Phototunable Full‐Color Emission of Cellulose‐Based Dynamic Fluorescent Materials

An iridescent chameleon‐like material that can change its colors under different circumstances is always desired in color‐on‐demand applications. Herein, a strategy based on trichromacy and the dynamically tunable fluorescence resonance energy transfer (FRET) process to design and prepare these chameleon‐like fluorescent materials is proposed. A set of trichromic (red, green, and blue), solid fluorescent materials are synthesized by covalently attaching spiropyran, fluorescein, and pyrene onto cellulose chains independently. After simply mixing them together, a full range of color is realized. The chameleon‐like nature of these materials is based on the dynamic tunable FRET process between donors (green and blue) and acceptors (red) in which the energy transfer efficiency can be finely tuned by irradiation. Ultimately, the reversible and nonlinear regulation of fluorescence properties, including color and intensity, is achieved on a timescale recognizable by the naked eye. Benefited by the excellent processability inherited from the cellulose derivatives, the as‐prepared materials are feasibly transformed into different forms. Particularly, a fluorescent ink with the complicated fluorescent input–output dependence suggests more than a proof‐of‐concept; indeed, it suggests a unique method of information encryption, security printing, and dynamic anticounterfeiting.     

Neuroendocrine Tumor‐Targeted Upconversion Nanoparticle‐Based Micelles for Simultaneous NIR‐Controlled Combination Chemotherapy and Photodynamic Therapy,and Fluorescence Imaging

Although neuroendocrine tumors (NETs) are slow growing, they are frequently metastatic at the time of discovery and no longer amenable to curative surgery, emphasizing the need for the development of other treatments. In this study, multifunctional upconversion nanoparticle (UCNP)‐based theranostic micelles are developed for NET‐targeted and near‐infrared (NIR)‐controlled combination chemotherapy and photodynamic therapy (PDT), and bioimaging. The theranostic micelle is formed by individual UCNP functionalized with light‐sensitive amphiphilic block copolymers poly(4,5‐dimethoxy‐2‐nitrobenzyl methacrylate)‐polyethylene glycol (PNBMA‐PEG) and Rose Bengal (RB) photosensitizers. A hydrophobic anticancer drug, AB3, is loaded into the micelles. The NIR‐activated UCNPs emit multiple luminescence bands, including UV, 540 nm, and 650 nm. The UV peaks overlap with the absorption peak of photocleavable hydrophobic PNBMA segments, triggering a rapid drug release due to the NIR‐induced hydrophobic‐to‐hydrophilic transition of the micelle core and thus enabling NIR‐controlled chemotherapy. RB molecules are activated via luminescence resonance energy transfer to generate ¹O₂ for NIR‐induced PDT. Meanwhile, the 650 nm emission allows for efficient fluorescence imaging. KE108, a true pansomatostatin nonapeptide, as an NET‐targeting ligand, drastically increases the tumoral uptake of the micelles. Intravenously injected AB3‐loaded UCNP‐based micelles conjugated with RB and KE108—enabling NET‐targeted combination chemotherapy and PDT—induce the best antitumor efficacy.     

CdTe Quantum Dots/Layered Double Hydroxide Ultrathin Films with Multicolor Light Emission via Layer‐by‐Layer Assembly

Quantum dots (QDs) luminescent films have broad applications in optoelectronics, solid‐state light‐emitting diodes (LEDs), and optical devices. This work reports the fabrication of multicolor‐light‐emitting ultrathin films (UTFs) with 2D architecture based on CdTe QDs and MgAl layered double hydroxide (LDH) nanosheets via the layer‐by‐layer deposition technique. The hybrid UTFs possess periodic layered structure, which is verified by X‐ray diffraction. Tunable light emission in the red‐green region is obtained by changing the particle size of QDs (CdTe‐535 QDs and CdTe‐635 QDs with green and red emision respectively), assembly cycle number, and sequence. Moreover, energy transfer between CdTe‐535 QDs and CdTe‐635 QDs occurs based on the fluorescence resonance energy transfer (FRET), which greatly enhances the fluorescence efficiency of CdTe‐635 QDs. In addition, a theoretical study based on the Förster theory and molecular dynamics (MD) simulations demonstrates that CdTe QDs/LDH UTFs exhibit superior capability of energy transfer owing to the ordered dispersion of QDs in the 2D LDH matrix, which agrees well with the experimental results. Therefore, this provides a facile approach for the design and fabrication of inorganic‐inorganic luminescent UTFs with largely enhanced luminescence efficiency as well as stability, which can be potentially applied in multicolor optical and optoelectronic devices.     

Solution‐Processable Near‐Infrared–Responsive Composite of Perovskite Nanowires and Photon‐Upconversion Nanoparticles

Organolead halide perovskites (OHPs) have shown unprecedented potentials in optoelectronics. However, the inherent large bandgap has restrained its working wavelength within 280–800 nm, while light at other regions, e.g., near‐infrared (NIR), may cause drastic thermal heating effect that goes against the duration of OHP devices, if not properly exploited. Herein, a solution processable and large‐scale synthesis of multifunctional OHP composites containing lanthanide‐doped upconversion nanoparticles (UCNPs) is reported. Upon NIR illumination, the upconverted photons from UCNPs at 520–550 nm can be efficiently absorbed by closely surrounded OHP nanowires (NWs) and photocurrent is subsequently generated. The narrow full width at half maximum of the absorption of rare earth ions (Yb³⁺ and Er³⁺) has ensured high‐selective NIR response. Lifetime characterizations have suggested that Förster resonance energy transfer with an efficiency of 28.5% should be responsible for the direct energy transfer from UCNPs to OHP NWs. The fabricated proof‐of‐concept device has showcased perfect response to NIR light at 980 and 1532 nm, which has paved new avenues for applications of such composites in remote control, distance measurement, and stealth materials.     

Hydrogen‐Bonded Two‐Component Ionic Crystals Showing Enhanced Long‐Lived Room‐Temperature Phosphorescence via TADF‐Assisted Förster Resonance Energy Transfer

Molecular room‐temperature phosphorescent (RTP) materials with long‐lived excited states have attracted widespread attention in the fields of optical imaging, displays, and sensors. However, accessing ultralong RTP systems remains challenging and examples are still limited to date. Herein, a thermally activated delayed fluorescence (TADF)‐assisted energy transfer route for the enhancement of persistent luminescence with an RTP lifetime as high as 2 s, which is higher than that of most state‐of‐the‐art RTP materials, is proposed. The energy transfer donor and acceptor species are based on the TADF and RTP molecules, which can be self‐assembled into two‐component ionic salts via hydrogen‐bonding interactions. Both theoretical and experimental studies illustrate the occurrence of effective Förster resonance energy transfer (FRET) between donor and acceptor molecules with an energy transfer efficiency as high as 76%. Moreover, the potential for application of the donor–acceptor cocrystallized materials toward information security and personal identification systems is demonstrated, benefitting from their varied afterglow lifetimes and easy recognition in the darkness. Therefore, the work described in this study not only provides a TADF‐assisted FRET strategy toward the construction of ultralong RTP, but also yields hydrogen‐bonding‐assembled two‐component molecular crystals for potential encryption and anti‐counterfeiting applications.     

Pegylated Composite Nanoparticles Containing Upconverting Phosphors and meso‐Tetraphenyl porphine (TPP) for Photodynamic Therapy

The utilization of upconverting nanophosphors (UCNP) for photodynamic therapy (PDT) has gained significant interests due to its ability to convert deep‐penetrating near‐infra red (NIR) light (i.e., 978 nm) to visible light. Previous attempts to co‐localize UCNPs with photosensitizers suffer from low photo­sensitizer loading and problems with nanoparticle aggregation. Here, the preparation of a novel composite nanoparticle formulation comprising 100 nm β?NaYF₄:Yb³⁺,Er³⁺ UCNPs, and meso‐tetraphenyl porphine (TPP) photo­sensitizer, stabilized by biocompatible poly(ethylene glycol‐block‐(dl )lactic acid) block copolymers (PEG‐b‐PLA) is presented. A photosensitizer loading of 10 wt% with respect to UCNP crystal was achieved via the Flash NanoPrecipitation (FNP) process. A sterically stabilizing PEG layer on the composite nanoparticle surface prevents nanoparticle aggregation and ensures nanoparticle stability in water, PBS buffer, and culture medium containing serum proteins, resulting in nanoparticle suitable for in vivo applications. Based on in vitro studies utilizing HeLa cervical cancer cell lines, the composite nanoparticles are shown to exhibit low dark toxicity and efficient cancer cell‐killing activity upon NIR excitation. Exposure with 134 W cm^?2 of 978 nm light for 45 min resulted in 75% HeLa cell death. This is the first quantification of the cell‐killing capabilities of the UCNP/TPP composite nanoparticles formulated for photodynamic therapy.     

Deoxyribonucleic Acid Photonic Wires with Three Primary Color Emissions for Information Encryption

DNA photonic wires (PWs) are a new type of photon delivery nanodevice and have attracted wide attention due to their excellent photon delivery ability via Förster resonance energy transfer (FRET) but are dramatically challenged in real applications. In this study, 7-amino-4-methyl-3-coumarinylacetic acid is used as a donor, Texas Red is used as an acceptor, and acridine orange is used as a bridge to intercalate DNA to facilitate the homo-FRET process, which leads to DNA PWs with high-energy transfer efficiencies (≈0.9). Notably, the newly developed DNA PWs exhibit characteristic emissions in the three primary colors, which are successively adjusted by simply changing the extent of FRET to make over 36 subtypes of fluorescence emissions. This polychroism is further applied for information encryption with high efficiency, which is a new application for DNA PWs.     

基于局域表面等离子体增强的NaYF4：Yb/Er荧光上转换及其应用

阐述了局域表面等离子体共振增强荧光上转换的相关机制,并以此为基础总结了三种调节机制和四种上转换/金属复合材料结构。具有明显增强效果的上转换/金属结构复合材料大致分为四种:掺入Au和Ag纳米颗粒的稀土掺杂基质;core/shell结构;稀土掺杂的NaYF₄靠近金属颗粒或金属纳米线所形成的gap结构;周期性金属阵列结构。最后介绍了它们在生物医学和光电子器件领域的应用进展。     

Effect of Charge Density on Energy‐Transfer Properties of Cationic Conjugated Polymers

Cationic conjugated polymers (CCPs) with different charge densities are synthesized via Suzuki polymerization. The CCPs show similar optical properties in aqueous solutions but obvious difference in fluorescence resonance energy transfer (FRET) to Texas Red‐labeled single‐stranded DNA (ssDNA‐TR). Both CCP and TR fluorescence quenching are revealed to influence the energy‐transfer process. The difference in quantum yields of CCP/ssDNA complexes highlights the importance of polymer side‐chain structures and charge density. A CCP with a high charge density and ethylene oxide as the side chain provides the highest quantum yield for CCP/ssDNA complexes, which favors FRET. TR quenching within the CCP/ssDNA complexes is predominantly determined by the CCP charge density. In contrast to the other two polymers, the CCP with low charge density provides the most‐intense polymer‐sensitized TR emission, which is due to the collective response of more optically active polymer units around TR and the minimized TR self‐quenching within the CCP/ssDNA‐TR complexes. These studies provide a new guideline for improving the signal amplification of conjugated‐polymer‐based optical sensors.     

pH‐Responsive Cyanine‐Grafted Graphene Oxide for Fluorescence Resonance Energy Transfer‐Enhanced Photothermal Therapy

Stimuli‐responsive anticancer agents are of particular interest in the field of cancer therapy. Nevertheless, so far stimuli‐responsive photothermal agents have been explored with limited success for cancer photothermal therapy (PTT). In this work, as a proof‐of‐concept, a pH‐responsive photothermal nanoconjugate for enhanced PTT efficacy, in which graphene oxide (GO) with broad NIR absorbance and effective photothermal conversion efficiency is selected as a typical model receptor of fluorescence resonance energy transfer (FRET), and grafted cyanine dye (e.g., Cypate) acts as the donor of near‐infrared fluorescence (NIRF), is reported for the first time. The conjugate of Cypate‐grafted GO exhibits different conformations in aqueous solutions at various pH, which can trigger pH‐dependent FRET effect between GO and Cypate and thus induce pH‐responsive photothermal effect of GO‐Cypate. GO‐Cypate exhibits severe cell damage owing to the enhanced photothermal effect in lysosomes, and thus generate synergistic PTT efficacy with tumor ablation upon photoirradiation after a single‐dose intravenous injection. The photothermal nanoconjugate with broad NIR absorbance as the effective receptor of FRET can smartly convert emitted NIRF energy from donor cyanine dye into additional photothermal effect for improving PTT. These results suggest that the smart nanoconjugate can act as a promising stimuli‐responsive photothermal nanoplatform for cancer therapy.     

Synthesis of Zwitterionic Water‐Soluble Oligofluorenes with Good Light‐Harvesting Ability

A new water‐soluble zwitterionic oligofluorene bearing carboxylic acid and quaternary ammonium as pendant groups (OF‐1) is synthesized and characterized. It forms aggregates by intermolecular electrostatic interactions and exhibits similar light‐harvesting ability as that of conjugated polymers. Efficient fluorescence resonance energy transfer (FRET) occurs from OF‐1 to double‐stranded DNA tagged with fluorescein (dsDNA‐F1). A photoresponsive oligofluorene (OF‐3) is also synthesized by protecting OF‐1 with 1‐(2‐nitrophenyl)ethanol. Photolysis of OF‐3 can produce OF‐1 to result in a fluorescence “turn‐on” response, thus the FRET from OF‐3 to dsDNA‐Fl can be turned on by light irradiation. OF‐3 offers the potential for remote DNA sensing.     

Quantum Yield‐Engineered Biocompatible Probes Illuminate Lung Tumor Based on Viscosity Confinement‐Mediated Antiaggregation

Low quantum yield and aggregation‐mediated quenching are two concerns for fluorescence imaging. However, there are not yet general means available for addressing these issues. Herein, a viscosity confinement‐mediated antiaggregation strategy is established to enable the improved fluorescence properties of entrapped fluorophores in dye‐encapsulation nanotechnology including quantum yield, fluorescence lifetime, and photostability. To instantiate this strategy, solid DL‐menthol (DLM) is introduced to disperse entrapped indocyanine green (ICG) fluorophores when coencapsulating DLM and ICG molecules in organic poly(lactic‐co‐glycolic acid) carriers. Depending on the robust ability of highly viscous DLM to augment the migration barrier and diminish diffusion coefficient, ICG aggregation and aggregation‐mediated quenching are demonstrated to be theoretically and experimentally inhibited, resulting in prolonged fluorescence lifetime, increased quantum yield, and facilitated radiative process. Consequently, the fluorescence imaging ability and photostability are significantly improved, enabling the in vitro, cellular‐level, and in vivo fluorescence imaging. More significantly, this solid DLM‐mediated antiaggregation strategy can act as a general method to extend to the intermolecular fluorescence resonance energy transfer (FRET) process and improve FRET efficiency via inhibiting the aggregation‐mediated quenching.     

Recent developments in fluorescence—based mincroscopy applied in biomedical sciences

1.IntroductionOverthelastfourdecades,fluorescencemicroscopyhasexperiencedatremendousinnovat-ingevolutionandisnowadaysawellestablishedtechniqueinmanyareasofbiomedicalre-search.Inaddition,fluorescencemicroscopicalimaginghasprovenanessentialtoolforstudy-ingbothcellstructureanddynamicprocessestakingplacewithinonecellorbetweenneigh-bouringcells.Thepresentshortreviewwillfocusonthemostrecentdevelopmentsinthisfieldofmicroscopy.2.ConventionalfluorescencemicroscopyTheterm“fluorescence”denotestheprope…     

Enhancement and Concurrence of Emissions from Multiple Fluorophores in a Single Emitting Layer of Micellar Nanostructures

For concurrent emission of multiple fluorophores from a single emitting layer with a highly efficient energy transfer from antenna molecules to emitting molecules by fluorescence resonance energy transfer (FRET), a paradoxical requirement in an emitting layer is necessary, that is, close placement of an emitting fluorophore and a harvesting molecule, and isolation of emitting fluorophores. Here we demonstrate how to overcome this paradox by full utilization of a micellar nanostructure consisting of a core and a corona, that is, the core is used as a place for FRET between light‐collecting donors and light‐emitting fluorophores, and the corona is used as a barrier for FRET between light‐emitting fluorophores. Enhancement of light emission from fluorophores was achieved by locating emitting fluorophores and light‐harvesting molecules at the same core of micelles. Moreover, with the same micellar nanostructure, concurrent emission of multiple fluorophores with enhanced intensity was induced by isolating them in independent micelles, the corona structure of which worked as an effective blockade for FRET.     

Poly(Acrylic Acid) Modification of Nd3+‐Sensitized Upconversion Nanophosphors for Highly Efficient UCL Imaging and pH‐Responsive Drug Delivery

In this work, a simple method is demonstrated for the synthesis of multifunctional core–shell nanoparticles NaYF₄:Yb,Er@NaYF₄:Yb@NaNdF₄:Yb@NaYF₄:Yb@PAA (labeled as Er@Y@Nd@Y@PAA or UCNP@PAA), which contain a highly effective 808‐nm‐to‐visible UCNP core and a thin shell of poly(acrylic acid) (PAA) to achieve upconversion bioimaging and pH‐sensitive anticancer chemotherapy simultaneously. The core–shell Nd³⁺‐sensitized UCNPs are optimized by varying the shell number, core size, and host lattices. The final optimized Er@Y@Nd@Y nanoparticle composition shows a significantly improved upconversion luminescence intensity, that is, 12.8 times higher than Er@Y@Nd nanoparticles. After coating the nanocomposites with a thin layer of PAA, the resulting UCNP@PAA nanocomposite perform well as a pH‐responsive nanocarrier and show clear advantages over UCNP@mSiO₂, which are evidenced by in vitro/in vivo experiments. Histological analysis also reveals that no pathological changes or inflammatory responses occur in the heart, lungs, kidneys, liver, and spleen. In summary, this study presents a major step forward towards a new therapeutic and diagnostic treatment of tumors by using 808‐nm excited UCNPs to replace the traditional 980‐nm excitation.     

Removing the Obstacle of Dye‐Sensitized Upconversion Luminescence in Aqueous Phase to Achieve High‐Contrast Deep Imaging In Vivo

Although upconversion nanoparticles (UCNPs) have drawn increasing attention for their unique photophysical characteristics, they suffer from a bottleneck of low luminescence efficiency due to the poor absorption coefficient of Ln³⁺. Dye sensitization has provided thousands‐fold enhancement of upconversion luminescence (UCL) in organic solvents because of the remarkably improved light absorption ability, but the sensitization of UCL in aqueous phase is only less than 20 folds by far, with unknown restrictive factors. Herein, the aggregation‐caused quenching (ACQ) of dyes is revealed as the most important reason limiting dye sensitization in aqueous phase, and the problem is circumvented through delicately modulating the physical properties of dyes and their assembly manner with UCNPs. By further alleviating energy back transfer (EBT) from Ln³⁺ to dyes, more than 600‐fold enhancement of UCL is achieved in aqueous phase. The as‐obtained dyes modified UCNPs show good biocompatibility and high signal contrast when applied for deep in vivo imaging.     

Simultaneous and Dual Emissive Imaging by Micro‐Contact Printing on the Surface of Electrostatically Assembled Water‐Soluble Poly(p‐phenylene) Using FRET

Poly{[2,5‐bis(3‐sulfonatobutoxy)‐1,4‐phenylene sodium salt]‐alt‐(1,4‐phenylene)}, which is an anionically charged, water‐soluble poly(para‐phenylene) derivative with aldehyde groups at both chain ends, is prepared via the Suzuki coupling reaction in order to develop a FRET energy donor, while simultaneously dual‐fluorescence‐patterning the protein. Regardless of the end‐capping, the synthesized polymer exhibits a good solubility in water with an absorption maximum at 338 nm and a photoluminescence maximum at 417 nm, similar to those of the the end‐capped polymer. The emission spectrum of the polymer overlaps the absorption spectrum of fluorescein, and therefore, the polymer can be used as an energy donor with fluorescein as the energy acceptor in the FRET mechanism. This polymer design not only takes advantage of the introduction of biotin at both chain ends (through a reaction with the aldehyde end groups) to realize the facile interaction with streptavidin, but also brings into play the electrostatic features of the anionic sulfonate groups to fabricate an electrostatic self‐assembly with polycation for the pattern substrate. The micropattern of fluorescein‐labeled streptavidin is fabricated on the polymer‐coated substrate through micro‐contact printing using a polydimethylsiloxane mold. As a result, the polymer substrate exhibits a dual fluorescence micropattern, which results from the blue emission color from the energy donor and the FRET‐amplified green emission from the energy acceptor. The high‐resolution patterning is carried out for the application of multiplexing by simultaneously imaging the patterned green‐emitting fluorescein by FRET and the surrounding blue‐emitting polymer according to an optical detection scheme.     

Hyperbranched Polyglycerol‐Doped Mesoporous Silica Nanoparticles for One‐ and Two‐Photon Activated Photodynamic Therapy

Two‐photon activated photodynamic therapy (TPA‐PDT) is a recently developed technique that shows a potential for medical application. In contrast to traditional one‐photon activated PDT, TPA‐PDT can increase the treatment depth and decrease the damage to healthy tissue by using a near‐infrared two‐photon laser. However, this technique also suffers from the fact that approved photosensitive drugs have a low two‐photon absorption cross section. In this study, it is demonstrate that doped polyglycerol mesoporous silica nanoparticles can carry a photosensitizer, Rose bengal, and can be applied in one‐ and two‐photon PDT. TPA dye‐doped mesoporous silica nanoparticles have been synthesized using a surfactant‐free route, which can be considered a TPA‐PDT platform after loading normal photosensitive drugs. The doped TPA dyes in the silica nanoparticles can transfer energy to the loading drugs via an intraparticle fluorescence resonance energy transfer (FRET) mechanism. The fluorescence lifetime and confocal laser scanning microscopy (CLSM) images obtained under different conditions demonstrated a FRET effect through both one‐ and two‐photon activated modes. The results of cytotoxicity experiments proved that this TPA‐PDT system could induce cellular apoptosis under one‐ or two‐photon irradiation. This system in principle extends the application range of TPA‐PDT.     

Enhancement of Aggregation‐Induced Emission in Dye‐Encapsulating Polymeric Micelles for Bioimaging

Three amphiphilic block copolymers are employed to form polymeric micelles and function as nanocarriers to disperse hydrophobic aggregation‐induced emission (AIE) dyes, 1,1,2,3,4,5‐hexaphenylsilole (HPS) and/or bis(4‐(N‐(1‐naphthyl) phenylamino)‐phenyl)fumaronitrile (NPAFN), into aqueous solution for biological studies. Compared to their virtually non‐emissive properties in organic solutions, the fluorescence intensity of these AIE dyes has increased significantly due to the spatial confinement that restricts intramolecular rotation of these dyes and their better compatibility in the hydrophobic core of polymeric micelles. The effect of the chemical structure of micelle cores on the photophysical properties of AIE dyes are investigated, and the fluorescence resonance energy transfer (FRET) from the green‐emitting donor (HPS) to the red‐emitting acceptor (NPAFN) is explored by co‐encapsulating this FRET pair in the same micelle core. The highest fluorescence quantum yield (～62%) could be achieved by encapsulating HPS aggregates in the micelles. Efficient energy transfer (>99%) and high amplification of emission (as high as 8 times) from the NPAFN acceptor could also be achieved by spatially confining the HPS/NPAFN FRET pair in the hydrophobic core of polymeric micelles. These micelles could be successfully internalized into the RAW 264.7 cells to demonstrate high‐quality fluorescent images and cell viability due to improved quantum yield and reduced cytotoxicity.     

Multicomponent Organic Nanoparticles for Fluorescence Studies in Biological Systems

The formation of dual‐component organic nanoparticles by a modified emulsion‐templated freeze‐drying approach leads to aqueous nanosuspensions showing fluorescence (Förster) resonance energy transfer (FRET) from within a distribution of single nanoparticles. The combination of both FRET dyes within dual‐component nanoparticles (<200 nm) allows the spatial and physical monitoring of the particles, as the FRET signal is lost on dissolution and breakdown of the nanoparticles. The monitoring of accumulation by Caco‐2 cells and macrophages shows very limited internalization within the non‐phagocytic cells. Conservation of FRET within the macrophages confirms extensive whole‐particle internalization. The cellular permeability through Caco‐2 monolayers is also assessed and movement of intact dual‐component particles is observed, suggesting a mechanism for enhanced pharmacokinetics in vivo.