Self‐Limiting Growth Nanoscale Coordination Polymers for Fluorescence and Magnetic Resonance Dual‐Modality Imaging

The size and shape of coordination polymers (CPs) are often tuned by external factors including reaction temperature, reaction time, precursor ratio, auxiliary ligand, and surfactant. Here, a self‐limiting growth of uniform nanoscale CPs (NCPs) spheres with Gd³⁺ and Ru[4,4′‐(COOH)₂ bipyridyl(bpy)]₃²⁺ ( L_Ru ) as precursors is reported. Sexadentate L_Ru and nine‐coordinating Gd³⁺ play key roles in the formation of the NCPs via a simple and robust self‐limiting procedure. Therefore, the formation of NCP spheres is almost unaffected in the reaction temperature of 100–160 °C for 1–6 h. Moreover, no auxiliary ligand or surfactant is required, whereas high yield and simple procedure are obtained. The red fluorescence of L_Ru and high longitudinal relaxivity of Gd³⁺ remain in the NCPs, which are therefore examined as fluorescence‐magnetic resonance (MR) dual‐modality imaging probes. The structural merits of the NCPs enable high MR contrast efficiency. Red emission avoids the auto‐fluorescence and light scattering from tissues and realizes low‐background imaging. The low toxicity and background, and high imaging efficiency of the NCPs are confirmed using HepG2 cells, zebrafish, and tumor‐bearing mice as models.     

Conjugated Polymer Based Nanoparticles as Dual‐Modal Probes for Targeted In Vivo Fluorescence and Magnetic Resonance Imaging

A facile strategy is developed to synthesize dual‐modal fluorescent‐magnetic nanoparticles (NPs) with surface folic acid by co‐encapsulation of a far‐red/near‐infrared (FR/NIR)‐emissive conjugated polymer (PFVBT) and lipid‐coated iron oxides (IOs) into a mixture of poly(lactic‐co‐glycolic‐acid)‐poly(ethylene glycol)‐folate (PLGA‐PEG‐FOL) and PLGA. The obtained NPs exhibit superparamagnetic properties and high fluorescence, which indicates that the lipid coated on IOs is effective at separating the conjugated polymer from IOs to minimize fluorescence quenching. These NPs are spherical in shape with an average diameter of ≈180 nm in water, as determined by laser light scattering. In vitro studies reveal that these dual‐modal NPs can serve as an effective fluorescent probe to achieve targeted imaging of MCF‐7 breast cancer cells without obvious cytotoxicity. In vivo fluorescence and magnetic resonance imaging results suggest that the NPs are able to preferentially accumulate in tumor tissues to allow dual‐modal detection of tumors in a living body. This demonstrates the potential of conjugated polymer based dual‐modal nanoprobes for versatile in vitro and in vivo applications in future.     

Citrate‐Based Tannin‐Bridged Bone Composites for Lumbar Fusion

Conventional bone composites consistently fail to mimic the chemical composition and integrated organic/inorganic structure of natural bone, lacking sufficient mechanics as well as inherent osteoconductivity and osteoinductivity. Through a facile surface coating process, the strong adhesive, tannic acid (TA), is adhered to the surface of the natural bone component, hydroxyapatite (HA), with and without the immobilization of in situ formed silver nanoparticles. Residual functional groups available on the immobilized TA substituents are subsequently covalently linked to the citrate‐based biodegradable polymer, poly(octamethylene citrate) (POC), effectively bridging the organic and inorganic phases. Due to the synergistic effects of the tannin and citrate components, the obtained citrate‐based tannin‐bridged bone composites (CTBCs) exhibit vastly improved compression strengths up to 323.0 ± 21.3 MPa compared to 229.9 ± 15.6 MPa for POC‐HA, and possess tunable degradation profiles, enhanced biomineralization performance, favorable biocompatibility, increased cell adhesion and proliferation, as well as considerable antimicrobial activity. In vivo study of porous CTBCs using a lumbar fusion model further confirms CTBCs' osteoconductivity and osteoinductivity, promoting bone regeneration. CTBCs possess great potential for bone regeneration applications while the immobilized TA additionally preserves surface bioconjugation sites to further tailor the bioactivity of CTBCs.     

In Vivo Photoacoustic Imaging of Livers Using Biodegradable Hyaluronic Acid‐Conjugated Silica Nanoparticles

The diagnosis of liver diseases is generally carried out via ultrasound imaging, computed tomography, and magnetic resonance imaging. The emerging photoacoustic imaging is an attractive alternative to diagnose even early stage of liver diseases providing high‐resolution anatomical and functional information in deep tissue noninvasively. However, the liver has insufficient photoacoustic contrast due to low optical absorbance in the near‐infrared windows. Here, a new hyaluronate–silica nanoparticle (HA–SiNP) conjugate for liver‐specific delivery and imaging for the diagnosis of liver diseases is developed. The HA–SiNP conjugates show high liver‐specific targeting efficiency, strong optical absorbance near‐infrared windows, excellent biocompatibility, and biodegradability. The liver‐specific targeting efficiency is verified by in vitro cellular uptake test, and in vivo and ex vivo photoacoustic imaging. In vivo photoacoustic imaging shows that photoacoustic amplitude in the liver injected with HA–SiNP conjugates is 4.4 times higher than that of the liver injected with SiNP. The biocompatibility and biodegradability of HA–SiNP conjugates are verified by cell viability test, optical spectrum analysis of urine, and inductively coupled plasma‐mass spectroscopy (ICP‐MS) analysis. Taken together, HA–SiNP conjugates may be developed as a promising liver targeted photoacoustic imaging contrast agent and liver‐targeted drug delivery agent.     

A Versatile Nanotheranostic Agent for Efficient Dual‐Mode Imaging Guided Synergistic Chemo‐Thermal Tumor Therapy

The integration of efficient imaging for diagnosis and synergistic tumor therapy into a single‐component nanoplatform is much promising for high efficacy tumor treatment but still in a great challenge. Herein, a smart and versatile nanotheranostic platform based on hollow mesoporous Prussian blue nanoparticles (HMPBs) with perfluoropentane (PFP) and doxorubicin (DOX) inside, has been designed, for the first time, to achieve the distinct in vivo synergistic chemo‐thermal tumor therapy and synchronous diagnosis and monitoring by ultrasound (US)/photoacoustic (PA) dual mode imaging. The prepared HMPBs show excellent photothermal conversion properties with large molar extinction coefficient (≈1.2 × 10¹¹m ^?1 cm^?1) and extremely high photothermal conversion efficiency (41.4%). Such a novel theranostic nanoplatform is expected to overcome the inevitable tumor recurrence and metastasis resulting from the inhomogeneous ablation of single thermal therapy, which will find a promising prospect in the application of noninvasive cancer therapy.     

PEGylated Polypyrrole Nanoparticles Conjugating Gadolinium Chelates for Dual‐Modal MRI/Photoacoustic Imaging Guided Photothermal Therapy of Cancer

Polypyrrole nanoparticles conjugating gadolinium chelates were successfully fabricated for dual‐modal magnetic resonance imaging (MRI) and photoacoustic imaging guided photothermal therapy of cancer, from a mixture of pyrrole and pyrrole‐1‐propanoic acid through a facile one‐step aqueous dispersion polymerization, followed by covalent attachment of gadolinium chelate, using polyethylene glycol as a linker. The obtained PEGylated poly­pyrrole nanoparticles conjugating gadolinium chelates (Gd‐PEG‐PPy NPs), sized around around 70 nm, exhibited a high T₁ relaxivity coefficient of 10.61 L mm ^?1 s^?1, more than twice as high as that of the relating free Gd³⁺ complex (4.2 L mm ^–1 s^?1). After 24 h intravenous injection of Gd‐PEG‐PPy NPs, the tumor sites exhibited obvious enhancement in both T₁‐weighted MRI intensity and photoacoustic signal compared with that before injection, indicating the efficient accumulation of Gd‐PEG‐PPy NPs due to the introduction of the PEG layer onto the particle surface. In addition, tumor growth could be effectively inhibited after treatment with Gd‐PEG‐PPy NPs in combination with near‐infrared laser irradiation. The passive targeting and high MRI/photo­acoustic contrast capability of Gd‐PEG‐PPy NPs are quite favorable for precise cancer diagnosing and locating the tumor site to guide the external laser irradiation for photothermal ablation of tumors without damaging the surrounding healthy tissues. Therefore, Gd‐PEG‐PPy NPs may assist in better monitoring the therapeutic process, and contribute to developing more effective “personalized medicine,” showing great potential for cancer diagnosis and therapy.     

Semiconducting Nanocomposite with AIEgen‐Triggered Enhanced Photoluminescence and Photodegradation for Dual‐Modality Tumor Imaging and Therapy

Semiconducting polymer nanoparticles (SPNs) have potential in biological applications. While some SPNs have significant photothermal conversion efficiencies (PCEs) as photothermal and photoacoustic agents, other SPNs offer high fluorescence yields as photoluminescent agents. However, the energy balance distribution in SPNs inhibits their successful applications in photoluminescence/photoacoustic (PL/PA) dual‐modality imaging. Additionally, the ultrastability of SPNs in vivo may cause damage to organisms. This work reports nanocomposite semiconducting polymer and tetraphenylethene nanoparticles (STNPs) constructed by semiconducting polymers (SPs) and tetraphenylethene aggregation‐induced emission luminogens (TPE AIEgens). The SP SPC10 endows good photothermal conversion ability, and the AIEgen TPBM supports enhanced photoluminescence of the STNPs. The results show that the STNPs can act as PL/PA dual‐modality imaging agents. The signal‐to‐noise (S/N) ratio in the PL modality reaches 8.7, and the imaging depth in the PA modality is 5.8 mm. The SPC10 in the STNPs can be decomposed under 90 mW cm^?2 white light irradiation in 6 h without any other additional agents. Furthermore, the STNPs are sufficient for the treatment of xenograft 4T1 tumor‐bearing mice based on photothermal therapy. The nanocomposite STNPs achieve optimized dual‐modality PL/PA imaging and the AIEgen‐triggered in situ photodegradation of SPNs. These properties indicate the significant potential of STNPs in clinical diagnosis and noninvasive therapy.     

Photoacoustic Imaging of Embryonic Stem Cell‐Derived Cardiomyocytes in Living Hearts with Ultrasensitive Semiconducting Polymer Nanoparticles

Human embryonic stem cell‐derived cardiomyocytes (hESC‐CMs) have become promising tools to repair injured hearts. To achieve optimal outcomes, advanced molecular imaging methods are essential to accurately track these transplanted cells in the heart. In this study, it is demonstrated for the first time that a class of photoacoustic nanoparticles (PANPs) incorporating semiconducting polymers (SPs) as contrast agents can be used in the photoacoustic imaging (PAI) of transplanted hESC‐CMs in living mouse hearts. This is achieved by virtue of two benefits of PANPs. First, strong photoacoustic (PA) signals and specific spectral features of SPs allow PAI to sensitively detect and distinguish a small number of PANP‐labeled cells (2000) from background tissues. Second, the PANPs show a high efficiency for hESC‐CM labeling without adverse effects on cell structure, function, and gene expression. Assisted by ultrasound imaging, the delivery and engraftment of hESC‐CMs in living mouse hearts can be assessed by PANP‐based PAI with high spatial resolution (≈100 µm). In summary, this study explores and validates a novel application of SPs as a PA contrast agent to track labeled cells with high sensitivity and accuracy in vivo, highlighting the advantages of integrating PAI and PANPs to advance cardiac regenerative therapies.     

Selective Artificial Receptors Based on Micropatterned Surface‐Imprinted Polymers for Label‐Free Detection of Proteins by SPR Imaging

A novel concept to generate micropatterned surface‐imprinted polymers (SIPs) for protein recognition by using standard photolithographic technology is introduced. Avidin‐imprinted poly(3,4‐ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT/PSS) conducting polymer microbands are prepared directly on surface plasmon resonance (SPR) chips, which enable convenient label‐free monitoring of the binding events. The novel surface‐imprinted microstructures bind avidin, the template protein, with dissociation constants in the submicromolar range (125 nM ). The SIPs have an avidin binding capacity approximately one order of magnitude higher than the corresponding nonimprinted polymers and are able to discriminate among functional homologues of avidin, i.e., neutravidin, extravidin, and streptavidin.     

RGD‐Conjugated Nanoscale Coordination Polymers for Targeted T1‐ and T2‐weighted Magnetic Resonance Imaging of Tumors in Vivo

Development of multifunctional nanoscale coordination polymers (NCPs) allowing for T₁‐ and T₂‐weighted targeted magnetic resonance (MR) imaging of tumors could significantly improve the diagnosis accuracy. In this study, nanoscale coordination polymers (NCPs) with a diameter of ≈80 nm are obtained with 1,1′‐dicarboxyl ferrocene (Fc) as building blocks and magnetic gadolinium(III) ions as metallic nodes using a nanoprecipitation method, then further aminated through silanization. The amine‐functionalized Fc‐Gd@SiO₂ NCPs enable the covalent conjugation of a fluorescent rhodamine dye (RBITC) and an arginine‐glycine‐aspartic acid (RGD) peptide as a targeting ligand onto their surface. The formed water‐dispersible Fc‐Gd@SiO₂(RBITC)–RGD NCPs exhibit a low cytotoxicity, as confirmed by MTT assay. They have a longitudinal relaxivity (r₁) of 5.1 mM^?1 s^?1 and transversal relaxivity (r₂) of 21.7 mM^?1 s^?1, suggesting their possible use as both T₁‐positive and T₂‐negative contrast agents. In vivo MR imaging experiments show that the signal of tumor over‐expressing high affinity α_vβ₃ integrin from T₁‐weighted MR imaging is positively enhanced 47±5%, and negatively decreased 33±5% from T₂‐weighted MR imaging after intravenous injection of Fc‐Gd@SiO₂(RBITC)–RGD NCPs.     

All‐in‐One Phototheranostics: Single Laser Triggers NIR‐II Fluorescence/Photoacoustic Imaging Guided Photothermal/Photodynamic/Chemo Combination Therapy

Development of single near‐infrared (NIR) laser triggered phototheranostics for multimodal imaging guided combination therapy is highly desirable but is still a big challenge. Herein, a novel small‐molecule dye DPP‐BT is designed and synthesized, which shows strong absorption in the first NIR window (NIR‐I) and fluorescence emission in the second NIR region (NIR‐II). Such a dye not only acts as a dual‐modal contrast agent for NIR‐II fluorescence and photoacoustic (PA) imaging, but also serves as a combined therapeutic agent for photothermal therapy (PTT) and photodynamic therapy (PDT). The single NIR laser triggered all‐in‐one phototheranostic nanoparticles are constructed by encapsulating the dye DPP‐BT, chemotherapy drug DOX, and natural phase‐change materials with a folic acid functionalized amphiphile. Notably, under NIR laser irradiation, DOX can effectively release from such nanoparticles via NIR‐induced hyperthermia of DPP‐BT. By intravenous injection of such nanoparticles into Hela tumor‐bearing mice, the tumor size and location can be accurately observed via NIR‐II fluorescence/PA dual‐modal imaging. From in vitro and in vivo therapy results, such nanoparticles simultaneously present remarkable antitumor efficacy by PTT/PDT/chemo combination therapy, which is triggered by a single NIR laser. Overall, this work provides an innovative strategy to design and construct all‐in‐one nanoplatforms for clinical phototheranostics.     

An Integrated Multifunctional Nanoplatform for Deep‐Tissue Dual‐Mode Imaging

The combination of biocompatible superparamagnetic and photoluminescent nanoparticles (NPs) is intensively studied as highly promising multifunctional (magnetic confinement and targeting, imaging, etc.) tools in biomedical applications. However, most of these hybrid NPs exhibit low signal contrast and shallow tissue penetration for optical imaging due to tissue‐induced optical extinction and autofluorescence, since in many cases, their photoluminescent components emit in the visible spectral range. Yet, the search for multifunctional NPs suitable for high photoluminescence signal‐to‐noise ratio, deep‐tissue imaging is still ongoing. Herein, a biocompatible core/shell/shell sandwich structured Fe₃O₄@SiO₂@NaYF₄:Nd³⁺ nanoplatform possessing excellent superparamagnetic and near‐infrared (excitation) to near‐infrared (emission), i.e., NIR‐to‐NIR photoluminescence properties is developed. They can be rapidly magnetically confined, allowing the NIR photoluminescence signal to be detected through a tissue as thick as 13 mm, accompanied by high T₂ relaxivity in magnetic resonance imaging. The fact that both the excitation and emission wavelengths of these NPs are in the optically transparent biological windows, along with excellent photostability, fast magnetic response, significant T₂‐contrast enhancement, and negligible cytotoxicity, makes them extremely promising for use in high‐resolution, deep‐tissue dual‐mode (optical and magnetic resonance) in vivo imaging and magnetic‐driven applications.     

Thermoresponsive Semiconducting Polymer Nanoparticles for Contrast‐Enhanced Photoacoustic Imaging

Photoacoustic (PA) agents with biomarker‐activated signals are developed to enhance the signal‐to‐background ratios (SBRs) for in vivo imaging; however, their SBRs still heavily rely on the concentration difference of biomarkers between diseased and normal tissues. By contrast, external stimuli can provide a remote way to noninvasively control the signal generation from the PA agents and in turn enhance SBR, which are less exploited. This study reports the development of thermoresponsive semiconducting polymer brush with poly(N,N‐dimethylacrylamide)‐r‐(hydroxypropyl acrylate) (PDMA‐r‐HPA) grafts for contrast‐enhanced in vivo imaging. Such a polymer is amphiphilic and can self‐assemble into the nanoparticle (termed as SPNph1) in an aqueous medium, and has lower critical solution temperatures (LCSTs) at 48 °C. Thus, SPNph1 not only has higher photothermal conversion efficiency than the control polymer without PDMA‐r‐HPA grafts, but also can undergo phase separation to form large nanoparticles, leading to enhanced PA signals above LCST. The thermoresponsive PA property of SPNph1 enables in situ remote manipulation of PA signals by photoirradiation to further enhance the tumor SBR. Thus, this study introduces a new generation of organic PA agents with thermoresponsive signal for high‐contrast in vivo imaging.     

Nanostructural Control Enables Optimized Photoacoustic–Fluorescence–Magnetic Resonance Multimodal Imaging and Photothermal Therapy of Brain Tumor

The performance of current multimodal imaging contrast agents is often constrained by the tunability of nanomaterial structural design. Herein, the influence of nanostructure on the overall imaging performance of a composite nanomaterial for multimodal imaging of brain tumors is studied. Newly designed near‐infrared molecules (TC1) are encapsulated into nanocomposites with ultrasmall iron oxide nanoparticles (UIONPs), forming stable nanoagents for multimodal imaging and photothermal therapy (PTT). Through a modified nanoprecipitation method, the synthesis of nanocomposites denoted as HALF is realized, in which UIONPs are restricted to half of the nanosphere. Such a unique nanostructure that physically separates TC1 and UIONPs is found with capabilities of mitigating fluorescence quenching, preserving the good performance of photoacoustic imaging, and enhancing the magnetic resonance imaging signals. Decorated with a peptide ligand cRGD for better brain tumor targeting, HALF‐cRGD is evaluated both in vitro and in vivo as imaging contrast agents and photothermal therapeutic agents. The good imaging performance and PTT effect of HALF‐cRGD in mice models indicate that the rational design and control of nanostructures could optimize multimodal imaging performance using the same components.     

Ultrasmall Semiconducting Polymer Dots with Rapid Clearance for Second Near‐Infrared Photoacoustic Imaging and Photothermal Cancer Therapy

Phototheranostic agents in the second near‐infrared (NIR‐II) window (1000–1700 nm) are emerging as a promising theranostic platform for precision medicine due to enhanced penetration depth and minimized tissue exposure. The development of metabolizable NIR‐II nanoagents for imaging‐guided therapy are essential for noninvasive disease diagnosis and precise ablation of tumors. Herein, metabolizable highly absorbing NIR‐II conjugated polymer dots (Pdots) are reported for the first time for photoacoustic imaging guided photothermal therapy (PTT). The unique design of low‐bandgap D‐A π‐conjugated polymer (DPP‐BTzTD) together with modified nanoreprecipitation conditions allows to fabricate NIR‐II absorbing Pdots with ultrasmall (4 nm) particle size. Extensive experimental tests demonstrate that the constructed Pdots exhibit good biocompatibility, excellent photostability, bright photoacoustic signals, and high photothermal conversion efficiency (53%). In addition, upon tail‐vein intravenous injection of tumor‐bearing mice, Pdots also show high‐efficient tumor ablation capability with rapid excretion from the body. In particular, both in vitro and in vivo assays indicate that the Pdots possess remarkable PTT performance under irradiation with a 1064 nm laser with 0.5 W cm^?2, which is much lower than its maximum permissible exposure limit of 1 W cm^?2. This pilot study thus paves a novel avenue for the development of organic semiconducting nanoagents for future clinical translation.     

Paper‐Based Electrochromic Devices Enabled by Nanocellulose‐Coated Substrates

As environmental considerations for both the processing and disposal of electronic devices become increasingly important, the ability to replace plastic and glass substrates with bioderived and biodegradable materials remains a major technological goal. Here, the use of cellulose nanofiber‐coated paper is explored as an environmentally benign substrate for preparing low‐resistance (460 Ω sq^?1), colorless (a* = ?2.3, b* = ?2.7) printed poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) electrodes. The PEDOT:PSS/paper electrodes support the reversible oxidation of three electrochromic polymers (ECPs) (cyan, magenta, and yellow), affording the possibility for fully printed, color displays on paper. Lateral electrochromic devices (ECDs) incorporating an ion gel electrolyte are demonstrated where a magenta‐to‐colorless device achieves a color contrast (ΔE*) of 56 owing to a highly color‐neutral bleached state of the ECP (a* = ?0.5, b* = 2.9). Black‐to‐colorless devices achieve ΔE* = 29 and are able to retain 86% of their color contrast after 9000 switches. The switching times of these lateral devices are quantified through colorimetric image analysis which shows comparable performance for devices constructed on paper as devices using ITO/glass electrodes (10 Ω sq^?1). The paper ECDs are then combusted in air leaving 3% of the initial mass at 600 °C, highlighting this approach as a promising route toward disposable displays.     

Self‐Assembly of Semiconducting Polymer Amphiphiles for In Vivo Photoacoustic Imaging

Despite the advantages of semiconducting polymer nanoparticles (SPNs) over other inorganic nanoparticles for photoacoustic (PA) imaging, their synthetic method is generally limited to nanoprecipitation, which is likely to cause the issue of nanoparticle dissociation. The synthesis of near‐infrared (NIR) absorbing semiconducting polymer amphiphiles (SPAs) that can spontaneously self‐assemble into homogeneous nanoparticles for in vivo PA imaging is reported. As compared with their counterpart nanoparticles (SPN1) prepared through nanoprecipitation, SPAs generally have higher fluorescence quantum yields but similar size and PA brightness, making them superior over SPN1. Optical and simulation studies reveal that the poly(ethylene glycol) (PEG) grafting density plays a critical role in determining the packing of SP segments inside the core of nanoparticles, consequently affecting the optical properties. The small size and structurally stable nanostructure, in conjunction with a dense PEG shell, allow SPAs to passively target tumors of living mice after systemic administration, permitting both PA and fluorescence imaging of the tumors at signals that are ≈1.5‐fold higher than that of liver. This study thus not only provides the first generation of amphiphilic optically active polymers for PA imaging, but also highlights the molecular guidelines for the development of organic NIR imaging nanomaterials.