Bioinspired cytomembrane coating besieges tumor for blocking metabolite transportation.

The metabolite transport inhibition of tumor cells holds promise to achieve anti-tumor efficacy. Herein, we presented an innovative strategy to hinder the delivery of metabolites through the in-situ besieging tumor cells with polyphenolic polymers that strongly adhere to the cytomembrane of tumor cells. Simultaneously, these polymers underwent self-crosslinking under the induction of tumor oxidative stress microenvironment to form an adhesive coating on the surface of the tumor cells. This polyphenol coating effectively obstructed glucose uptake, reducing metabolic products such as lactic acid, glutathione, and adenosine triphosphate, while also causing reactive oxygen species to accumulate in the tumor cells. The investigation of various tumor models, including 2D cells, 3D multicellular tumor spheroids, and xenograft tumors, demonstrated that the polyphenolic polymers effectively inhibited the growth of tumor cells by blocking key metabolite transport processes. Moreover, this highly adhesive coating could bind tumor cells to suppress their metastasis and invasion. This work identified polyphenolic polymers as a promising anticancer candidate with a mechanism by impeding the mass transport of tumor cells.

Copper-Bacteriochlorin Nanosheet as a Specific Pyroptosis Inducer for Robust Tumor Immunotherapy.

Pyroptosis is increasingly considered a new weathervane in cancer immune therapy. However, triggering specific pyroptotic tumor cell death while preserving normal cells still remains a major challenge. Herein, a brand-new pyroptosis inducer, copper-bacteriochlorin nanosheet (Cu-TBB), is designed. The synthesized Cu-TBB can be activated to an "on" state in the tumor microenvironment with glutathione (GSH) overexpression, leading to the release of Cu+ and TBB, respectively. Intriguingly, the released Cu+ can drive cascade reactions to produce O2 -• and highly toxic ·OH in cells. Additionally, the released TBB can also generate O2 -• and 1 O2 upon 750 nm laser irradiation. Encouragingly, both Cu+ -driven cascade reactions and photodynamic therapy pathways result in potent pyroptosis along with dendritic cell maturation and T cell priming, thus simultaneously eliminating the primary tumors and inhibiting the distant tumor growth and metastases. Conclusively, the well-designed Cu-TBB nanosheet is shown to trigger specific pyroptosis in vitro and in vivo, leading to enhanced tumor immunogenicity and antitumor efficacy while minimizing systemic side effects.

Nonreleasing AgNP Colloids Composite Hydrogel with Potent Hemostatic, Photodynamic Bactericidal and Wound Healing-Promoting Properties.

Reactive oxygen species (ROS) produced by noble metallic nanoparticles under visible light is an effective way to combat drug-resistant bacteria colonized on the wound. However, the photocatalytic efficiency of noble metallic nanoparticles is limited by its self-aggregation in water media. Moreover, the fast release of noble metallic ions from nanoparticles might engender cellular toxicity and hazardous environmental issues. Herein, we chose AgNPs, the most common plasmonic noble metallic nanoparticles, as an example, modifying the surface of AgNPs with oleic acid and n-butylamine and imbedded them into calcium alginate (CA) hydrogel that holds tissue adhesion, rapid hemostatic, sunlight-sensitive antibacterial and anti-inflammatory abilities, and thus effectively promotes the healing of wounds. Unlike conventional AgNP-based materials, the constrain of colloids and hydrogel networks hinders the leach of Ag+. Nonetheless, the CA/Ag hydrogels exhibit on-demand photodynamic antibacterial efficacy due to the generation of ROS under visible light. In addition, the CA/Ag hydrogel can effectively stop the hemorrhage in a mouse liver bleeding model due to their skin-adaptive flexibility and tissue adhesiveness. The potent sunlight-responsive antibacterial activity of the CA/Ag hydrogel can effectively kill multidrug-resistant bacteria both in vitro (>99.999%) and in vivo (>99.9%), while the diminished Ag+ release guarantees its biocompatibility. The CA/Ag hydrogel significantly promotes the wound healing process by the downregulation of proinflammatory cytokines (TNF-α and IL-6) in a rodent full-thickness cutaneous wound model. Overall, the proposed multifunctional CA/Ag nanocomposite hydrogel has excellent prospects as an advanced wound dressing.

Metal-Phenolic Networks Assembled on TiO2 Nanospikes for Antimicrobial Peptide Deposition and Osteoconductivity Enhancement in Orthopedic Applications.

The lack of antimicrobial and osteoconductive activities of titanium (Ti) for orthopedic implants has led to problems such as infection and structural looseness, which bring physical and psychological sufferings to patients as well as economic burden on the healthcare system. To endow Ti implants with anti-infective function and bioactivity, in this study, we successfully constructed TiO2 nanospike (TNS) structure on the surface of Ti followed by assembling metal-polyphenol networks (MPNs) and depositing antimicrobial peptides (AMPs). The TNSs' structure can disrupt the bacteria by physical puncture, and it was also proved to have excellent photothermal conversion performance upon near-infrared light irradiation. Furthermore, with the assistance of contact-active chemo bactericidal efficacy of AMPs, TNS-MPN-AMP nanocoating achieved physical/photothermal/chemo triple-synergistic therapy against pathogenic bacteria. The anti-infective efficiency of this multimodal treatment was obviously improved, with an antibacterial ratio of >99.99% in vitro and 95.03% in vivo. Moreover, the spike-like nanostructure of TNSs and the bioactive groups from MPNs and AMPs not only demonstrated desirable biocompatibility but also promoted the surface hydroxyapatite formation in simulated body fluid for further osseointegration enhancement. Altogether, this multifaceted TNS-MPN-AMP nanocoating endowed Ti implants with enhanced antibacterial activity, excellent cytocompatibility, and desirable osteoconductive ability.

Carbon dots nanophotosensitizers with tunable reactive oxygen species generation for mitochondrion-targeted type I/II photodynamic therapy.

Carbon dots (CDs) have emerged as promising nanomaterials for bioimaging-guided photodynamic therapy (PDT). However, designing red-emissive CDs (RCDs) with tunable type I and type II reactive oxygen species (ROS) generation to simultaneously meet PDT applications in aerobic and hypoxic scenarios still remain major challenges. Herein, three types of RCDs with maximum emission at approximately 680 nm are successfully prepared. It is noteworthy that they exhibit the adjustable ROS production with equal superoxide anion (via type I PDT) and incremental singlet oxygen (via type II PDT). Detailed structural and optical characterizations along with theoretical calculation reveal that the unique type I/II ROS formation mainly depends on the core sizes and surface states of RCDs, which determine their identical redox potentials and tapering energy gaps between singlet- and triplet states, respectively. Additionally, due to the inherent mitochondria targeting capability, RCDs enable themselves to induce cell programmed death via activating mitochondrion-mediated apoptotic pathways. This work exploits the unprecedented RCDs with tunable type I and type II ROS generation that could ensure highly efficient tumor eradication both in vitro and in vivo, even under the harsh tumor microenvironment, providing a new prospect for CDs as nanophotosensitizers to conquer the limitations of single type PDT.

Iron phthalocyanine-derived nanozyme as dual reactive oxygen species generation accelerator for photothermally enhanced tumor catalytic therapy.

Nanozymes are artificial enzymes that mimic natural enzyme-like activities and show great promise for tumor catalytic therapy. However, new nanozymes with multiple catalytic activities for multifunctional nanotheranostic use remain challenging to design. Herein, for the first time, iron phthalocyanine (Fe(II)Pc) was assembled with poly(l-lactide-co-glycolide)-block-poly(ethylene glycol) to prepare an Fe(II)Pc assembly (denoted as Fe(II)Pc-A). The obtained Fe(II)Pc-A could be applied as a smart near-infrared (NIR) light-responsive nanotheranostic for simultaneous photoacoustic imaging-guided photothermal therapy. Notably, Fe(II)Pc-A possessed peroxidase, catalase, and oxidase mimicking activities, which could not only catalyze the conversion of intratumoral H2O2 to •OH, but also degrade H2O2 to generate O2 and continuously catalyze the conversion of O2 to cytotoxic O2•-. Impressively, the dual reactive oxygen species (ROS) generation of Fe(II)Pc-A was further remarkably enhanced by the endogenous acidity of the tumor microenvironment and the exogenous NIR light-responsive photothermal effect. Moreover, the O2 self-supplying ability of Fe(II)Pc-A led to increased generation of O2•- for enhancing catalytic therapy in hypoxic tumor. These collective properties of Fe(II)Pc-A nanozyme enabled it to be a dual ROS generation accelerator for photothermally enhanced tumor catalytic therapy. Thus, a new type of high-performance nanozyme for multifunctional nanotheranostic use toward cancer was presented.

An Electroluminodynamic Flexible Device for Highly Efficient Eradication of Drug-Resistant Bacteria.

Photodynamic therapy (PDT) has attracted wide attention in antibacterial applications due to its advantages of spatial-temporal selectivity, noninvasiveness, and low incidence to develop drug resistance. To make it more convenient, universal, and manipulatable for clinical application, a conceptually antibacterial strategy, namely "electroluminodynamic therapy" (ELDT), is presented by nanoassembly of an electroluminescent (EL) material and a photosensitizer, which is capable of generating reactive oxygen species (ROS) in situ under an electric field, i.e., the fluorescence emitted by the EL molecules excites the photosensitizer to generate singlet oxygen (1 O2 ), for the oxidative damage of pathogens. Based on the scheme of ELDT, a flexible therapeutic device is fabricated through a hydrogel loading with ELDT nanoagents, followed by integration with a flexible battery, satisfying the requirements of being light and wearable for wound dressings. The ELDT-based flexible device presents potent ROS-induced killing efficacies against drug-resistant bacteria (>99.9%), so as to effectively inhibit the superficial infection and promote the wound healing. This research reveals a proof-of-concept ELDT strategy as a prospective alternative to PDT, which avoids the utilization of a physical light source, and achieves convenient and effective killing of drug-resistant bacteria through a hydrogel-based flexible therapeutic device.

Antimicrobial Peptides and Macromolecules for Combating Microbial Infections: From Agents to Interfaces.

Bacterial resistance caused by the overuse of antibiotics and the shelter of biofilms has evolved into a global health crisis, which drives researchers to continuously explore antimicrobial molecules and strategies to fight against drug-resistant bacteria and biofilm-associated infections. Cationic antimicrobial peptides (AMPs) are considered to be a category of potential alternative for antibiotics owing to their excellent bactericidal potency and lesser likelihood of inducing drug resistance through their distinctive antimicrobial mechanisms. In this review, the hitherto reported plentiful action modes of AMPs are systematically classified into 15 types and three categories (membrane destructive, nondestructive membrane disturbance, and intracellular targeting mechanisms). Besides natural AMPs, cationic polypeptides, synthetic polymers, and biopolymers enable to achieve tunable antimicrobial properties by optimizing their structures. Subsequently, the applications of these cationic antimicrobial agents at the biointerface as contact-active surface coatings and multifunctional wound dressings are also emphasized here. At last, we provide our perspectives on the development of clinically significant cationic antimicrobials and related challenges in the translation of these materials.

Ultra-Sensitive, Deformable, and Transparent Triboelectric Tactile Sensor Based on Micro-Pyramid Patterned Ionic Hydrogel for Interactive Human-Machine Interfaces.

Rapid advances in wearable electronics and mechno-sensational human-machine interfaces impose great challenges in developing flexible and deformable tactile sensors with high efficiency, ultra-sensitivity, environment-tolerance, and self-sustainability. Herein, a tactile hydrogel sensor (THS) based on micro-pyramid-patterned double-network (DN) ionic organohydrogels to detect subtle pressure changes by measuring the variations of triboelectric output signal without an external power supply is reported. By the first time of pyramidal-patterned hydrogel fabrication method and laminated polydimethylsiloxane (PDMS) encapsulation process, the self-powered THS shows the advantages of remarkable flexibility, good transparency (≈85%), and excellent sensing performance, including extraordinary sensitivity (45.97 mV Pa-1 ), fast response (≈20 ms), very low limit of detection (50 Pa) as well as good stability (36 000 cycles). Moreover, with the LiBr immersion treatment method, the THS possesses excellent long-term hyper anti-freezing and anti-dehydrating properties, broad environmental tolerance (-20 to 60 °C), and instantaneous peak power density of 20 µW cm-2 , providing reliable contact outputs with different materials and detecting very slight human motions. By integrating the signal acquisition/process circuit, the THS with excellent self-power sensing ability is utilized as a switching button to control electric appliances and robotic hands by simulating human finger gestures, offering its great potentials for wearable and multi-functional electronic applications.

An Ultrastable Virus-Like Particle with a Carbon Dot Core and Expanded Sequence Plasticity.

Ordered bio-inorganic hybridization has evolved for the generation of high-performance materials in living organisms and inspires novel strategies to design artificial hybrid materials. Virus-like particles (VLPs) are attracting extensive interest as self-assembling systems and platforms in the fields of biotechnology and nanotechnology. However, as soft nanomaterials, their structural stability remains a general and fundamental problem in various applications. Here, an ultrastable VLP assembled from the major capsid protein (VP1) of simian virus 40 is reported, which contains a carbon dot (C-dot) core. Co-assembly of VP1 with C-dots led to homogeneous T = 1 VLPs with a fourfold increase in VLP yields. The resultant hybrid VLPs showed markedly enhanced structural stability and sequence plasticity. C-dots and a polyhistidine tag fused to the inner-protruding N-terminus of VP1 contributed synergistically to these enhancements, where extensive and strong noncovalent interactions on the C-dot/VP1 interfaces are responsible according to cryo-EM 3D reconstruction, molecular simulation, and affinity measurements. C-dot-enhanced ultrastable VLPs can serve as a new platform, enabling the fabrication of new architectures for bioimaging, theranostics, nanovaccines, etc. The hybridization strategy is simple and can easily be extended to other VLPs and protein nanoparticle systems.

Emerging photothermal-derived multimodal synergistic therapy in combating bacterial infections.

Due to the emerging bacterial resistance and the protection of tenacious biofilms, it is hard for the single antibacterial modality to achieve satisfactory therapeutic effects nowadays. In recent years, photothermal therapy (PTT)-derived multimodal synergistic treatments have received wide attention and exhibited cooperatively enhanced bactericidal activity. PTT features spatiotemporally controllable generation of hyperthermia that could eradicate bacteria without inducing resistance. The synergy of it with other treatments, such as chemotherapy, photo-dynamic/catalytic therapy (PDT/PCT), immunotherapy, and sonodynamic therapy (SDT), could lower the introduced laser density in PTT and avoid undesired overheating injury of normal tissues. Simultaneously, by heat-induced improvement of the bacterial membrane permeability, PTT is conducive for accelerated intracellular permeation of chemotherapeutic drugs as well as reactive oxygen species (ROS) generated by photosensitizers/sonosensitizers, and could promote infiltration of immune cells. Thereby, it could solve the currently existing sterilization deficiencies of other combined therapeutic modes, for example, bacterial resistance for chemotherapy, low drug permeability for PDT/PCT/SDT, adverse immunoreactions for immunotherapy, etc. Admittedly, PTT-derived synergistic treatments are becoming essential in fighting bacterial infection, especially those caused by antibiotic-resistant strains. This review firstly presents the classical and newly reported photothermal agents (PTAs) in brief. Profoundly, through the introduction of delicately designed nanocomposite platforms, we systematically discuss the versatile photothermal-derived multimodal synergistic therapy with the purpose of sterilization application. At the end, challenges to PTT-derived combinational therapy are presented and promising synergistic bactericidal prospects are anticipated.

Hypocrellin Derivative-Loaded Calcium Phosphate Nanorods as NIR Light-Triggered Phototheranostic Agents with Enhanced Tumor Accumulation for Cancer Therapy.

Dopamine modified hypocrellin B (DAHB) derivative-loaded calcium phosphate nanorods (DAHB@CaP NRs) were prepared as a novel phototheranostic agent for effective tumor imaging and therapy. DAHB@CaP NRs were obtained through microwave treatment using DAHB, CaCl2 , NH3 ⋅H2 O, and H3 PO4 as precursors. The DAHB@CaP NRs possessed the following advantages: 1) efficient absorption in the near-infrared (NIR) region from 650 nm to 800 nm; 2) maximum NIR emission at approximately 735 nm; 3) enhanced cellular uptake efficiency in vitro and in vivo; and 4) efficient inhibition of tumor growth and low biotoxicity. These properties indicate the high capability of DAHB@CaP NRs for NIR fluorescence (FL) imaging-guided photodynamic therapy of cancer, thus offering promising new prospects for clinical applications.

Rejuvenated Photodynamic Therapy for Bacterial Infections.

The emergence of multidrug resistant bacterial strains has hastened the exploration of advanced microbicides and antibacterial techniques. Photodynamic antibacterial therapy (PDAT), an old-fashioned technique, has been rejuvenated to combat "superbugs" and biofilm-associated infections owing to its excellent characteristics of noninvasiveness and broad antibacterial spectrum. More importantly, bacteria are less likely to produce drug resistance to PDAT because it does not require specific targeting interaction between photosensitizers (PSs) and bacteria. This review mainly focuses on recent developments and future prospects of PDAT. The mechanisms of PDAT against bacteria and biofilms are briefly introduced. In addition to classical macrocyclic PSs, several innovative PSs, including non-self-quenching PSs, conjugated polymer-based PSs, and nano-PSs, are summarized in detail. Numerous multifunctional PDAT systems such as in situ light-activated PDAT, stimuli-responsive PDAT, oxygen self-enriching enhanced PDAT, and PDAT-based multimodal therapy are highlighted to overcome the inherent defects of PDAT in vivo (e.g., limited penetration depth of light and hypoxic environment of infectious sites).

Pheophytin Derived Near-Infrared-Light Responsive Carbon Dot Assembly as a New Phototheranotic Agent for Bioimaging and Photodynamic Therapy.

Carbon dots (CDs), a kind of phototheranostic agent with the capability of simultaneous bioimaging and phototherapy [i.e., photodynamic therapy (PDT) or photothermal therapy (PTT)], have received considerable attention because of their remarkable properties, including flexibility for surface modification, high biocompatibility, low toxicity and photo-induced activity for malignant tumor cells. Among numerous carbon sources, it has been found that natural biomass are good candidates for the preparation of CD phototheranostic agents. In this study, pheophytin, a type of Mg-free chlorophyll derivative and also a natural product with low toxicity, was used as a raw carbon source for the synthesis of CDs by using a microwave method. The obtained hydrophobic CDs exhibited a maximum near-infrared (NIR) emission peak at approximately 680 nm, and high singlet oxygen (1 O2 ) generation with a quantum yield of 0.62. The self-assembled CDs from the as-prepared CDs with DSPE-mPEG2000 retained efficient 1 O2 generation. The obtained carbon dot assembly was not only an efficient fluorescence (FL) imaging agent but also a smart PDT agent. Our studies indicated that the obtained hydrophilic CD assembly holds great potential as a new phototheranostic agent for cancer therapy. This work provides a new route for synthesis of CDs and proposes a readily available candidate for tumor treatment.

Biodegradable Natural Product-Based Nanoparticles for Near-Infrared Fluorescence Imaging-Guided Sonodynamic Therapy.

Natural products show high potential for clinical translation because of their specific biological activities and molecular structure diversities. Sonosensitizers that originate from natural products play a crucial role as anti-inflammatory and anticancer agents. Herein, hypocrellin-derivative nanoparticles (APHB NPs) were constructed for synchronous near-infrared fluorescence (NIR FL) imaging and sonodynamic therapy (SDT) for deep-seated tumors in vivo. The prepared APHB NPs exhibit excellent water solubility, FL in the NIR region, and effective reactive oxygen species generation under ultrasound stimulation. Furthermore, the APHB NPs show excellent biocompatibility, suitable biodegradation rate, and enhanced tumor accumulation. Therefore, the APHB NPs exhibit promising clinical potential as novel safe and precise NIR FL imaging and SDT agents for deep-seated tumor therapy.

Biodegradable hypocrellin derivative nanovesicle as a near-infrared light-driven theranostic for dually photoactive cancer imaging and therapy.

Photoactive agents based on natural products have attracted substantial attention in clinical applications because of their distinct biological activity, molecular structure multiformity, and low biotoxicity. Herein, we initially modify hypocrellin B (HB) with 1,2-diamino-2-methyl propane to form near-infrared (NIR) light (>700 nm)-responsive amino-substituted HB derivative (DPAHB). The DPAHB exhibit broad absorption (400-800 nm), NIR emission (maximum emission peak at 710 nm), and high singlet oxygen (1O2) quantum yield (∼0.33) under NIR light (721 nm) irradiation. After self-assembly by using DPAHB with PEG-PLGA, the as-prepared nanovesicles (DPAHB NVs) retain efficient 1O2 generation, more interestingly, show high photothermal conversion efficiency (∼0.24) under NIR light (721 nm) irradiation for synergistic photodynamic therapy (PDT) and photothermal therapy toward hypoxic tumor. The DPAHB NVs can not only be as a fluorescence/photoacoustic imaging agent but also exhibit an even stronger PDT efficiency than that of chlorin e6 (a widely used classic photosensitizer). In vitro and in vivo studies demonstrate that DPAHB NVs possess high photothermal stability, enhanced tumor accumulation, and suitable biodegradation rate, thus, show a highly promising clinical potential as a new photoactive agent for cancer therapy.

New detection method for nucleoside triphosphates based on carbon dots: The distance-dependent singlet oxygen trapping.

The distance-dependent based sensing mechanism, such as fluorescence resonance energy transfer (FRET) and surface plasmon resonance (SPR) absorption of gold nanoparticles, has been used widely in visual detection. In this work, we report another distance-dependent detection method for nucleoside triphosphates (NTPs) based on carbon dots (CDs) (1O2 donor) and 9, 10-diphenylanthracene-2-boronic acid (DABA, 1O2 acceptor). The CDs can generate singlet oxygen (1O2) which allows diffusion within 200 nm. Thus, the distance between CDs and DABA decreased through binding of NTPs (<200 nm), leading to absorption changes of DABA under light irradiation due to 1O2 trapping. This sensing system (CDs@DABA) has high selectivity for the detection of NTPs due to the double molecular recognition and a linear response in the 0-80 µM concentration range was accomplished with the detection limit as low as 4.35 µM.

Synthesis of carbon dots from Hypocrella bambusae for bimodel fluorescence/photoacoustic imaging-guided synergistic photodynamic/photothermal therapy of cancer.

As phototheranostic agents, carbon dots (CDs), have recently drawn considerable attention due to their excellent physicochemical properties. However, the complex synthetic route and high-cost of CDs greatly limit their practical application. To address this issue, given their nearly infinite supply from nature, Hypocrella bambusae is used as the precursor for the preparation of CDs in this study. The obtained Hypocrella bambusae CDs (HBCDs) possess good water solubility, broad absorption (350-800 nm), red-light emission (maximum peak at 610 nm), and low biotoxicity. Moreover, HBCDs can highly generate 1O2 (0.38) and heat (27.6%) under 635 nm laser irradiation. These excellent properties of HBCDs capacitate them to be utilized for bimodal fluorescence/photoacoustic imaging-guided synergistic photodynamic therapy (PDT)/photothermal therapy (PTT). This work provides a new candidate for tumor treatment with the combination of PDT and PTT, and explores a novel approach for the preparation of CD-based phototheranostic agents with natural biomass as raw carbon sources.

A Magnetofluorescent Carbon Dot Assembly as an Acidic H2 O2 -Driven Oxygenerator to Regulate Tumor Hypoxia for Simultaneous Bimodal Imaging and Enhanced Photodynamic Therapy.

Recent studies indicate that carbon dots (CDs) can efficiently generate singlet oxygen (1 O2 ) for photodynamic therapy (PDT) of cancer. However, the hypoxic tumor microenvironment and rapid consumption of oxygen in the PDT process will severely limit therapeutic effects of CDs due to the oxygen-dependent PDT. Thus, it is becoming particularly important to develop a novel CD as an in situ tumor oxygenerator for overcoming hypoxia and substantially enhancing the PDT efficacy. Herein, for the first time, magnetofluorescent Mn-CDs are successfully prepared using manganese(II) phthalocyanine as a precursor. After cooperative self-assembly with DSPE-PEG, the obtained Mn-CD assembly can be applied as a smart contrast agent for both near-infrared fluorescence (FL) (maximum peak at 745 nm) and T1 -weighted magnetic resonance (MR) (relaxivity value of 6.97 mM-1 s-1 ) imaging. More interestingly, the Mn-CD assembly can not only effectively produce 1 O2 (quantum yield of 0.40) but also highly catalyze H2 O2 to generate oxygen. These collective properties of the Mn-CD assembly enable it to be utilized as an acidic H2 O2 -driven oxygenerator to increase the oxygen concentration in hypoxic solid tumors for simultaneous bimodal FL/MR imaging and enhanced PDT. This work explores a new biomedical use of CDs and provides a versatile carbon nanomaterial candidate for multifunctional nanotheranostic applications.

Single Near-Infrared Emissive Polymer Nanoparticles as Versatile Phototheranostics.

Attaining consistently high performance of diagnostic and therapeutic functions in one single nanoplatform is of great significance for nanomedicine. This study demonstrates the use of donor-acceptor (D-A) structured polymer (TBT) to develop a smart "all-five-in-one" theranostic that conveniently integrates fluorescence/photoacoustic/thermal imaging and photodynamic/photothermal therapy into single nanoparticle. The prepared nanoparticles (TBTPNPs) exhibit near-infrared emission, high water solubility, excellent light resistance, good pH stability, and negligible toxicity. Additionally, the TBTPNPs exhibit an excellent singlet oxygen (1O2) quantum yield (40%) and high photothermal conversion efficiency (37.1%) under single-laser irradiation (635 nm). Apart from their two phototherapeutic modalities, fluorescence, photoacoustic signals, and thermal imaging in vivo can be simultaneously achieved because of their enhanced permeability and retention effects. This work demonstrates that the prepared TBTPNPs are "all-five-in-one" phototheranostic agents that can exhibit properties to satisfy the "one-fits-all" requirement for future phototheranostic applications. Thus, the prepared TBTPNPs can provide fundamental insights into the development of PNP-based nanoagents for cancer therapy.