Ultralong Phosphorescence of Water‐Soluble Organic Nanoparticles for In Vivo Afterglow Imaging

Afterglow or persistent luminescence eliminates the need for light excitation and thus circumvents the issue of autofluorescence, holding promise for molecular imaging. However, current persistent luminescence agents are rare and limited to inorganic nanoparticles. This study reports the design principle, synthesis, and proof‐of‐concept application of organic semiconducting nanoparticles (OSNs) with ultralong phosphorescence for in vivo afterglow imaging. The design principle leverages the formation of aggregates through a top‐down nanoparticle formulation to greatly stabilize the triplet excited states of a phosphorescent molecule. This prolongs the particle luminesce to the timescale that can be detected by the commercial whole‐animal imaging system after removal of external light source. Such ultralong phosphorescent of OSNs is inert to oxygen and can be repeatedly activated, permitting imaging of lymph nodes in living mice with a high signal‐to‐noise ratio. This study not only introduces the first category of water‐soluble ultralong phosphorescence organic nanoparticles but also reveals a universal design principle to prolong the lifetime of phosphorescent molecules to the level that can be effective for molecular imaging.     

A Self-Assembled Plasmonic Substrate for Enhanced Fluorescence Resonance Energy Transfer

Fluorescence resonance energy transfer (FRET) has found widespread uses in biosensing, molecular imaging, and light harvesting. Plasmonic metal nanostructures offer the possibility of engineering photonic environment of specific fluorophores to enhance the FRET efficiency. However, the potential of plasmonic nanostructures to enable tailored FRET enhancement on planar substrates remains largely unrealized, which are of considerable interest for high-performance on-surface bioassays and photovoltaics. The main challenge lies in the necessitated concurrent control over the spectral properties of plasmonic substrates to match that of fluorophores and the fluorophore–substrate spacing. Here, a self-assembled plasmonic substrate based on polydopamine (PDA)-coated plasmonic nanocrystals is developed to effectively address this challenge. The PDA coating not only drives interfacial self-assembly of the nanocrystals to form closely packed arrays with customized optical properties, but also can serve as a tailored nanoscale spacer between the fluorophores and plasmonic nanocrystals, which collectively lead to optimized fluorescence enhancement. The biocompatible plasmonic substrate that allows convenient bioconjugation imparted by PDA has afforded improved FRET efficiency in DNA microarray assay and FRET imaging of live cells. It is envisioned that the self-assembled plasmonic substrates can be readily integrated into fluorescence-based platforms for diverse biomedical and photoconversion applications.     

Coloring Afterglow Nanoparticles for High-Contrast Time-Gating-Free Multiplex Luminescence Imaging

Afterglow nanoparticles (AGNPs) possessing inherently long lifetime with tailorable emission colors and uniform size have long been sought due to their time-gating-free high-contrast multiplexing imaging. Herein, via a straightforward template method, it is reported that such multicolor AGNPs can be accomplished. The resultant AGNPs exhibit a series of tunable afterglow emissions, including blue, yellow, green, and white. These multicolor AGNPs are found to be highly bright, enabling them to perform high-contrast multichannel afterglow imaging in vitro and in vivo without the use of any complicated time-gating algorithms or systems, which existing tools are unable to do.     

Hyperbranched Conjugated Polyelectrolyte for Dual‐modality Fluorescence and Magnetic Resonance Cancer Imaging

Herein is reported the synthesis of gadolinium ion (Gd(III))‐chelated hyperbranched conjugated polyelectrolyte (HCPE‐Gd) and its application in fluorescence and magnetic resonance (MR) dual imaging in live animals. The synthesized HCPE‐Gd forms nanospheres with an average diameter of ～42 nm measured by laser light scattering and a quantum yield of 10% in aqueous solution. The absorption spectrum of HCPE‐Gd has two maxima at 318 and 417 nm, and its photoluminescence maximum centers at 591 nm. Confocal laser scanning microscopy studies indicate that the HCPE‐Gd is internalized in MCF‐7 cancer cell cytoplasm with good photostability and low cytotoxicity. Further fluorescence and MR imaging studies on hepatoma H₂₂ tumor‐bearing mouse model reveal that HCPE‐Gd can serve as an efficient optical/MR dual‐modal imaging nanoprobe for in vivo cancer diagnosis.     

Efficient Radioisotope Energy Transfer by Gold Nanoclusters for Molecular Imaging

Beta‐emitting isotopes Fluorine‐18 and Yttrium‐90 are tested for their potential to stimulate gold nanoclusters conjugated with blood serum proteins (AuNCs). AuNCs excited by either medical radioisotope are found to be highly effective ionizing radiation energy transfer mediators, suitable for in vivo optical imaging. AuNCs synthesized with protein templates convert beta‐decaying radioisotope energy into tissue‐penetrating optical signals between 620 and 800 nm. Optical signals are not detected from AuNCs incubated with Technetium‐99m, a pure gamma emitter that is used as a control. Optical emission from AuNCs is not proportional to Cerenkov radiation, indicating that the energy transfer between the radionuclide and AuNC is only partially mediated by Cerenkov photons. A direct Coulombic interaction is proposed as a novel and significant mechanism of energy transfer between decaying radionuclides and AuNCs.     

Optimizing Energy Transfer in Nanostructures Enables In Vivo Cancer Lesion Tracking via Near-Infrared Excited Hypoxia Imaging

To explore highly sensitive and low-toxicity techniques for tracking and evaluation of non-small-cell lung cancer (NSCLC), one of the most mortal tumors in the world, it is utterly imperative for doctors to select the appropriate treatment strategies. Herein, developing near-infrared (NIR) excited nanosensors, in which the donor and acceptor pairs within a biological metal–organic framework (bio-MOF) matrix are precisely controlled to rationalize upconversion Förster resonance energy transfer (FRET), is suggested for detecting the O₂ concentration inside tumors with reduced signal disturbance and health detriment. Under NIR excitation, as-fabricated core/satellite nanosensors exhibit much improved FRET efficiency and reversible hypoxic response with high sensitivity, which are effective both in vitro and in vivo (zebrafish) for cycling normoxia–hypoxia imaging. Significantly, combined with a reliable preclinical genetically engineered murine model, such nanosensors successfully realize tracking of in vivo NSCLC lesions upon clear and gradient hypoxia signals without apparent long-term biotoxicity, illustrating their exciting potential for efficient NSCLC evaluation and prognosis.     

Y2O2S:0.03Eu,0.03Ti的长余辉特性及Ti向Eu3+的余辉传能机制

采用高温还原法合成了Eu，Ti共激活橙红色Y2O2S长余辉发光材料，并测量了Y2O2S：0．03Eu,0．03Ti磷光体的荧光光谱，余辉分辨和余辉衰减曲线谱．实验结果表明，Y2O2S：0．03Eu,0．03Ti磷光体的发射谱由一系列Eu^3＋离子内部能级跃迁的尖峰组成；余辉分辨谱则不同，由一个主峰位于565nm的宽发射带和一系列波长范围位于500nm以上的窄发射带两种峰形组成，可分别归为Ti离子的宽带余辉发射和三价Eu^3＋的线状余辉发射,分析认为，样品中存在Ti余辉发射向Eu^3＋内部能级间产生选择性的余辉传能机制，从而导致Y2O2S：0．03Ti，0．03Eu磷光体中同时出现两种发光中心离子的余辉分辨谱现象．     

Near-Infrared AIE Dots with Chemiluminescence for Deep-Tissue Imaging

Near-infrared (NIR) chemiluminescence (CL) emission is highly favorable for deep-tissue imaging, but chemically conjugated NIR CL emitters with the aggregation-induced emission (AIE) property for biotechnology are seldom reported. Herein, an AIE-active NIR CL emitter, TBL, is synthesized by conjugating luminol unit with electron-accepting benzothiadiazole and an electron-donating triphenylamine, and subsequently TBL dots are prepared by using F127 as the surfactant. The CL emission of TBL dots can last continuously for over 60 min and can be employed for quantitative (in vitro) and qualitative (in vivo) detection of ¹O₂. Strikingly, the NIR CL emission can penetrate through tissues with a total thickness of over 3 cm, exhibiting significantly better performance than NIR fluorescence emission and blue CL emission. Moreover, the successful differentiation of tumor and normal tissues by TBL-based CL imaging in vivo also paves the way for CL-guided cancer diagnosis and surgery.     

Biodegradable Polysilsesquioxane Nanoparticles as Efficient Contrast Agents for Magnetic Resonance Imaging

Polysilsesquioxane (PSQ) nanoparticles are crosslinked homopolymers formed by condensation of functionalized trialkoxysilanes, and provide an interesting platform for developing biologically and biomedically relevant nanomaterials. In this work, the design and synthesis of biodegradable PSQ particles with extremely high payloads of paramagnetic Gd(III) centers is explored, for use as efficient contrast agents for magnetic resonance imaging (MRI). Two new bis(trialkoxysilyl) derivatives of Gd(III) diethylenetriamine pentaacetate (Gd‐DTPA) containing disulfide linkages are synthesized and used to form biodegradable Gd‐PSQ particles by base‐catalyzed condensation reactions in reverse microemulsions. The Gd‐PSQ particles, PSQ‐ 1 and PSQ‐ 2 , carry 53.8 wt% and 49.3 wt% of Gd‐DTPA derivatives, respectively. In addition, the surface carboxy groups on the PSQ‐ 2 particles can be modified with polyethylene glycol (PEG) and the anisamide (AA) ligand to enhance biocompatibility and cell uptake, respectively. The Gd‐PSQ particles are readily degradable to release the constituent Gd(III) chelates in the presence of endogenous reducing agents such as cysteine and glutathione. The MR relaxivities of the Gd‐PSQ particles are determined using a 3T MR scanner, with r₁ values ranging from 5.9 to 17.8 mMs^?1 on a per‐Gd basis. Finally, the high sensitivity of the Gd‐PSQ particles as T₁‐weighted MR contrast agents is demonstrated with in vitro MR imaging of human lung and pancreatic cancer cells. The enhanced efficiency of the anisamide‐functionalized PSQ‐ 2 particles as a contrast agent is corroborated by both confocal laser scanning microscopy imaging and ICP‐MS analysis of Gd content in vitro.     

Water‐Dispersible,pH‐Stable and Highly‐Luminescent Organic Dye Nanoparticles with Amplified Emissions for In Vitro and In Vivo Bioimaging

A new strategy is presented for using doped small‐molecule organic nanoparticles (NPs) to achieve high‐performance fluorescent probes with strong brightness, large Stokes shifts and tunable emissions for in vitro and in vivo imaging. The host organic NPs are used not only as carriers to encapsulate different doped dyes, but also as fluorescence resonance energy transfer donors to couple with the doped dyes (as acceptors) to achieve multicolor luminescence with amplified emissions (AE). The resulting optimum green emitting NPs show high brightness with quantum yield (QY) of up to 45% and AE of 12 times; and the red emitting NPs show QY of 14% and AE of 10 times. These highly‐luminescent doped NPs can be further surface modified with poly(maleic anhydride‐alt‐1‐octadecene)‐polyethylene glycol (C18PMH‐PEG), endowing them with excellent water dispersibility and robust stability in various bio‐environments covering wide pH values from 2 to 10. In this study, cytotoxicity studies and folic acid targeted cellular imaging of these multicolor probes are carried out to demonstrate their potential for in vitro imaging. On this basis, applications of the NP probes in in vivo and ex vivo imaging are also investigated. Intense fluorescent signals of the doped NPs are distinctly, selectively and spatially resolved in tumor sites with high sensitivity, due to the preferential accumulation of the NPs in tumor sites through the passive enhanced permeability and retention effect. The results clearly indicate that these doped NPs are promising fluorescent probes for biomedical applications.     

Plasmon Resonance Energy Transfer: Coupling between Chromophore Molecules and Metallic Nanoparticles

Plasmon resonance energy transfer (PRET) from a single metallic nanoparticle to the molecules adsorbed on its surface has attracted more and more attentions in recent years. Here, a molecular beacon (MB)‐regulated PRET coupling system composed of gold nanoparticles (GNPs) and chromophore molecules has been designed to study the influence of PRET effect on the scattering spectra of GNPs. In this system, the chromophore molecules are tagged to the 5′‐end of MB, which can form a hairpin structure and modified on the surface of GNPs by its thiol‐labeled 3′‐end. Therefore, the distance between GNPs and chromophore molecules can be adjusted through the open and close of the MB loop. From the peak shift, the PRET interactions of different GNPs‐chromophore molecules coupling pairs have been calculated by discrete dipole approximation and the fitting results match well with the experimental data. Therefore, the proposed system has been successfully applied for the analysis of PRET situation between various metallic nanoparticles and chromophore molecules, and provides a useful tool for the potential application in screening the PRET‐based nanoplasmonic sensors.     

Ultrasmall Nanoplatforms as Calcium‐Responsive Contrast Agents for Magnetic Resonance Imaging

The preparation of ultrasmall and rigid platforms (USRPs) that are covalently coupled to macrocycle‐based, calcium‐responsive/smart contrast agents (SCAs), and the initial in vitro and in vivo validation of the resulting nanosized probes (SCA‐USRPs) by means of magnetic resonance imaging (MRI) is reported. The synthetic procedure is robust, allowing preparation of the SCA‐USRPs on a multigram scale. The resulting platforms display the desired MRI activity—i.e., longitudinal relaxivity increases almost twice at 7 T magnetic field strength upon saturation with Ca²⁺. Cell viability is probed with the MTT assay using HEK‐293 cells, which show good tolerance for lower contrast agent concentrations over longer periods of time. On intravenous administration of SCA‐USRPs in living mice, MRI studies indicate their rapid accumulation in the renal pelvis and parenchyma. Importantly, the MRI signal increases in both kidney compartments when CaCl₂ is also administrated. Laser‐induced breakdown spectroscopy experiments confirm accumulation of SCA‐USRPs in the renal cortex. To the best of our knowledge, these are the first studies which demonstrate calcium‐sensitive MRI signal changes in vivo. Continuing contrast agent and MRI protocol optimizations should lead to wider application of these responsive probes and development of superior functional methods for monitoring calcium‐dependent physiological and pathological processes in a dynamic manner.     

Enhancing Photodynamic Therapy through Resonance Energy Transfer Constructed Near‐Infrared Photosensitized Nanoparticles

Photodynamic therapy (PDT) is an important cancer treatment modality due to its minimally invasive nature. However, the efficiency of existing PDT drug molecules in the deep‐tissue‐penetrable near‐infrared (NIR) region has been the major hurdle that has hindered further development and clinical usage of PDT. Thus, herein a strategy is presented to utilize a resonance energy transfer (RET) mechanism to construct a novel dyad photosensitizer which is able to dramatically boost NIR photon utility and enhance singlet oxygen generation. In this work, the energy donor moiety (distyryl‐BODIPY) is connected to a photosensitizer (i.e., diiodo‐distyryl‐BODIPY) to form a dyad molecule ( RET‐BDP ). The resulting RET‐BDP shows significantly enhanced absorption and singlet oxygen efficiency relative to that of the acceptor moiety of the photosensitizer alone in the NIR range. After being encapsulated with biodegradable copolymer pluronic F‐127‐folic acid (F‐127‐FA), RET‐BDP molecules can form uniform and small organic nanoparticles that are water soluble and tumor targetable. Used in conjunction with an exceptionally low‐power NIR LED light irradiation (10 mW cm^?2), these nanoparticles show superior tumor‐targeted therapeutic PDT effects against cancer cells both in vitro and in vivo relative to unmodified photosensitizers. This study offers a new method to expand the options for designing NIR‐absorbing photosensitizers for future clinical cancer treatments.     

Surface‐Tunable Bioluminescence Resonance Energy Transfer via Geometry‐Controlled ZnO Nanorod Coordination

The use of ZnO nanorods (NRs) as an effective coordinator and biosensing platform to create bioluminescence resonance energy transfer (BRET) is reported. Herein, a hydrothermal approach is applied to obtain morphologically controlled ZnO NRs, which are directly bound to luciferase (Luc) and carboxy‐modified quantum dot (QD) acting as a donor–acceptor pair for BRET. BRET efficiency varies significantly with the geometry of ZnO NRs, which modulates the coordination between hexahistidine‐tagged Luc (Luc‐His₆) and QD, owing to the combined effect of the total surface area consisting of (001) and (100) planes and their surface polarities. Unlike typical QD–BRET reactions with metal ions (e.g., zinc ions), a geometry‐controlled ZnO NR platform can facilitate the design of surface‐initiated BRET sensors without being supplemented by copious metal ions: the geometry‐controlled ZnO NR platform can therefore pave the way for nanostructure‐based biosensors with enhanced analytical performance.     

Upconversion Luminescence Resonance Energy Transfer (LRET)‐Based Biosensor for Rapid and Ultrasensitive Detection of Avian Influenza Virus H7 Subtype

Avian influenza viruses (AIV) with good adaptation and various mutations have threatened both human and animals’ health. The H7 subtypes have the potential to cause pandemic threats to human health due to the highly pathogenic characteristics. Therefore, it is quite urgent to develop a novel biosensor for rapid and sensitive detection of H7 subtypes. In this work, a biosensor based on luminescence resonance energy transfer (LRET) from BaGdF₅:Yb/Er upconversion nanoparticles (UCNPs) to gold nanoparticles (AuNPs) has been developed for rapid and sensitive H7 subtypes detection. The amino modified capture oligonucleotide probes are covalently linked to poly(ethylenimine) (PEI) modified BaGdF₅:Yb/Er UCNPs. The thiol modified oligonucleotides with H7 hemagglutinin gene sequence are conjugated to surfaces of AuNPs. The hybridization process between complementary strands of H7 Hemagglutinin gene and its probe brings the energy donor and acceptor into close proximity, leading to the quenching of fluorescence of UCNPs. A linear response is obtained ranging from 10 pm to 10 nm and the limit of detection (LOD) is around 7 pm with detection time around 2 hours. This biosensor is expected to be a valuable diagnostic tool for rapid and sensitive detection of AIV.     

Probing Lipid Coating Dynamics of Quantum Dot Core Micelles via Förster Resonance Energy Transfer

Lipid coated nanocrystal assemblies are among the most extensively investigated nanoparticle platforms for biomedical imaging and therapeutic purposes. However, very few efforts have been addressed to the lipid coating exchange dynamics in such systems, which is key to our understanding of the nanoparticles' coating stability and their interactions with the environment. Here, we apply the Förster resonance energy transfer (FRET) from quantum dot (QD) core to Cy5.5 dye labeled lipids at the surface to monitor the lipid exchange dynamics in situ and to study its dependence on concentration, temperature and solvent. A kinetic model is developed to describe the experimental data, allowing the rate constants and the activation energy for lipid exchange to be determined. The activation energy for lipid exchange on QD micelles is 155 kJ/mol in saline environment and 130 kJ/mol in pure water. The findings presented here provide basic knowledge on these self‐assembled structures and contribute to understanding their performance and to further design of nanomedicine.     

In Situ Investigation on the Protein Corona Formation of Quantum Dots by Using Fluorescence Resonance Energy Transfer

A fundamental understanding of nanoparticle–protein corona and its interactions with biological systems is essential for future application of engineered nanomaterials. In this work, fluorescence resonance energy transfer (FRET) is employed for studying the protein adsorption behavior of nanoparticles. The adsorption of human serum albumin (HSA) onto the surface of InP@ZnS quantum dots (QDs) with different chirality (d ‐ and l ‐penicillamine) shows strong discernible differences in the binding behaviors including affinity and adsorption orientation that are obtained upon quantitative analysis of FRET data. Circular dichroism spectroscopy further confirms the differences in the conformational changes of HSA upon interaction with d ‐ and l ‐chiral QD surfaces. Consequently, the formed protein corona on chiral surfaces may affect their following biological interactions, such as possible protein exchange with serum proteins plasma as well as cellular interactions. These results vividly illustrate the potential of the FRET method as a simple yet versatile platform for quantitatively investigating biological interactions of nanoparticles.     

高温多元醇法制备超顺磁CoFe2O4纳米颗粒磁共振造影剂

以FeCl₃·6H₂O、CoCl₂·6H₂O和HOOC-PEG-COOH为反应物, 利用高温多元醇法制备了核心粒径为5~10nm的超顺磁CoFe₂O₄纳米颗粒, 样品在水溶液中具有良好分散性. 通过改变修饰剂的种类和用量、反应温度及反应时间可以对纳米颗粒的尺寸、水中分散性及磁性能产生影响. 研究表明：选用带有强极性基团的修饰剂, 增加修饰剂的用量, 提高反应温度和延长反应时间, 可以增大颗粒的尺寸, 改善颗粒的分散性, 窄化粒径分布. 实验获得的最佳生长条件为：金属盐总量与修饰剂质量比为1∶10, 在210~220℃之间反应2h. 磁性能研究表明所得样品在室温下具有超顺磁性, 其饱和磁化强度与尺寸有关.     

Magnetically Engineered Semiconductor Quantum Dots as Multimodal Imaging Probes

Light‐emitting semiconductor quantum dots (QDs) combined with magnetic resonance imaging contrast agents within a single nanoparticle platform are considered to perform as multimodal imaging probes in biomedical research and related clinical applications. The principles of their rational design are outlined and contemporary synthetic strategies are reviewed (heterocrystalline growth; co‐encapsulation or assembly of preformed QDs and magnetic nanoparticles; conjugation of magnetic chelates onto QDs; and doping of QDs with transition metal ions), identifying the strengths and weaknesses of different approaches. Some of the opportunities and benefits that arise through in vivo imaging using these dual‐mode probes are highlighted where tumor location and delineation is demonstrated in both MRI and fluorescence modality. Work on the toxicological assessments of QD/magnetic nanoparticles is also reviewed, along with progress in reducing their toxicological side effects for eventual clinical use. The review concludes with an outlook for future biomedical imaging and the identification of key challenges in reaching clinical applications.