluorescence properties and photocontrolled release of the anticancer drug chlorambucil. The Cou–Benz–Cbl conjugate exhibited unique photophysical properties like good absorbance at around 350 nm, a large Stokes shift (∼151 nm) and pH sensitive fluorescence properties. The pH sensitive fluorescence properties of the Cou–Benz–Cbl conjugate can be ascribed to an ESIPT turn “on and off” mechanism. At physiological pH, the ESIPT gets turned “off” and a blue fluorescence of the coumarin moiety was observed, but at acidic pH, the ESIPT gets turned “on” and a green fluorescence was noted. Photolysis of the Cou–Benz–Cbl conjugate using UV light of wavelength ≥365 nm resulted in the efficient release of the anticancer drug chlorambucil. Cellular uptake studies revealed that the Cou–Benz–Cbl conjugate was easily internalized inside the cancer cells. Further, an MTT assay showed that the Cou–Benz–Cbl conjugate has a good biocompatibility and low cytotoxicity towards the MDA-MB-231 cell line, whereas upon exposure to UV light, the Cou–Benz–Cbl conjugate exhibited enhanced cytotoxicity compared to the free drug due to the effective release of the anticancer drug chlorambucil inside the cancer cell.

In spite of inventing several anticancer agents the clinical payoff still remains unsatisfactory because of their severe host toxicity due to their nonspecific biodistribution in the body. To achieve high efficiency in anti-cancer drug delivery, thus, we designed and developed a single component photoresponsive drug delivery system, a fusion of two platforms spiropyran and coumarin, which synchronizes two controlling factors: first, the lower pH of cancer tissue, which acts as an internal control and leads to the ring opening of spiropyran resulting in a distinct colour change and fluorescence activation of coumarin; and second, the release of the anti-tumor drug by the externally controlled light. Highly fluorescent nature and promising biocompatibility make the SP–Cou–Cbl system suitable for cell imaging and in vitro studies.

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.

The anti-tumor activity of Cu complexes is well established in cancer research. We developed a biotin-tagged Cu-chelating prodrug that is activated by one-photon and two-photon irradiation for the target-specific and spatio-temporally controlled in situ generation of a Cu complex. In this way, we transform copper from a "cancer-promoting" agent to an anticancer agent.

A magnetically modified graphene oxide/chitosan/ferrite (GCF) nanocomposite material was synthesized and exploited for removal of Chromium(VI) from aqueous solution. The GCF nanocomposite material was characterized by powder-X-ray diffraction (powder-XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscope- energy dispersive X-ray (SEM-EDX) analysis, transmission electron microscopy (TEM) thermogravimetric analysis (TGA), UV–vis diffusive reflectance spectra and Brunauer–Emmett–Teller (BET) analysis. The effect of pH, adsorbent dose, contact time and initial Cr(VI) metal ion concentration were studied in batch process. The GCF nanocomposite material showed an adsorption capacity of 270.27 mg g−1 for Cr(VI) at pH 2.0. The adsorption mechanism of GCF adsorbent material was well described by Langmuir isotherm and pseudo second order kinetic model, with a high regression coefficient (

In the present study, a novel nanocomposite adsorbent material was synthesized using chitosan (CS), graphene oxide (GO) and metal organic framework (MOF [Zn(BDC)(DMF)]) for the adsorption of Chromium (VI) heavy metal from aqueous solution. The characterization of the prepared GO-CS@MOF [Zn(BDC)(DMF)] was accomplished by powder X-ray diffraction (PXRD), Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and Brunauer–Emmett–Teller (BET), followed by Cr(VI) adsorption-desorption studies. Experimental parameters such as effect of pH, temperature, contact time, adsorbent dosage and shaking speed were optimized. The GO-CS@MOF [Zn(BDC)(DMF)] showed an adsorption capacity of 144.92 mg/g for Cr(VI) at pH 3.0. Thermodynamic properties (ΔGo, ΔHo, ΔSo) have been calculated and the process is found to be endothermic, favourable and spontaneous. The adsorption study of Cr(VI) by GO-CS@MOF [Zn(BDC)(DMF)] comprises both kinetic and isotherm studies. The equilibrium adsorption followed Langmuir model and adsorption reaction was found to be pseudo-second order confirming chemisorption. The developed GO-CS@MOF [Zn(BDC)(DMF)] nanocomposite material will serve as a new type of platform for removing Cr(VI) from wastewater.

In this paper, we have developed a light-activated single component fluorescent organic nanoparticles for synergistic combination therapy (chemo-photodynamic therapy) utilizing the combined benefits of aggregation-induced emission (AIE) and excited-state intramolecular proton transfer (ESIPT) phenomena. The single-component organic nanoparticles were synthesized by coupling tetraphenylethylene (TPE) moiety with the p-hydroxy phenacyl-chlorambucil conjugate. Then, tetraphenylene-p-hydroxyphenacyl-chlorambucil (TPE-pHP-Cbl) nanoparticles were prepared by a simple reprecipitation technique. Our designed TPE-pHP-Cbl NPs exhibited the unique benefits such as (i) aggregation-induced emission enhancement, (ii) large Stoke’s shift, (iii) the photoirradiation wavelength >410 nm, (iv) the drug release occurs only in the aggregated state upon photolysis, (v) PDT activity, (vi) real-time monitoring of drug release by a noninvasive fluorescence color change approach, and (vii) PDT activity of the released photoproduct...

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.