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X-ray computed tomography (CT) has an important role in precision medicine. However, CT contrast agents with high efficiency and the ability to translate diagnostic accuracy into therapeutic intervention are scarce. Here, poly(diiododiacetylene) (PIDA), a conjugated polymer composed of only carbon and iodine atoms, is reported as an efficient CT contrast agent to bridge CT diagnostic imaging with therapeutic intervention. PIDA has a high iodine payload (>84 wt%), and the aggregation of nanofibrous PIDA can further amplify CT intensity and has improved geometrical and positional stability in vivo. Moreover, with a conjugated backbone, PIDA is in deep blue color, making it dually visible by both CT imaging and the naked eyes. The performance of PIDA in CT-guided preoperative planning and visualization-guided surgery is validated using orthotopic xenograft rat models. In addition, PIDA excels clinical fiducial markers of imaging-guided radiotherapy in efficiency and biocompatibility, and exhibits successful guidance of robotic radiotherapy on Beagles, demonstrating clinical potential to translate CT diagnosis accuracy into therapeutic intervention for precision medicine. Poly(diiododiacetylene)—PIDA—contains iodine atoms, which are commonly found in computed tomography contrast agents. Here, the authors find that PIDA can function as a contrast agent and can also be used as a visual marker to delineate tumour margins.

Glioblastoma multiforme (GBM) is one of the most fatal malignancies due to the existence of blood-brain barrier (BBB) and the difficulty to maintain an effective drug accumulation in deep GBM lesions. Here we present a biomimetic nanogel system that can be precisely activated by near infrared (NIR) irradiation to achieve BBB crossing and deep tumor penetration of drugs. Synthesized by crosslinking pullulan and poly(deca-4,6-diynedioic acid) (PDDA) and loaded with temozolomide and indocyanine green (ICG), the nanogels are inert to endogenous oxidative conditions but can be selectively disintegrated by ICG-generated reactive oxygen species upon NIR irradiation. Camouflaging the nanogels with apolipoprotein E peptide-decorated erythrocyte membrane further allows prolonged blood circulation and active tumor targeting. The precisely controlled NIR irradiation on tumor lesions excites ICG and deforms the cumulated nanogels to trigger burst drug release for facilitated BBB permeation and infiltration into distal tumor cells. These NIR-activatable biomimetic nanogels suppress the tumor growth in orthotopic GBM and GBM stem cells-bearing mouse models with significantly extended survival. Effective drug accumulation in deep glioblastoma multiforme (GBM) lesions remains challenging due to the blood brain barrier. Here, the authors develop a biomimetic nanogel system activated by near infrared irradiation and show high efficacy in orthotopic GBM and GBM stem cells-bearing mouse models.

Combining immune checkpoint blockade (ICB) therapy with photodynamic therapy (PDT) holds great potential in treating immunologically “cold” tumors, but photo-generated reactive oxygen species (ROS) can inevitably damage co-administered ICB antibodies, hence hampering the therapeutic outcome. Here we create a ROS-responsive hydrogel to realize the sustained co-delivery of photosensitizers and ICB antibodies. During PDT, the hydrogel skeleton poly(deca-4,6-diynedioic acid) (PDDA) protects ICB antibodies by scavenging the harmful ROS, and at the same time, triggers the gradual degradation of the hydrogel to release the drugs in a controlled manner. More interestingly, we can visualize the ROS-responsive hydrogel degradation by Raman imaging, given the ultrastrong and degradation-correlative Raman signal of PDDA in the cellular silent window. A single administration of the hydrogel not only completely inhibits the long-term postoperative recurrence and metastasis of 4T1-tumor-bearing mice, but also effectively restrains the growth of re-challenged tumors. The PDDA-based ROS-responsive hydrogel herein paves a promising way for the durable synergy of PDT and ICB therapy. Combined immune checkpoint blockade (ICB) and photodynamic therapies have huge potential but suffer from possible damage of the antibodies. Here, the authors create a ROS-responsive hydrogel that protects the ICB antibodies and allows for sustained co-delivery and demonstrate restrained regrowth of tumours in vivo.

Diabetic wounds are usually entangled in a disorganized and self-perpetuating microenvironment and accompanied by a prolonged delay in tissue repair. Sustained and coordinated microenvironment regulation and tissue regeneration are key to the healing process of diabetic wounds, yet they continue to pose a formidable challenge. Here we report a rational double-layered dressing design based on chitosan and a degradable conjugated polymer polydiacetylene, poly(deca-4,6-diynedioic acid) (PDDA), that can meet this intricate requirement. With an alternating ene-yne backbone, PDDA degrades when reacting with various types of reactive oxygen species (ROS), and more importantly, generates proliferative succinic acid as a major degradant. Inheriting from PDDA, the developed PDDA-chitosan double layer dressing (PCD) can eliminate ROS in the microenvironment of diabetic wounds, alleviate inflammation, and downregulate gene expression of innate immune receptors. PCD degradation also triggers simultaneous release of succinic acid in a sustainable manner, enabling long-term promotion on tissue regeneration. We have validated the biocompatibility and excellent performance of PCD in expediting the wound healing on both diabetic mouse and porcine models, which underscores the significant translational potential of this microenvironment-modulating, growth-promoting wound dressing in diabetic wounds care. Sustained and coordinated microenvironment regulation and tissue regeneration are vital for the healing process of diabetic wounds but elusive. Here, the authors report a double-layered, microenvironment-modulating dressing able to eliminate reactive oxygen species and generate proliferative degradants that promote angiogenesis and tissue regeneration in diabetic wounds.

Live-cell Raman imaging based on bioorthogonal Raman probes with distinct signals in the cellular Raman-silent region (1800–2800 cm −1 ) has attracted great interest in recent years. We report here a class of water-soluble and biocompatible polydiacetylenes with intrinsic ultrastrong alkyne Raman signals that locate in this region for organelle-targeting live-cell Raman imaging. Using a host-guest topochemical polymerization strategy, we have synthesized a water-soluble and functionalizable master polydiacetylene, namely poly(deca-4,6-diynedioic acid) (PDDA), which possesses significantly enhanced (up to ~10 4 fold) alkyne vibration compared to conventional alkyne Raman probes. In addition, PDDA can be used as a general platform for multi-functional ultrastrong Raman probes. We achieve high quality live-cell stimulated Raman scattering imaging on the basis of modified PDDA. The polydiacetylene-based Raman probes represent ultrastrong intrinsic Raman imaging agents in the Raman-silent region (without any Raman enhancer), and the flexible functionalization of this material holds great promise for its potential diverse applications. Raman probes which operate in the cellular silent region are of interest for live cell imaging. Here, the authors report on the development of a water soluble polydiacetylene Raman probe with enhanced Raman signal in the silent region which can be functionalised for organelle targeting and demonstrate application.

Raman spectroscopy offers unique molecular fingerprinting capability for cancer diagnosis and monitoring, yet its biomedical application is fundamentally limited by weak intrinsic signals and complex biological backgrounds. Composite Raman probes, particularly surface-enhanced Raman scattering (SERS)—based systems, overcome these limitations through synergistic electromagnetic and chemical enhancement combined with functional integration. By engineering plasmonic nanostructures, interfacial electronic states, and molecular architectures, composite Raman probes achieve synergistic electromagnetic and chemical enhancement while incorporating biorecognition units, reporter molecules, and protective coatings to improve stability, specificity, and biocompatibility. In recent years, these probes have evolved from simple signal tags into multifunctional platforms capable of ultrasensitive tumor biomarker detection, high-contrast imaging, surgical guidance, therapy monitoring, and dynamic analysis of the tumor microenvironment (TME). This review systematically summarizes recent advances in composite Raman probes for oncological applications, with an emphasis on material design strategies, enhancement mechanisms, and stimulus-responsive regulation. Representative applications at both molecular and tissue levels are highlighted, including nucleic acid, protein, and exosome detection, as well as in vivo imaging and microenvironmental sensing. Finally, current challenges and future perspectives toward clinical translation are discussed, aiming to provide guidance for the rational design of next-generation Raman probes for precision oncology.

In recent years, yeast glucan particles (YGPs) have garnered significant attention as novel oral drug delivery carriers, owing to their superior biocompatibility, specific targeting capabilities, and intrinsic immunomodulatory properties. The yeast cell wall is primarily composed of β-glucan and mannan, with minor amounts of proteins and lipids. Among these, β-1,3-glucan serves as the pivotal functional component. It not only provides a physical barrier protecting payloads from gastric acidity and enzymatic degradation but also functions as a targeting ligand. By specifically binding to M cells in Peyer’s patches and Dectin-1 receptors on macrophages and dendritic cells, β-1,3-glucan facilitates precise drug delivery to gut-associated lymphoid tissue (GALT) or macrophage-rich inflammatory sites. Consequently, β-1,3-glucan-based YGPs demonstrate immense potential in oral targeted delivery systems for macrophage-associated pathologies. However, native YGPs, constrained by their inherent porous architecture and relatively simple physicochemical properties, often fall short of meeting the complex requirements for precise encapsulation, controlled release, and multifunctionality. To address these limitations, current research is actively exploring the functionalization of YGPs with various composite materials to engineer advanced delivery platforms. This review introduces the composition, structural characteristics, and fabrication methodologies of YGPs, alongside their specific merits and limitations in oral drug delivery. Furthermore, it critically analyzes strategies for modifying YGPs with composite materials to overcome delivery barriers. Finally, the review discusses their therapeutic applications across various diseases and outlines future developmental trends.

The gut microbiota is closely associated with human health, and alterations in gut microbiota can influence various physiological and pathological activities in the human body. Therefore, microbiota regulation has become an important strategy in current disease treatment, albeit facing numerous challenges. Nanomaterials, owing to their excellent protective properties, drug release capabilities, targeting abilities, and good biocompatibility, have been widely developed and utilized in pharmaceuticals and dietary fields. In recent years, significant progress has been made in research on utilizing nanomaterials to assist in regulating gut microbiota for disease intervention. This review explores the latest advancements in the application of nanomaterials for microbiota regulation and offers insights into the future development of nanomaterials in modulating gut microbiota.

The energy dissipation pathways of a photosensitizer for phototherapies, including photodynamic therapy (PDT) and photothermal therapy (PTT), compete directly with that of its fluorescence (FL) emission. Enriching heavy atoms on the π‐conjugated systems and aggregation‐caused quenching are two effective methods to turn off the FL emission of photosensitizers, which is expected to boost the intersystem crossing (for PDT) and nonradiative transition (for PTT) of photosensitizers for maximized phototherapeutic efficacy. Following this approach, an all‐iodine‐substituted polydiacetylene aggregate poly(diiododiacetylene) (PIDA) has been developed, which shows a superior near infrared absorption (ε808nm = 26.1 g−1 cm−1 L) with completely blocked FL, as well as high efficiency of reactive oxygen species generation (nearly 45 folds of indocyanine green) and photothermal conversion (33.4%). To make the insoluble fibrillar PIDA aggregates favorable for systemic administration, they are converted into nanospheres through a pre‐polymerization morphology transformation strategy. The in vivo study on a 4T1 tumor‐bearing mouse model demonstrates that PIDA nanospheres can almost eliminate the tumor entirely in 16 days and prolong the survival time of mice to over 60 days, validating their effective phototherapeutic response through the strategy of inhibiting FL for boosted intersystem crossing and nonradiative transition. An atomic‐iodine‐substituted polydiacetylene aggregate poly(diiododiacetylene) (PIDA) was developed to completely block fluorescence emission via heavy atom effects as well as indefinitely extended π‐conjugation. The special structure gives it ultraeffective phototherapy effects under NIR light irradiation. By a newly preparation method, the morphology of PIDA dispersion transformed from fibers to nanospheres, which was suitable for i.v. systematically treatment.

Numerous mechanisms have been proposed for polymerization to provide qualitative and quantitative prediction of how monomers spatially and temporally arrange into the polymeric chains. However, less is known about this process at the molecular level because the ultrafast chemical reaction is inaccessible for any form of microscope so far. Here, to address this unmet challenge, a stimulated Raman scattering microscope based on collinear multiple beams (COMB‐SRS) is demonstrated, which allows label‐free molecular imaging of polymer synthesis in action at speed of 2000 frames per second. The field of view of the developed 2 kHz SRS microscope is 30 × 28 µm2 with 50 × 46 pixels and 7 µs dwell time. By catching up the speed of chemical reaction, COMB‐SRS is able to quantitatively visualize the ultrafast dynamics of molecular vibrations with submicron spatial resolution and sub‐millisecond temporal resolution. The propagating polymer waves driven by reaction rate and persistent UV initiation are observed in situ. This methodology is expected to permit the development of novel functional polymers, controllable photoresists, 3D printing, and other new polymerization technologies. An ultrafast collinear multiple beam‐based stimulated Raman scattering microscope is developed to achieve direct imaging and quantification of polymerization kinetics in situ. By label‐free and molecular imaging of the polymerization process in action at a frame rate of 2 kHz, the polymer wave is observed, which is actually driven by radicals persistently generated in the UV initiation center.