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Gold nanorods (GNRs) with a unique localized surface plasmon resonance (LSPR) property have shown groundbreaking performance in catalysis, sensing, and biomedical applications. Intrinsic inertness, biocompatibility, a tunable longitudinal LSPR band in the near‐infrared (NIR)‐I/II region, high extinction coefficient, and remarkable optical properties all make GNRs excellent photothermal (PT) nanoagents, photosensitizers, and imaging contrast agents for drug delivery, cancer phototherapy, and multimodal imaging‐guided cancer therapy. In this periodic update, bottom–up fabrication of long and short GNRs by seed‐mediated and seedless methods is reviewed, with elaboration concerning the tuning of LSPR band and the generation of localized hyperthermia via light to heat conversion. Recent advances in applications of GNR research in bioimaging, therapy, and theranostics of cancer are then reviewed. Unmet challenges and critical points are discussed with focus given to translation from bench to clinic. Gold nanorods (GNRs), 1D plasmonic material, possess tunable localized surface plasmon band, excellent photostability, high absorption cross section, and extinction coefficient. These fascinating physiochemical features endow GNRs with promising biomedical potential for efficient tumor diagnosis through PT/photoacoustic imaging, reactive oxygen species/thermal ablation‐mediated antitumor photodynamic/PT therapy, and simultaneous tumor diagnosis and treatment.

5-Aminolevulinic acid-based photodynamic therapy heavily depends on the biological transformation efficiency of 5-aminolevulinic acid to protoporphyrin IX, while the lack of an effective delivery system and imaging navigation are major hurdles in improving the accumulation of protoporphyrin IX and optimizing therapeutic parameters. Herein, we leverage a synthetic biology approach to construct a transdermal theranostic microneedle patch integrated with 5-aminolevulinic acid and catalase co-loaded tumor acidity-responsive copper-doped calcium phosphate nanoparticles for efficient 5-aminolevulinic acid-based photodynamic therapy by maximizing the enrichment of intratumoral protoporphyrin IX. We show that continuous oxygen generation by catalase in vivo reverses tumor hypoxia, enhances protoporphyrin IX accumulation by blocking protoporphyrin IX efflux (downregulating hypoxia-inducible factor-1α and ferrochelatase) and upregulates protoporphyrin IX biosynthesis (providing exogenous 5-aminolevulinic acid and upregulating ALA-synthetase). In vivo fluorescence/photoacoustic duplex imaging can monitor intratumoral oxygen saturation and protoporphyrin IX metabolic kinetics simultaneously. This approach thus facilitates the optimization of therapeutic parameters for different cancers to realize Ca 2+ /Cu 2+ -interferences-enhanced repeatable photodynamic therapy, making this theranostic patch promising for clinical practice. An effective delivery system and imaging method for 5-Aminolevulinic acid (5-ALA)-based photodynamic therapy facilitated by the conversion of 5-ALA to protoporphyrin IX (PpIX) are lacking. Here, reversing the hypoxic tumour microenvironment can increase the in vivo biosynthesis of PpIX through the regulation of PpIX-related synthetases for traceable photodynamic therapy.

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. Inorganic nano‐photosensitizers possess higher extinction coefficient, resistance to photobleaching, larger absorption cross‐section, and high singlet oxygen quantum yield than their organic counterparts. These fascinating physiochemical features endow them with promising potential for reactive oxygen species‐mediated photodynamic tumor cell killing, antibacterial therapy, thermal ablation‐induced antitumor photothermal therapy, and simultaneous tumor diagnosis and treatment for multimodal cancer theranostics.

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. An efficient multifunctional bone scaffold based on 3D printed SrCuSi4O10 nanosheets/polycaprolactone composite is developed as SC/PCL, which possesses excellent therapeutic effects for deep‐seated osteosarcoma due to its high photothermal‐conversion efficiency in the second biological window. Moreover, the as‐designed 3D composite scaffold could facilitate the vascularized bone regeneration via the sustained release of bioactive ions (Sr, Si, and Cu).

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 TiO 2-x on the surface of two-dimensional MXene (titanium carbide, Ti 3 C 2 ) 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 TiO 2-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, Ti 3 C 2 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, Ti 3 C 2 @TiO 2-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. Graphical Abstract

Acute kidney injury (AKI) is associated with aberrant generation of oxidative species and inflammation, leading to high mortality of in-hospitalized patients. Although -acetylcysteine (NAC) showed positive effects in alleviating contrast-induced AKI, the clinical applications are strongly restrained due to the low bioavailability, low renal accumulation, short renal retention time, and high dosage-induced toxicity. We addressed the clinical dilemma of NAC by developing ultrasmall gold nanoclusters (1-2 nm) capped with NAC (denoted as Au NCs-NAC) as a nanozyme-based antioxidant defense system for AKI alleviation. Rhabdomyolysis-induced AKI mice model was developed, and the same dose of free NAC (as a control) and NAC onto Au NCs (Au NCs-NAC) was used for investigation of AKI restoration. The as-developed gold nanozyme exhibited high bioavailability and good physicochemical stability as compared to NAC. Meanwhile, Au NCs-NAC showed broad-spectrum antioxidant activity of Au NCs-NAC, offering renoprotective effects, as well as macrophages by relieving inflammation under hydrogen peroxide or lipopolysaccharide stimulation. Notably, owing to the smaller size than kidney threshold (5.5 nm), Au NCs-NAC displayed preferential renal enrichment (< 2 h) and longer retention (> 24 h) in AKI mice as revealed by fluorescence imaging, thereby largely enhancing the restoration of renal function in AKI mice than free NAC by protecting the kidneys from oxidative injury and inflammation without systemic toxicity, as demonstrated by tissues staining, inflammatory cytokines and biomarkers detection, and mice survival rate. Owing to the synergistic anti-inflammatory/antioxidative effects, and enhanced bioavailability and renal accumulation/retention, Au NCs-NAC displayed far superior therapeutic performance than NAC alone. This work will facilitate the development of high-performance antioxidative nanoplatforms, as well as overcome the clinical limitations of small molecular drugs for AKI treatment and other inflammatory diseases.

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. Graphical Abstract

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. Graphic abstract

Wind is an important renewable energy source. The majority of wind farms in Pakistan are installed in Jhimpir, Sindh Wind Corridor. At this location, downstream turbines encounter upstream turbines’, wake, decreasing power output. To maximize the power output, there is a need to minimize these wakes. In this research, a method is proposed to maximize the power output using a Genetic Algorithm (GA). Hub heights and inter-turbine spacing are considered variables in this method. Two wind farms located at Jhimpir, Sindh, namely, Second and Third Three Gorges Wind Farms (TGWFs), have been analyzed. Three different cases are considered to maximize the power output. In Case 1, thesame hub heights and inter-turbine spacing without wake effects are considered. In Case 2, the same hub heights and inter-turbine spacing with wake effects are considered. In Case 3, variable hub heights and inter-turbine spacing with wake effects are considered. The results revealed that TGWFs, with variable hub heights and inter-turbine spacing, produce more power output. It is also revealed that the increase in power output, in the case of two different hub heights, is greater in comparison to three different hub heights. Eventually, the proposed method may help in the layout optimization of a wind farm.

Timely and effective interventions after tracheal mucosal injury are lack in clinical practices, which elevate the risks of airway infection, tracheal cartilage deterioration, and even asphyxiated death. Herein, we proposed a biomaterial-based strategy for the repair of injured tracheal mucosal based on a copper hydrogen phosphate nanosheets (CuHP NSs) functionalized commercial hydrogel (polyethylene glycol disuccinimidyl succinate-human serum albumin, PH). Such CuHP/PH hydrogel achieved favorable injectability, stable gelation, and excellent adhesiveness within the tracheal lumen. Moreover, CuHP NSs within the CuHP/PH hydrogel effectively stimulate the proliferation and migration of endothelial/epithelial cells, enhancing angiogenesis and demonstrating excellent tissue regenerative potential. Additionally, it exhibited significant inhibitory effects on both bacteria and bacterial biofilms. More importantly, when injected injured site of tracheal mucosa under fiberoptic bronchoscopy guidance, our results demonstrated CuHP/PH hydrogel adhered tightly to the tracheal mucosa. The therapeutic effects of the CuHP/PH hydrogel were further confirmed, which significantly improved survival rates, vascular and mucosal regeneration, reduced occurrences of intraluminal infections, tracheal stenosis, and cartilage damage complications. This research presents an initial proposition outlining a strategy employing biomaterials to mitigate tracheal mucosal injury, offering novel perspectives on the treatment of mucosal injuries and other tracheal diseases.