Förster Resonance Energy Transfer Research Articles

Portable Near-Infrared to Near-Infrared Platform for Homogeneous Quantification of Biomarkers in Complex Biological Samples.

Förster resonance energy transfer (FRET)-based homogeneous immunoassay obviates tedious washing steps and thus is a promising approach for immunoassays. However, a conventional FRET-based homogeneous immunoassay operating in the visible region is not able to overcome the interference of complex biological samples, thus resulting in insufficient detection sensitivity and poor accuracy. Here, we develop a near-infrared (NIR)-to-NIR FRET platform (Ex = 808 nm, Em = 980 nm) that enables background-free high-throughput homogeneous quantification of various biomarkers in complex biological samples. This NIR-to-NIR FRET platform is portable and easy to operate and is mainly composed of a high-performance NIR-to-NIR FRET pair based on lanthanide-doped nanoparticles (LnNPs) and a custom-made microplate reader for readout of NIR luminescence signals. We demonstrate that this NIR-to-NIR FRET platform is versatile and robust, capable of realizing highly sensitive and accurate detection of various critical biomarkers, including small molecules (morphine and 1,25-dihydroxyvitamin D), proteins (human chorionic gonadotropin), and viral particles (adenovirus) in unprocessed complex biological samples (urine, whole blood, and feces) within 5-10 min. We expect this NIR-to-NIR FRET platform to provide low-cost healthcare for populations living in resource-limited areas and be widely used in many other fields, such as food safety and environmental monitoring.

Experimental evidence on the feasibility of employing a replica symmetry breaking classification random laser.

Replica symmetry breaking (RSB) has been introduced in a random laser to investigate the interactions between disorder and fluctuations. In this work, the dynamic difference between four non-energy transfer and Förster resonance energy transfer (FRET)-assisted random laser systems is investigated based on RSB. It is found that FRET is one of the key factors influencing RSB, and it is demonstrated that RSB in a random laser is not robust. This dynamic difference can be attributed to the different disorders induced by the gain mechanism in different random laser systems. This provides experimental evidence and theoretical support for the classification feasibility of RL with different emission mechanisms employing RSB.

De Novo Designed Cell-Penetrating Peptide Self-Assembly Featuring Distinctive Tertiary Structure.

Recent attention has focused on the de novo design of proteins, paralleling advancements in biopharmaceuticals. Achieving protein designs with both structure and function poses a significant challenge, particularly considering the importance of quaternary structures, such as oligomers, in protein function. The cell penetration properties of peptides are of particular interest as they involve the penetration of large molecules into cells. We previously suggested a link between the oligomerization propensity of amphipathic peptides and their cell penetration abilities, yet concrete evidence at cellular-relevant concentrations was lacking due to oligomers' instability. In this study, we sought to characterize oligomerization states using various techniques, including X-ray crystallography, acceptor photobleaching Förster resonance energy transfer (FRET), native mass spectrometry (MS), and differential scanning calorimetry (DSC), while exploring the function related to oligomer status. X-ray crystallography revealed the atomic structures of oligomers formed by LK-3, a bis-disulfide bridged dimer with amino acid sequence LKKLCLKLKKLCKLAG, and its derivatives, highlighting the formation of hexamers, specifically the trimer of dimers, which exhibited a stable hydrophobic core. FRET experiments showed that LK-3 oligomer formation was associated with cell penetration. Native MS confirmed higher-order oligomers of LK-3, while an intriguing finding was the enhanced cell-penetrating capability of a 1:1 mixture of l/d-peptide dimers compared to pure enantiomers. DSC analysis supported the notion that this enantiomeric mixture promotes the formation of functional oligomers, crucial for cell penetration. In conclusion, our study provides direct evidence that amphipathic peptide LK-3 forms oligomers at low nanomolar concentrations, underscoring their significance in cell penetration behavior.

Cascade Förster resonance energy transfer between layered silicate edge-linked chromophores

Förster resonance energy transfer (FRET) serves as a critical mechanism to study intermolecular interactions and the formation of macromolecular assemblies. Cascade FRET is a multi-step FRET process which can overcome limitations associated with traditional single-step FRET. Herein, a novel organic–inorganic hybrid composed of a nile red derivative attached to the edge of the layered silicate clay Laponite (Lap-NR) was used to facilitate cascade FRET between Laponite sheets. Utilizing naphthalene-diimide edge-modified Laponite (Lap-NDI) as the initial donor, Rhodamine 6G on the basal surface of Laponite as the first acceptor, and Lap-NR as the second acceptor, cascade FRET was achieved. The influence of solvent composition in a DMF/water mixture on cascade FRET was investigated, revealing that a higher water content led to an enhancement of the cascade FRET process, which is attributed to increased aggregation-induced emission of Lap-NDI and the enhanced quantum yield of R6G in water. This study provides a unique approach to achieve cascade FRET by taking advantage of the anisotropic surface chemistry of a two-dimensional nanomaterial, providing a colloidally-driven alternative with improved tunability compared to macromolecular routes. The flexibility and simplicity of this approach will advance the state of the art of organic–inorganic hybrids for applications in optoelectronics, sensors, and hybrid photovoltaics.

Quantum Dot-Based FRET Nanosensors for Talin-Membrane Assembly and Mechanosensing.

Understanding the mechanisms of assembly and disassembly of macromolecular structures in cells relies on solving biomolecular interactions. However, those interactions often remain unclear because tools to track molecular dynamics are not sufficiently resolved in time or space. In this study, we present a straightforward method for resolving inter- and intra-molecular interactions in cell adhesive machinery, using quantum dot (QD) based Förster resonance energy transfer (FRET) nanosensors. Using a mechanosensitive protein, talin, one of the major components of focal adhesions, we are investigating the mechanosensing ability of proteins to sense and respond to mechanical stimuli. First, we quantified the distances separating talin and a giant unilamellar vesicle membrane for three talin variants. These variants differ in molecular length. Second, we investigated the mechanosensing capabilities of talin, i.e., its conformational changes due to mechanical stretching initiated by cytoskeleton contraction. Our results suggest that in early focal adhesion, talin undergoes stretching, corresponding to a decrease in the talin-membrane distance of 2.5 nm. We demonstrate that QD-FRET nanosensors can be applied for the sensitive quantification of mechanosensing with a sub-nanometer accuracy.

Functionalizing Surfaces by Physical Vapor Deposition To Measure the Degree of Nanoscale Contact Using FRET.

Adhesion between solid materials is caused by intermolecular forces that only take place if the adhering surfaces are at nanoscale contact (NSC) (i.e., 0.1-0.4 nm. To study adhesion, NSC can be evaluated with Förster Resonance Energy Transfer (FRET). FRET uses the interaction of compatible fluorescence molecules to measure the nanometer distance between bonded surfaces. For this, each surface is labeled with one fluorescence dye, named the Donor or Acceptor. If these molecules are in NSC, a nonradiative Donor-Acceptor energy transfer will occur and can be detected using FRET spectroscopy. Here, for the first time, we introduce an innovative concept of a FRET-based NSC measurement employing dye-nanolayer films prepared by a physical vapor deposition (PVD). The dye nanolayers were prepared by PVD from the vaporization of the Donor and Acceptor molecules separately. The selected molecules, 7-Amino-4-methyl-cumarin (C120) and 5(6)-Carboxy-2',7'-dichlor-fluorescein (CDCF), present high quantum yields (QY, QYD = 0.91 and QYA = 0.64) and a low FRET distance range of 0.6-2.2 nm, adequate for the study of NSC. The produced dye-nanolayer films exhibit a uniform dye distribution (verified by atomic force microscopy) and suitable fluorescence intensities. To validate the NSC measurements, FRET spectroscopy experiments were performed with bonded dye-nanolayer films prepared under different loads (from 1.5 to 140 bar), thus creating different degrees of NSC. The results show an increase in FRET intensity (R 2 = 0.95) with the respective adhesion energy between the films, which is directly related to the degree of NSC. Hence, this work establishes FRET as an experimental technique for the measurement of NSC, and its relation to surface adhesion. Additionally, thanks to the FRET dye-nanolayer approach, the method can be employed on arbitrary surfaces. Essentially, any sufficiently transparent substrate can be functionalized with FRET compatible dyes to evaluate NSC, which represents a breakthrough in contact mechanics investigations of soft and hard solid materials.

Highly Sensitive and Selective Fluorescence and Smartphone-Based Sensor for Detection of Rutin Using Boron Nitrogen Co-doped Graphene Quantum Dots.

This research explores the fluorescence properties and photostability of boron nitrogen co-doped graphene quantum dots (BN-GQDs), evaluating their effectiveness as sensors for rutin (RU). BN-GQDs are biocompatible and exhibit notable absorbance and fluorescence characteristics, making them suitable for sensing applications. The study utilized various analytical techniques to investigate the chemical composition, structure, morphology, optical attributes, elemental composition, and particle size of BN-GQDs. Techniques included X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM). The average particle size of the BN-GQDs was determined to be approximately 3.5 ± 0.3nm. A clear correlation between the emission intensity ratio and RU concentration was identified across the range of 0.42 to 4.1μM, featuring an impressively low detection limit (LOD) of 1.23nM. The application of BN-GQDs as fluorescent probes has facilitated the development of a highly sensitive and selective RU detection method based on Förster resonance energy transfer (FRET) principles. This technique leverages emission at 465nm. Density Functional Theory (DFT) analyses confirm that FRET is the primary mechanism behind fluorescence quenching, as indicated by the energy levels of the lowest unoccupied molecular orbitals (LUMOs) of BN-GQDs and RU. The method's effectiveness has been validated by measuring RU concentrations in human serum samples, showing a recovery range between 97.8% and 103.31%. Additionally, a smartphone-based detection method utilizing BN-GQDs has been successfully implemented, achieving a detection limit (LOD) of 49nM.

Bioinspired molecular communications system for targeted drug delivery with IoBNT-based sustainable biocyber interface

This paper presents a sustainable biocyber interface approach for an intelligent targeted drug delivery system (TDDS). The proposed approach employs a bioinspired molecular communications (MC) system in which molecules are used as information carriers and a multi-input multi-output (MIMO) Forster resonance energy transfer (FRET) nanorelay to efficiently transfer therapeutic drugs from extravascular (outside blood vessels) to intravascular (within blood vessels) sites that are targeting diseased tissue. The proposed approach consists of a number of bio-nano things (BNTs) implanted inside the human intra-body nanonetwork near the diseased site. The communication among BNTs is accomplished by a sequential multistep FRET, and the nanonetwork is controlled by the Internet of Bio-Nano Thing (IoBNT) paradigm sustained by an uplink/downlink biocyber interface. The bit error rate (BER) and molecular channel capacity are utilized to evaluate the performance of the proposed approach. In addition, a Markov model decision in terms of the number of nanomachines is presented to calculate the successful probability of drug delivery and the average delay time. The numerical results show how effective the suggested method is at transmitting therapeutic medication information with an attainable bit-rate error.

FRETting about CRISPR-Cas Assays: Dual-Channel Reporting Lowers Detection Limits and Times-to-Result.

Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-Associated Protein (CRISPR-Cas) systems have evolved several mechanisms to specifically target foreign DNA. These properties have made them attractive as biosensors. The primary drawback associated with contemporary CRISPR-Cas biosensors is their weak signaling capacity, which is typically compensated for by coupling the CRISPR-Cas systems to nucleic acid amplification. An alternative strategy to improve signaling capacity is to engineer the reporter, i.e., design new signal-generating substrates for Cas proteins. Unfortunately, due to their reliance on custom synthesis, most of these engineered reporter substrates are inaccessible to many researchers. Herein, we investigate a substrate based on a fluorescein (FAM)-tetramethylrhodamine (TAMRA) Förster resonant energy-transfer (FRET) pair that functions as a seamless "drop-in" replacement for existing reporters, without the need to change any other aspect of a CRISPR-Cas12a-based assay. The reporter is readily available and employs FRET to produce two signals upon cleavage by Cas12a. The use of both signals in a ratiometric manner provides for improved assay performance and a decreased time-to-result for several CRISPR-Cas12a assays when compared to a traditional FAM-Black Hole Quencher (BHQ) quench-based reporter. We comprehensively characterize this reporter to better understand the reasons for the improved signaling capacity and benchmark it against the current standard CRISPR-Cas reporter. Finally, to showcase the real-world utility of the reporter, we employ it in a Recombinase Polymerase Amplification (RPA)-CRISPR-Cas12a DNA Endonuclease-Targeted CRISPR Trans Reporter (DETECTR) assay to detect Human papillomavirus in patient-derived samples.

A high-fidelity dual-channel fluorescence probe for benzoyl peroxide detection and toxicity early warning in food, zebrafish, and mice

Benzoyl peroxide (BPO), as a widely used organic peroxide, has attracted widespread attention from all sectors of society for its environmental hazards and potential risks to human health. Herein, we employed a Förster resonance energy transfer (FRET) strategy to construct a novel ratiometric fluorescent probe CY-DCI for BPO detection in food, zebrafish, and mice. Specifically, a hemicyanine fluorophore and a dicyanoisophorone fluorophore were connected with a piperazine group as donor and acceptor, respectively, and an olefinic unsaturated bond as the reaction site. CY-DCI has favorable selectivity and an excellent detection limit as low as 58.1 nM, and the recovery rates for real-sample detection ranged from 95.8 % to 104 %, with relative standard deviations (RSD) less than 2.58 %. To further improve its practicality, silica gel plates and test strips containing CY-DCI (0–50 μM) were developed for naked-eye detection of BPO with satisfactory results. Additionally, this novel probe was then applied for ratiometric imaging of living zebrafish and mice and showed high ratiometric imaging resolution in the green and red channels, thus demonstrating its practical application for BPO detection and toxicity early warning in food and biosystems.

Quantitative Visualization of Lipid Nanoparticle Fusion as a Function of Formulation and Process Parameters.

Lipid nanoparticles (LNPs) have proven to be promising delivery vehicles for RNA-based vaccines and therapeutics, particularly in LNP formulations containing ionizable cationic lipids that undergo protonation/deprotonation in response to buffer pH changes. These nanoparticles are typically formulated using a rapid mixing technique at low pH, followed by a return to physiological pH that triggers LNP-LNP fusion. A detailed understanding of these dynamic processes is crucial to optimize the overall performance and efficiency of LNPs. However, knowledge gaps persist regarding how particle formation mechanisms impact drug loading and delivery functions. In this work, we employ single-molecule Convex Lens-induced Confinement (CLiC) microscopy in combination with Förster resonance energy transfer (FRET) measurements to study LNP fusion dynamics in relation to various formulation parameters, including lipid concentration, buffer conditions, drug loading ratio, PEG-lipid concentrations, and ionizable lipid selection. Our results reveal a strong correlation between the measured fusion dynamics and the formulation parameters used; these findings are consistent with DLS and Cryo-TEM-based assays. These measurements offer a cost-effective method for characterizing and screening potential drug candidates and can provide additional insights into their design, with opportunities for optimization.

5-Fluoro uracil mediated transformation of surface-active ionic liquid based micellar nanoaggregates into pH-responsive vesicular nanoaggregates as promising drug delivery vehicle

Surface-active ionic liquids (SAILs) are poised as significant contenders in sustained and targeted drug delivery due to their membrane-like structures and their ability to transport drug molecules regardless of their polarity. In order to design a simple system that an encapsulate the anticancer drug and release it in a sustained manner, herein we designed vesicular nano-aggregates through synergistically interacting chemotherapeutic drug 5-Fluoro Uracil (5-FU) with the biocompatible SAILs, Choline Oleate ([Ch][Ol]) and Tetramethyl guanidine Oleate ([TMG][Ol]). The intention for designing the system is to offers less complexity and improved drug loading efficiency and targeted and sustained release. The molecular interactions have been proven by computational approach and the size of the nanoaggregates was determined using techniques such as Dynamic Light Scattering (DLS), Förster Resonance Energy Transfer (FRET) and Small-Angle Neutron Scattering (SANS). SANS fitting data and TEM images confirmed the transition of prolate ellipsoid micelles at [5-FU] = 0 mM to uni-lamellar ([5-FU] = 1 mM) and multi-lamellar vesicles ([5-FU] = 2 mM). These vesicular nano-aggregates are studied for their stability against temperature, pH-response and ionic strength of solution, revealing stability up to 60 °C, robust at physiological pH 7.4 and remain stable to exposure to Na+ and Ca2+ ions at concentrations up to 180 mM and 50 mM, respectively. The vesicular nano-aggregates ([Ch][Ol]/5-FU and [TMG][Ol]/5-FU) when exposed to physiological pH (i.e., 7.4) released 64.8 % and 61.2 % drug release whereas when the same systems were exposed to cancerous pH (5.2 and 6.7) released 95.9 % and 84.5% (pH 5.2 and 6.7) and 94.8 % and 81.2 % (pH 5.2 and 6.7) for the [Ch][Ol]/5-FU and [TMG][Ol]/5-FU systems, respectively. Results for the studied system encompasses them as a promising candidate for drug release at specific sites. The anticipated research might pave the way for the development of a biocompatible and stimuli-responsive drug carrier that would allow for the localized delivery of an anticancer drug.

Exploring the molecular binding mechanism of 6-fluoro, 4-hydroxy, 2- methyl quinoline with TiO2 nanoparticles: A spectroscopic, thermodynamic, and insights into the solvatochromic effect.

This study investigates the interaction between titanium oxide nanoparticles (TiO2 NPs) and the heterocyclic fluorophore 6-fluoro,4-hydroxy,2-methylquinoline (6-FHMQ), aiming to understand fluorescence quenching mechanisms and thermodynamic characteristics. Spectroscopic techniques including spectrofluorometry (FL) and spectrophotometry (UV-Vis) were used, with a lifetime decay (τ) of 0.18ns for 6-FHMQ measured using time correlated single photon counting (TCSPC). The interaction between 6-FHMQ and TiO2 NPs revealed a mix of static and dynamic fluorescence quenching mechanisms, with increasing quenching constants (Ksv) and a higher bimolecular quenching rate constant (Kq). The dynamic nature was highlighted by a temperature-dependent increase in binding sites from 1 to ~ 2. Spontaneous complexation was affirmed by negative change in free energy (ΔG), with negative change in enthalpy (ΔH) and a positive change in entropy (ΔS) values indicating favorable electrostatic and ionic interactions. The impact of varying TiO2 NP concentrations on 6-FHMQ absorption was analyzed using the Benesi-Hildbrand equation, with a quantum yield of 0.61 determined. By forster resonance energy transfer (FRET) theory, the proximity between 6-FHMQ and TiO2 NPs was found to be less than 70Å. Ground and excited state dipole moments of 6-FHMQ in different solvents were calculated to demonstrate solvent sensing ability and charge transfer properties. Ultimately, this study serves as a testament to the power of scientific innovation in the realms of drug delivery and tissue engineering.

Quantum Dot‐Based FRET Nanosensors for Talin‐Membrane Assembly and Mechanosensing

Understanding the mechanisms of assembly and disassembly of macromolecular structures in cells relies on solving biomolecular interactions. However, those interactions often remain unclear because tools to track molecular dynamics are not sufficiently resolved in time or space. In this study, we present a straightforward method for resolving inter‐ and intra‐molecular interactions in cell adhesive machinery, using quantum dot (QD) based Förster resonance energy transfer (FRET) nanosensors. Using a mechanosensitive protein, talin, one of the major components of focal adhesions, we are investigating the mechanosensing ability of proteins to sense and respond to mechanical stimuli. First, we quantified the distances separating talin and a giant unilamellar vesicle membrane for three talin variants. These variants differ in molecular length. Second, we investigated the mechanosensing capabilities of talin, i.e., its conformational changes due to mechanical stretching initiated by cytoskeleton contraction. Our results suggest that in early focal adhesion, talin undergoes stretching, corresponding to a decrease in the talin‐membrane distance of 2.5 nm. We demonstrate that QD‐FRET nanosensors can be applied for the sensitive quantification of mechanosensing with a sub‐nanometer accuracy.

A NIR-to-NIR non-emissive rare-earth nanoprobe that specifically lights-up inflammatory condition in vivo

Development of exquisitely selective and sensitive HClO/ClO– sensor in living system is of the utmost importance. To achieve near-infrared (NIR)-responsive detection of HClO/ClO–, a new nanoprobe (csUCNP-Cy820) is composed of the ClO–-sensitive Cy820 (energy acceptor), and NaLuF4:20%Yb,1%Tm@NaLuF4 core@shell upconversion nanoparticles (csUCNP, energy donor) capable of emitting NIR upconversion luminescence (UCL) of Tm3+ (800 nm). Through the mechanism of Förster resonance energy transfer (FRET), the UCL emission can be recovered in the presence of HClO/ClO–. The csUCNP-Cy820 nanoprobe is effectively adapted as a precise ClO– detection sensor with a low limit of detection (LoD) of 58 nmol/L in vitro. Moreover, owing to excitation and emission wavelengths both falling within the NIR region, the nanoprobe facilitates high quality imaging in mice models of peritonitis and arthritis, thereby enabling deeper penetration depth for imaging detection in vivo.

Detection of fluorescent protein mechanical switching in cellulo

The ability of cells to sense and respond to mechanical forces is critical in many physiological and pathological processes. However, determining the mechanisms by which forces affect protein function inside cells remains challenging. Motivated by invitro demonstrations of fluorescent proteins (FPs) undergoing reversible mechanical switching of fluorescence, we investigated whether force-sensitive changes in FP function could be visualized in cells. Guided by a computational model of FP mechanical switching, we develop a formalism for its detection in Förster resonance energy transfer (FRET)-based biosensors and demonstrate its occurrence in cellulo within a synthetic actin crosslinker and the mechanical linker protein vinculin. We find that in cellulo mechanical switching is reversible and altered by manipulation of cell force generation, external stiffness, and force-sensitive bond dynamics of the biosensor. This work describes a framework for assessing FP mechanical stability and provides a means of probing force-sensitive protein function inside cells.

Natural Product Graveoline Modulates Kirsten Rat Sarcoma Viral Oncogene Homologue (KRAS) Membrane Association: Insights from Advanced Spectroscopic Studies.

The KRAS gene plays a pivotal role in numerous cancers by encoding a GTPase that upon association with the plasma membrane activates the MAPK pathway, promoting cellular proliferation. In our study, we investigated small molecules that disrupt KRAS's membrane interaction, hypothesizing that such disruption could in turn inhibit mutant RAS signaling. Native mass spectrometry screening of KRAS-FMe identified compounds with a preference for interacting with the hypervariable region (HVR), and surface plasmon resonance (SPR) further refined our selection to graveoline as a compound exhibiting preferential HVR binding. Subsequent nuclear magnetic resonance (NMR) analysis showed that graveoline's interaction with KRAS depends on C-terminal O-methylation. Moreover, our findings revealed multiple interaction sites, suggesting weak engagement with the KRAS G domain. Using nanodiscs as a membrane mimetic, further characterization through NMR and Förster resonance energy transfer (FRET) studies demonstrated graveoline's ability to perturb KRAS membrane interaction in a biochemical setting. Our biophysical approach sheds light on the intricate molecular mechanisms underlying KRAS-ligand interactions, providing valuable insights into understanding the KRAS-associated pathophysiology. These findings contribute to the translational aspect of our study, offering potential avenues for further research targeting KRAS membrane association with the potential to lead to a new class of RAS therapeutics.

Polymer Nanoparticles for Preferential Delivery of Drugs Only by Exploiting the Slightly Elevated Temperature of Cancer Cells and Real-Time Monitoring of Drug Release.

Rapid proliferation and a faster rate of glycolysis in cancer cells often result in an elevated local temperature (40-43 °C) at the tumor site. Nanoparticles prepared from polymers with two lower critical solution temperatures (LCSTs) can be utilized to take advantage of this subtle temperature elevation to deliver anticancer drugs preferably to the cancer cells, thereby enhancing the overall therapeutic efficacy and reducing side effects. In this direction, we synthesized N-vinyl-2-pyrrolidone (NVP) and substituted NVP (sub-NVP: C2-NVP, C4-NVP)-based polymers with precisely controlled LCSTs by varying the ratio of NVP and sub-NVP. The first LCST (LCST1) was kept below 37 °C to promote self-assembly, drug loading, and structural stability in physiological conditions and the second LCST (LCST2) was in the range of 40-43 °C to ensure mild hyperthermia-induced drug release. Additionally, covalent attachment of tetraphenylethylene (TPE, AIEgen) resulted in aggregation-induced emission in thermoresponsive micellar nanoparticles in which TPE acted as a Förster Resonance Energy Transfer (FRET) pair with the loaded anticancer drug doxorubicin (DOX). Tracking of FRET-induced fluorescence recovery of TPE molecules was utilized to confirm the real-time thermoresponsive release of DOX from nanoparticles and eventual localization of TPE in the cytoplasm and DOX in the nucleus. In vitro cellular studies such as cytotoxicity, cellular uptake, and thermoresponsive drug release showed that the DOX-loaded polymeric nanoparticles were nontoxic to normal cells (HEK-293) but significantly more effective in cancer cells (MCF-7) at 40 °C. To our knowledge, this is the first report of preferential delivery of anticancer drugs only by exploiting the slightly elevated temperature of cancer cells.

Click generated photochromic naphthalenediimide-dithienylethene diad: Application in deciphering secret codes

Photochromic molecules with efficient fluorescence switching capability remain a core research interest among the scientific community for the application in security technologies and anti-counterfeiting measures. A dithienylethene-naphthalene diimide diad was designed and synthesized using Cu(I) catalysed click reaction between a fluorescent core substituted naphthalene diimide (cNDI) and photochromic dithienylethene (DTE) molecule, which demonstrated excellent photocyclization (ksolution = 0.0359 s−1, ksolid = 0.0122 s−1) and photocycloreversion (ksolution = 0.01737 s−1, ksolid = 0.00456 s−1) dynamics with high fluorescence quantum yield (5o ΦF = 0.39, PSS ΦF = 0.05). The fluorescence property of the molecule was switched ‘on-off’ by UV and visible light irradiation respectively via Förster resonance energy transfer (FRET) mechanism in solution state as well as in solid state, which was further corroborated with DFT studies. In view of efficient fluorescence switching behaviour and high fatigue resistance properties (25 cycles), the molecule was successfully applied in secret code encryption-decryption purposes using barcode demonstrating real-life applicability of the molecule in security technologies.

A Renal Clearable Nano-Assembly with Förster Resonance Energy Transfer Amplified Superoxide Radical and Heat Generation to Overcome Hypoxia Resistance in Phototherapeutics.

Given that type I photosensitizers (PSs) possess a good hypoxic tolerance, developing an innovative tactic to construct type I PSs is crucially important, but remains a challenge. Herein, we present a smart molecular design strategy based on the Förster resonance energy transfer (FRET) mechanism to develop a type I photodynamic therapy (PDT) agent with an encouraging amplification effect for accurate hypoxic tumor therapy. Of note, benefiting from the FRET effect, the obtained nanostructured type I PDT agent (NanoPcSZ) with boosted light-harvesting ability not only amplifies superoxide radical (O2 •-) production but also promotes heat generation upon near-infrared light irradiation. These features facilitate NanoPcSZ to realize excellent phototherapeutic response under both normal and hypoxic environments. As a result, both in vitro and in vivo experiments achieved a remarkable improvement in therapeutic efficacy via the combined effect of photothermal action and type I photoreaction. Notably, NanoPcSZ can be eliminated from organs (including the liver, lung, spleen, and kidney) apart from the tumor site and excreted through urine within 24 h of its systemic administration. In this way, the potential biotoxicity of drug accumulation can be avoided and the biosafety can be further enhanced.