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Background: Tumor phototherapy especially photodynamic therapy (PDT) or photothermal therapy (PTT), has been considered as an attractive strategy to elicit significant immunogenic cell death (ICD) at an optimal tumor retention of PDT/PTT agents. Heptamethine cyanine dye (IR-780), a promising PDT/PTT agent, which can be used for near-infrared (NIR) fluorescence/photoacoustic (PA) imaging guided tumor phototherapy, however, the strong hydrophobicity, short circulation time, and potential toxicity in vivo hinder its biomedical applications. To address this challenge, we developed mesoporous polydopamine nanoparticles (MPDA) with excellent biocompatibility, PTT efficacy, and PA imaging ability, facilitating an efficient loading and protection of hydrophobic IR-780. Results: The IR-780 loaded MPDA (IR-780@MPDA) exhibited high loading capacity of IR-780 (49.7 wt%), good physiological solubility and stability, and reduced toxicity. In vivo NIR fluorescence and PA imaging revealed high tumor accumulation of IR-780@MPDA. Furthermore, the combined PDT/PTT of IR-780@MPDA could induce ICD, triggered immunotherapeutic response to breast tumor by the activation of cytotoxic T cells, resulting in significant suppression of tumor growth in vivo. Conclusion: This study demonstrated that the as-developed compact and biocompatible platform could induce combined PDT/PTT and accelerate immune activation via excellent tumor accumulation ability, offering multimodal tumor theranostics with negligible systemic toxicity. [ABSTRACT FROM AUTHOR]

Inorganic nanomaterials with intrinsic singlet oxygen (1O2) generation capacity, are emerged yet dynamically developing materials as nano‐photosensitizers (NPSs) for photodynamic therapy (PDT). Compared to previously reported nanomaterials that have been used as either carriers to load organic PSs or energy donors to excite the attached organic PSs through a Foster resonance energy transfer process, these NPSs possess intrinsic 1O2 generation capacity with extremely high 1O2 quantum yield (e.g., 1.56, 1.3, 1.26, and 1.09) than any classical organic PS reported to date, and thus are facilitating to make a revolution in PDT. In this review, the recent advances in the development of various inorganic nanomaterials as NPSs, including metal‐based (gold, silver, and tungsten), metal oxide‐based (titanium dioxide, tungsten oxide, and bismuth oxyhalide), metal sulfide‐based (copper and molybdenum sulfide), carbon‐based (graphene, fullerene, and graphitic carbon nitride), phosphorus‐based, and others (hybrids and MXenes‐based NPSs) are summarized, with an emphasis on the design principle and 1O2 generation mechanism, and the photodynamic therapeutic performance against different types of cancers. Finally, the current challenges and an outlook of future research are also discussed. This review may provide a comprehensive account capable of explaining recent progress as well as future research of this emerging paradigm. [ABSTRACT FROM AUTHOR]

The aim of this work is to evaluate the role of viscosity of the organic condensate obtained from fast pyrolysis of wheat straw. Based on the experimental data, a model has been developed that is able to adequately describe the viscosity as a function of relevant process parameters. The developed model is helpful to investigate the reduction of heat transfer in the heat exchangers of the organic condensate cycle when glycol is replaced by an organic condensate. Temperature, solid contents, and water contents play a significant role and affect the viscosity of bio-oil. As temperature increases, the viscosity of oil reduces rapidly. Viscosity-temperature profile follows an Arrhenius-type-relationship, where the viscosity of the bio-oil decreases exponentially with increasing temperature. As solid content increases, exponential increase of viscosity takes place. However, the increase in water content results in decrease of viscosity on logarithmic scale. The range of water addition in organic condensate is possible up to a certain limit, after certain limit it starts to separate out in two phases. Investigation of reduction of heat transfer in heat exchanger shows that Nusselt number decreases with the increase of viscosity. Therefore, the overall heat transfer coefficient will decrease in case of organic condensate as compared to glycol. [ABSTRACT FROM AUTHOR]

Dendrimers have numerous applications in imaging and drug delivery. Designing a dendrimer diagnostic platform with a well-defined structure and controlled drug delivery is a formidable challenge. Here, we design dendritic polymer-platinum conjugates (G5-PEG-Pt) as pH-responsive nanovesicles for imaging-guided platinum drug delivery. The G5-PEG-Pt have a well-defined structure, intrinsically bright fluorescence, and acid-responsive drug release. The pH-responsive G5-PEG-Pt could rapidly release the platinum drug at acidic pH (5.0) than neutral pH (7.4). The G5-PEG-Pt could enter SKOV-3 human ovarian cancer cells by the endocytosis pathway and exhibited comparative cytotoxicity to free cisplatin. By virtue of the prolonged blood circulation time and the enhanced permeability and retention (EPR) effect, a 4.4-fold higher tumor platinum uptake than that of free cisplatin was achieved, potentially enhancing the therapeutic indexes of the platinum drug. Therefore, these pH-responsive platinum and fluorescent dendrimer conjugates are expected to be potent in vivo cancer optical imaging and therapy platforms. [Display omitted] • The fluorescent dendritic polymer-platinum conjugates (G5-PEG-Pt) were prepared. • G5-PEG-Pt can be used for imaging-guided platinum drug delivery. • G5-PEG-Pt can rapidly release platinum under the acidic environment. • G5-PEG-Pt with prolonged blood circulation can efficiently accumulate into tumor. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a kind of kidney disease with a high mortality rate, and is predominantly associated with abundant endogenous reactive oxygen/nitrogen species (RONS). However, there are no universal clinical treatment options currently. Development of antioxidants with high kidney enrichment is highly desired to prevent AKI. As a promising new artificial enzyme, nanozymes have attracted extensive attention over the past decade because of their commendable advantages over natural and traditional artificial enzymes. In this study, we reported ultrasmall polyvinylpyrrolidone-coated iridium nanoparticles (denoted as Ir NPs-PVP, 1.5 nm) as multi-enzyme mimetic to scavenge a variety of RONS, offering an efficient RONS-induced cellular protection. Meanwhile, computed tomography and inductively coupled plasma mass spectrometry demonstrated preferential renal uptake of Ir NPs-PVP following intravenous administration, leading to alleviate clinical symptoms in mice subjected to rhabdomyolysis- or cis-platinum-induced AKI. Impressively, ultrasmall Ir NPs-PVP exhibit relatively low systemic side effects in vivo due to rapid renal clearance via urine. Our work presents the clinically translatable potential of ultrasmall nanozymes for AKI management. [Display omitted] [ABSTRACT FROM AUTHOR]

Intrauterine adhesions (IUAs) caused by mechanical damage or infection increase the risk of infertility in women. Although numerous physical barriers such as balloon or hydrogel are developed for the prevention of IUAs, the therapeutic efficacy is barely satisfactory due to limited endometrial healing, which may lead to recurrence. Herein, a second near‐infrared (NIR‐II) light‐responsive shape memory composite based on the combination of cuprorivaite (CaCuSi4O10) nanosheets (CUP NSs) as photothermal conversion agents and polymer poly(d,l‐lactide‐co‐trimethylene carbonate) (PT) as shape memory building blocks is developed. The as‐prepared CUP/PT composite possesses excellent shape memory performance under NIR‐II light, and the improved operational feasibility as an antiadhesion barrier for the treatment of IUAs. Moreover, the released ions (Cu, Si) can stimulate the endometrial regeneration due to the angiogenic bioactivity. This study provides a new strategy to prevent IUA and restore the injured endometrium relied on shape memory composite with enhanced tissues reconstruction ability. [ABSTRACT FROM AUTHOR]

Background: Sonodynamic therapy (SDT) has emerged as a noninvasive therapeutic modality that involves sonosensitizers and low-intensity ultrasound. However, owing to the rapid recombination of charge carriers, most of the sonosensitizers triggered poor reactive oxygen species (ROS) generation, resulting in unsatisfactory sonodynamic therapeutic effects. Results: Herein, a photo/sono-responsive nanoplatform was developed through the in-situ systhesis of TiO2-x on the surface of two-dimensional MXene (titanium carbide, Ti3C2) for photoacoustic/photothermal bimodal imaging-guided near-infrared II (NIR-II) photothermal enhanced SDT of tumor. Because of several oxygen vacancies and smaller size (~ 10 nm), the in-situ formed TiO2-x nanoparticles possessed narrow band gap (2.65 eV) and high surface area, and thus served as a charge trap to restrict charge recombination under ultrasound (US) activation, resulting in enhanced sonodynamic ROS generation. Moreover, Ti3C2 nanosheets induced extensive localized hyperthermia relieves tumor hypoxia by accelerating intratumoral blood flow and tumor oxygenation, and thus further strengthened the efficacy of SDT. Upon US/NIR-II laser dual-stimuli, Ti3C2@TiO2-x nanoplatform triggered substantial cellular killing in vitro and complete tumor eradication in vivo, without any tumor recurrence and systemic toxicity. Conclusion: Our work presents the promising design of photo/sono-responsive nanoplatform for cancer nanotheranostics. [ABSTRACT FROM AUTHOR]

Patients with diabetes mellitus (DM) suffer from a high risk of fractures and poor bone healing ability. Surprisingly, no effective therapy is available to treat diabetic bone defect in clinic. Here, a 3D printed enzyme‐functionalized scaffold with multiple bioactivities including osteogenesis, angiogenesis, and anti‐inflammation in diabetic conditions is proposed. The as‐prepared multifunctional scaffold is constituted with alginate, glucose oxidase (GOx), and catalase‐assisted biomineralized calcium phosphate nanosheets (CaP@CAT NSs). The GOx inside scaffolds can alleviate the hyperglycemia environment by catalyzing glucose and oxygen into gluconic acid and hydrogen peroxide (H2O2). Both the generated H2O2 as well as the overproduced H2O2 in DM can be scavenged by CaP@CAT NSs, while the initiated hypoxic microenvironment stimulates neovascularization. Moreover, the incorporation of CaP@CAT NSs not only enhance the mechanical property of the scaffolds, but also facilitate bone regeneration by the degraded Ca2+ and PO43− ions. The remarkable in vitro and in vivo outcomes demonstrate that enzymes functionalized scaffolds can be an effective strategy for enhancing bone tissue regeneration in diabetic conditions, underpinning the potential of multifunctional scaffolds for diabetic bone regeneration. [ABSTRACT FROM AUTHOR]

Nanochannel/nanopre based analysis methods have attracted increasing interest in recent years due to their exquisite ability to reveal changes in molecular volume. In this work, a highly asymmetric nanochannel-ionchannel hybrid coupled with an electrochemical technique was developed for copper ion (Cu2+) detection. Polyglutamic acid (PGA) was modified in a nanochannel array of porous anodic alumina (PAA). When different concentrations of Cu2+ were introduced into the nanochannel-ionchannel hybrid in a neutral environment, a Cu2+-PGA chelation reaction occurs, resulting in varied current-potential (I-V) properties of the nanochannel-ionchannel hybrid. When PAA was immersed in a low pH solution, the Cu2+-PGA complex dissociated. On the basis of the change in ionic current, a label-free assay for Cu2+ was achieved along with the ability to regenerate and reuse the constructed platform. Because of the unique mass transfer property of the nanochannel-ionchannel hybrid combined with the highly amplified ionic current magnitude of the nanochannel array, significantly increased assay sensitivity was achieved, as expected. To evaluate the applicability of the present methodology for detecting Cu2+ in a real sample, the Cu2+ content in real blood samples was analyzed. The results demonstrate that the present method shows excellent selectivity with high sensitivity toward Cu2+ detection in real blood samples. [ABSTRACT FROM AUTHOR]

With the growing demands of the early, accurate, and sensitive diagnosis for cancers, the development of new diagnostic technologies becomes increasingly important. In this study, we proposed a strategy for efficient capture and sensitive detection of circulating tumor cells (CTCs) using an array nanochannel-ion channel hybrid coupled with an electrochemical detection technique. The aptamer probe was immobilized on the ion channel surface to couple with the protein overexpressed on the CTCs membrane. Through this special molecular recognition, CTCs can be selectively captured. The trapped CTCs cover the ion channel entrance efficiently, which will dramatically block the ionic flow through channels, resulting in a varied mass-transfer property of the nanochannel-ion channel hybrid. On the basis of the changed mass-transfer properties, the captured CTCs can be sensitively detected using the electrochemical linear sweep voltammetry technique. Furthermore, due to the amplified response of array channels compared to that of a single channel, the detection sensitivity can be enhanced greatly. The results showed that acute leukemia CCRF-CEM (a type of CTC) concentration as low as 100 cells mL-1 can be successfully captured and detected. The present method provides a simple, sensitive, and label-free technique for CTCs capture, detection, and release, which would hold great potential in the early clinical diagnosis and treatment of cancers. [ABSTRACT FROM AUTHOR]

We present a second near‐infrared (NIR‐II) self‐checking molecule, LET‐1052, for acidic tumor microenvironment (TME) turn‐on photothermal therapy (PTT), followed by viscosity based therapeutic efficacy evaluation by itself in two independent channels, denoted as "self‐checking" strategy. In acidic TME, LET‐1052 was protonated and turned on NIR‐II absorption for PTT under 1064 nm laser irradiation. Subsequently, PTT‐induced cellular death increases intracellular viscosity, which inhibited the intramolecular rotation of LET‐1052, resulting in the enhancement of NIR‐I fluorescence for real‐time evaluation of PTT efficacy. After PTT of tumor‐bearing mice for different periods of NIR‐II laser irradiation, NIR‐I fluorescence in the tumor region showed positive correlation with tumor growth inhibition rate, demonstrating reliable and prompt prediction of PTT efficacy. The strategy may be expanded for instant evaluation of other therapeutic modalities for personalized medicine. [ABSTRACT FROM AUTHOR]

We present a second near‐infrared (NIR‐II) self‐checking molecule, LET‐1052, for acidic tumor microenvironment (TME) turn‐on photothermal therapy (PTT), followed by viscosity based therapeutic efficacy evaluation by itself in two independent channels, denoted as "self‐checking" strategy. In acidic TME, LET‐1052 was protonated and turned on NIR‐II absorption for PTT under 1064 nm laser irradiation. Subsequently, PTT‐induced cellular death increases intracellular viscosity, which inhibited the intramolecular rotation of LET‐1052, resulting in the enhancement of NIR‐I fluorescence for real‐time evaluation of PTT efficacy. After PTT of tumor‐bearing mice for different periods of NIR‐II laser irradiation, NIR‐I fluorescence in the tumor region showed positive correlation with tumor growth inhibition rate, demonstrating reliable and prompt prediction of PTT efficacy. The strategy may be expanded for instant evaluation of other therapeutic modalities for personalized medicine. [ABSTRACT FROM AUTHOR]

[Display omitted] • A facile strategy was developed for shape memory composite (SMC). • CaSiCu 4 O 10 (CUP) nanosheets exhibited good NIR-II photothermal activity. • SMC with CUP offered remote actuation and enhanced tissue reconstruction. • The release of Cu2+ and SiO 4 4- ions from CUP could accelerate wound healing. Near-infrared (NIR) light-responsive shape-memory composites have shown great potential in various biomedical applications due to their amazing remote actuation property. However, most of them are bioinert and restricted in NIR-I biological window. Here, we developed a new biodegradable NIR-II-responsive shape memory composite by the incorporation of CaSiCu 4 O 10 nanosheets (CUP NSs) into shape memory polymer of poly (D, L-lactide-co-trimethylene carbonate) (PDLLA-co-TMC, denoted as PT). The as-prepared CUP/PT composites possessed outstanding shape memory performance upon low power NIR-II laser irradiation (1064 nm, 0.4 W·cm−2), offering the possibility of deep-tissue applications. Moreover, due to the sustained release of bioactive Cu2+ and SiO 4 4- ions, the composites exhibited strong stimulation of angiogenesis both in vitro and in vivo. Our work demonstrated the promising potential of CUP/PT composites as NIR-II light-responsive biomaterials with enhanced tissue reconstruction ability, especially for wound healing. [ABSTRACT FROM AUTHOR]

There are no significant differences between the control group and GOx contained groups, indicating the long-term biosafety of GOx contained scaffolds in vivo. 3D Printed Enzyme-Functionalized Scaffold Facilitates Diabetic Bone Regeneration The original image of lung in the Alg/GOx group was repeatedly clipped and used again in Figure S12 (Supporting information) for the Alg/GOx/CaP@CAT group in error. [Extracted from the article]

Various bifunctional scaffolds have recently been developed to address the reconstruction of tumor‐initiated bone defects. Such scaffolds are usually composed of a near‐infrared (NIR) photothermal conversion agent and a conventional bone scaffold for photothermal therapy (PTT) and long‐term bone regeneration. However, the reported photothermal conversion agents are mainly restricted to the first biological window (NIR‐I) with intrinsic poor tissue penetration depth. Also, most of these agents are non‐bioactive materials, which induced potential systemic side toxicity after implantation. Herein, a NIR‐II photothermal conversion agent (Wesselsite [SrCuSi4O10] nanosheets, SC NSs) with tremendous osteogenic and angiogenic bioactivity, is rationally integrated with polycaprolactone (PCL) via 3D printing. The as‐designed 3D composite scaffolds not only trigger osteosarcoma ablation through NIR‐II light generated extensive hyperthermia, but also promote in vitro cellular proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) and human umbilical vein endothelial cells (HUVECs), respectively, and the ultimate enhancement of vascularized bone regeneration in vivo owing to the controlled and sustained release of bioactive ions (Sr, Cu, and Si). The authors' study provides a new avenue to prepare multifunctional bone scaffolds based on therapeutic bioceramics for repairing tumor‐induced bone defects. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) with high mortality rates is associated with an excess of reactive oxygen/nitrogen species (RONS) within kidney tissues. Recently, nanomedicine antioxidant therapy has been used to alleviate AKI. Herein, we synthesized ultrasmall Prussian blue nanozymes (PB NZs, 4.5 nm) as theranostic agents for magnetic resonance (MR)/photoacoustic (PA) dual-modal imaging guided AKI treatment. Results: PB NZs exhibited multi-enzyme mimetic abilities, promoting the effective elimination of RONS both in vitro and in vivo. Moreover, benefiting from their imaging contrast properties, the rapid renal accumulation of PB NZs was verified by in vivo PA/MR dual-modal imaging. Due to their excellent enrichment in the kidney and unique multi-enzyme mimetic abilities, ultrasmall PB NZs displayed superior AKI treatment efficacy compared with that of amifostine in two clinically relevant types of AKI induced murine models (either by rhabdomyolysis or cisplatin). Conclusion: Our findings suggested ultrasmall PB NZs, as nanozyme theranostics, have great potential for AKI management. [ABSTRACT FROM AUTHOR]

• Ultrasmall platinum nanoparticles are prepared as multienzyme mimetics. • Pt nanozymes exhibit preferential kidneys enrichment and rapid clearance from the body. • Pt nanozymes facilitate effective removal of a variety of RONS. • Pt nanozymes promise PA/CT dual-modal imaging guided treatment of AKI. Acute kidney injury (AKI) is a common kidney disease with high mortality rate, while surprisingly, the supportive treatment and renal replacement are the only available clinical treatment options to date. The onset of AKI is often triggered by excessive toxic reactive oxygen/nitrogen species (RONS), and hence, the development of antioxidants with high renal accumulation and effective renal clearance is highly demanded to consume RONS in the kidneys. In this study, we developed ultrasmall polyvinylpyrrolidone-coated platinum nanoparticles (Pt NPs-PVP, ~3 nm) as multienzyme mimetics (catalase, peroxidase, and superoxide dismutase). Thanks to their excellent RONS scavenging ability, Pt NPs-PVP effectively reduced the hydrogen peroxide induced cellular damage. Analytical (inductively coupled plasma mass spectrometry) as well as imaging (photoacoustic and computed tomography) techniques revealed the preferential renal uptake and high enrichment of ultrasmall Pt NPs-PVP after intravenous administration, offering remarkable relief of the clinical symptoms of glycerol-induced AKI mice without any apparent systemic toxicity in vivo. Importantly, because of their ultrasmall size, Pt NPs-PVP exhibited rapid excretion from healthy mice, presenting relatively low toxicity and side effects. In conclusion, our work demonstrated ultrasmall Pt nanozyme as a state of the art antioxidant for dual-modal imaging guided treatment of AKI with improved treatment efficacy. [ABSTRACT FROM AUTHOR]

• 3D printed PCL/CS scaffolds were developed with excellent bioactive compositions and controllable porous structures. • Alkaline phosphatase (ALP)-responsive scaffolds were developed through the combination of a hemicyanine dye and PCL/CS scaffolds. • The combination of near-infrared (NIR) fluorescence and photoacoustic imaging was achieved. • Non-invasive, real-time visualization of enhanced bone formation was achieved both in vitro and in vivo. Although numerous biomaterials have been fabricated as scaffolds for the application of tissue engineering, real-time non-invasive monitoring of in vivo bone regeneration is still a big challenge. Particularly, the early osteogenesis is difficult to detect using conventional imaging modalities, such as X-ray computed tomography (CT) and magnetic resonance imaging (MRI) due to the limited amount of neo-bone tissue. Herein we report on alkaline phosphatase (ALP)-responsive scaffolds, which are composed of a turn-on hemicyanine dye (LET-3) and a typical three dimensional (3D) printed bone tissue engineering scaffold (polycaprolactone/calcium silicate, PCL/CS), for real-time non-invasive monitoring of in vivo bone regeneration by near-infrared fluorescence (NIR-FL) and photoacoustic (PA) duplex imaging. ALP, an early-stage biomarker of bone formation, turns "on" the NIR-FL/PA signals of LET-3 in scaffolds both in vitro and in vivo. Thus, the osteogenic-associated bioactivity of LET-3 labeled scaffolds could be visualized by NIR-FL/PA dual-modal imaging. Our results provide a promising strategy for detecting neo-bone formation by the combination of ALP prober and bone tissue engineering scaffolds, which holds great potential for traceable tissue engineering. [ABSTRACT FROM AUTHOR]

• A dual emissive fluorescent nano aptasensor of CDs and CdTe/CdS/ZnS QDs was designed for simultaneous detection of human serum glucose and insulin levels. • All the reaction parameters were optimized and a polynomial regression model was constructed to explain the effects of reaction parameters. • The probe was validated and applied successfully to the determination of the stated analytes in human serum. A dual emissive fluorescent nano aptasensor was designed for simultaneous detection of human serum glucose and insulin levels. CdTe/CdS/ZnS quantum dots and carbon dots were synthesized and conjugated with the aptamers of glucose and insulin, respectively. The fluorescence of these conjugates was quenched by nano-graphite based on the static quenching and inner filter effect, and restored on the addition of the analytes. All reaction parameters were optimized using analysis of variance, and a polynomial regression model was constructed and verified to explain the effects of reaction parameters on the outcome. The linear ranges of insulin and glucose were 0.2–2 nM and 0.5–7 mM, respectively. The limits of detection for insulin and glucose were 0.018 nM and 0.058 mM, respectively. All the values of relative error % were within the range of −5.00−4.00%, and the values of relative standard deviation % were ≤3.77%. The changes in fluorescence intensity restoration of the probe in the presence of various interfering species were less than 5%, and all the recoveries for glucose and insulin were in the range of 90–110%. The probe was validated and applied successfully to the determination of the stated analytes in human serum. The fabricated aptasensor can be used to diagnose diabetes and its type with a single assay in clinical diagnostic labs. [ABSTRACT FROM AUTHOR]

Type 2 diabetes is a metabolic disorder in which the patient fails to control the glycemic level due to compromised functioning of pancreatic α and β cells. The control of these cells is regulated by the extent of incretin peptides (GLP1 and GIP). Performance of these peptides is affected due to the increased degradation by di-peptidyl-peptidase-4 (DPP-4) enzyme in diabetic patients. Vildagliptin (VL) is one of the potential DPP-4 inhibitors and helps in controlling the glycemic level, but to deliver the VL near its site of action (intestine and blood) in a sustained manner is important. For this purpose, we used chitosan (Chit) (cationic polymer) to coat the VL-loaded DNA rectangles (negatively charged) via electrostatic attractions to make Chit-DNA-VL nanospheres. According to our results, nanospheres formulated by this novel approach were uniformed, spherical, and stable with better size control (from 40 to 400 nm in diameter). Entrapment efficiency for VL drug was up to 85%. The release of VL was extended up to 12 ± 5 h. From observed incretin and glycemic level, we concluded that the nanospheres efficiently bypassed the gastric acidity improving glycemic control in Db-Db/mouse model. Histological experiments revealed Chit-DNA-VL nanospheres did not cause damage to pancreas associated with the sustained and prolonged release of VL. [ABSTRACT FROM AUTHOR]