A Poloxamer 407/chitosan-based thermosensitive hydrogel dressing for diabetic wound healing via oxygen production and dihydromyricetin release.

The current clinical treatment of diabetic wounds is still based on oxygen therapy, and the slow healing of skin wounds due to hypoxia has always been a key problem in the repair of chronic skin injuries. To overcome this problem, the oxygen-producing matrix CaO2NPS based on the temperature-sensitive dihydromyricetin-loaded hydrogel was prepared. In vitro activity showed that the dihydromyricetin (DHM) oxygen-releasing temperature-sensitive hydrogel composite (DHM-OTH) not only provided a suitable oxygen environment for cells around the wound to survive but also had good biocompatibility and various biological activities. By constructing a T2D wound model, we further investigated the repairing effect of DHM-OTH on chronic diabetic skin wounds and the mechanisms involved. DHM-OTH was able to reduce inflammatory cells and collagen deposition and promote angiogenesis and cell proliferation for diabetic wound healing. These in vitro and in vivo data suggest that DHM-OTH accelerates diabetic wound repair as a novel method to efficiently deliver oxygen to wound tissue, providing a promising strategy to improve diabetic wound healing.

Responsive manganese-based nanoplatform amplifying cGAS-STING activation for immunotherapy.

BACKGROUND: The activation of the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) signaling pathway has attracted great attention for its ability to up-regulate innate immune response and thus enhance cancer immunotherapy. However, many STING agonists limit the further advancement of immunotherapy due to weak tumor responsiveness or low activation efficiency. The responsive and effective activation of cGAS-STING signaling in tumors is a highly challenging process. METHODS: In this study, a manganese-based nanoplatform (MPCZ NPs) was constructed that could responsively and efficiently generate more manganese ions (Mn2+) and reactive oxygen species (ROS) to activate cGAS-STING signaling pathway. Briefly, manganese dioxide (MnO2) was loaded with zinc protoporphyrin IX (ZPP) molecule and coated by polydopamine (PDA) embedded with NH4HCO3 to obtain MPCZ NPs. Additionally, MPCZ NPs were evaluated in vitro and in vivo for their antitumor effects by methyl thiazolyl tetrazolium (MTT) assay and TUNEL assays, respectively. RESULTS: In this system, tumor responsiveness was achieved by exogenous (laser irradiation) and endogenous (high levels GSH) stimulation, which triggered the collapse or degradation of PDA and MnO2. Moreover, the release of Mn2+ augmented the cGAS-STING signaling pathway and enhanced the conversion of hydrogen peroxide (H2O2) to hydroxyl radical (·OH) under NIR laser irradiation. Furthermore, the release of ZPP and the elimination of GSH by MPCZ NPs inhibited HO-1 activity and prevented ROS consumption, respectively. CONCLUSIONS: This adopted open source and reduce expenditure strategy to effectively generate more ROS and Mn2+ to responsively activate cGAS-STING signaling pathway, providing a new strategy for improving immunotherapy.

Upregulation of MHC-I and downregulation of PD-L1 expression by doxorubicin and deferasirox codelivered liposomal nanoparticles for chemoimmunotherapy of melanoma.

Tumor immunotherapy is a promising strategy to activate the immune system and eliminate tumors. Major histocompatibility complex I (MHC-I) is usually applied to potentiate antigen presentation, but it is associated with upregulation of programmed death ligand 1 (PD-L1) expression, which is unfavorable for activation of immune responses. Moreover, poor permeability of various therapeutic antibodies results in the limited immune response rates of most patients. It is necessary to develop combined small molecule drug delivery systems for simultaneous upregulation of MHC-I expression and downregulation of PD-L1 expression, promoting effective tumor treatment. A moderate dose of doxorubicin hydrochloride (DOX) can induce upregulation of MHC-I expression, while deferasirox (DFX) can inhibit the PI3K-Akt pathway, which potentially downregulates PD-L1 expression. In the present study, we designed a pH-sensitive liposome to incorporate DOX in the hydrophilic cavity and embed DFX in the hydrophobic shell, forming a dual delivery system (DOX-DFXL). In a B16F10 melanoma-bearing mouse model, DOX and DFX were released in acidic tumor microenvironment, which further lead to enhanced antigen presentation and infiltration of T cells into tumor tissues as a result of tumor remission. This codelivery system holds great potential for clinical applications of tumor immunotherapy.

Property-activity relationship between physicochemical properties of PM2.5 and their activation of NLRP3 inflammasome.

Air pollution is becoming severe environment factor affecting human health. More and more research has indicated that fine particulate matter (PM2.5) plays a critical role in causing pulmonary inflammation or fibrosis, which potentially is ascribed to the activation of nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome. However, the underlying property-activity relationship between the physicochemical properties of PM2.5 and their activation of NLRP3 inflammasome remains unclear. Herein, various ways, such as metal chelation, organic extraction, ROS consumption, charge neutralization and particle dispersion, were applied to interfere with the effects of metal ion, polycyclic aromatic hydrocarbons (PAHs), reactive oxygen species (ROS), charge and size. It was found that aggregated size and PAHs could activate the NLRP3 inflammasome through lysosome rupture and potassium efflux, respectively. Metal ion, PAHs and surface ROS could also activate the NLRP3 inflammasome through mitochondrial ROS production. However, neutralization of PM2.5 with the negative surface charge could not relieve the activation of NLRP3 inflammasome. Furthermore, oropharyngeal aspiration of various modified PM2.5 were adopted to explore their effects on lung fibrosis, which showed the consistent results with those in cellular levels. Removal of metal ion, PAHs and ROS as well as reduction of size of PM2.5 could reduce collagen deposition in the lung tissue of mice, while the charge neutralization of PM2.5 increased this collagen deposition. This study provides great insights to clarify the property-activity relationship of PM2.5.

Tumor microcalcification-mediated relay drug delivery for photodynamic immunotherapy of breast cancer.

Spatiotemporal targeting of tumor-associated macrophages (TAMs) and tumor cells is emerging as a promising strategy for tumor therapy. Tumor microcalcifications that specifically bind to bisphosphonates are potentially used to design efficient relay drug delivery nanosystems to achieve spatiotemporal drug modulation. Here, we developed manganese dioxide (MnO2)-embedded and LyP-1 peptide-labeled liposomal nanoparticles (NPs) for photodynamic immunotherapy of breast cancer; zoledronic acid (Zol) was encapsulated in the hydrophilic cavity of liposomes, and a hydrophobic photosensitizer (IR780) was embedded in the phospholipid bilayer of liposomes. These Lipo Zol/IR NPs generated O2 bubbles through MnO2 in response to H2O2 in the tumor microenvironment, leading to the degradation of the liposomal membrane, which triggered the release of Zol and provided O2 for photodynamic therapy. The released Zol attached to microcalcifications and was selectively phagocytosed by TAMs, leading to the induction of death or repolarization of TAMs from the immunosuppressive M2 phenotype to the immunostimulatory M1 phenotype. The remaining liposomal fragments embedded with IR780 then preferentially targeted tumor cells through LyP-1 peptide and produced abundant reactive oxygen species (ROS) under near infrared (NIR) laser irradiation, resulting in the death of tumor cells and mild immune activation. All in vitro and in vivo studies demonstrated the effective photodynamic and immunoregulatory performance of Lipo Zol/IR NPs. STATEMENT OF SIGNIFICANCE: Spatiotemporal targeting of tumor-associated macrophages (TAMs) and tumor cells remains a challenge in tumor photodynamic immunotherapy for promoting synergy and reducing side effects. Here, we developed tumor microcalcification-mediated relay drug delivery nanoliposomes for breast cancer therapy. H2O2 in the tumor microenvironment (TME) triggers the breakage of nanoliposomes, thereby causing the separation of zoledronic acid (Zol) and the photosensitizer IR780 and allowing them to perform their respective functions. Microcalcifications enable Zol to target TAMs, resulting in immunomodulation. LyP-1 guides IR780 to target tumor cells for PDT with adequate O2 supply. These nanoliposomes enable precise spatiotemporal targeting of different types of cells in the TME and promote the synergy between immunotherapy and PDT while ensuring the effectiveness of both methods.

Neutrophil mediated postoperative photoimmunotherapy against melanoma skin cancer.

Surgery is the primary treatment option for most melanoma; however, high tumor recurrence rate after surgical resection becomes the main cause of death in cancer patients. The development of efficient drug delivery nanosystems to inhibit postoperative tumor recurrence becomes very necessary. In the present study, IR780 molecules and TRP-2 peptide were encapsulated in the hydrophobic shell and hydrophilic interior of TAT peptide functionalized liposomes to form TLipIT NPs, which were further internalized into neutrophils (NEs) to achieve TLipIT/NEs. After being intravenously injected into postoperative B16F10-bearing mice, TLipIT/NEs could actively migrate toward the inflamed residual tumor and release TLipIT through neutrophil extracellular traps (NETs). Under NIR laser irradiation, the TLipIT exhibited both photothermal and photodynamic effects to induce immunogenic cell death for maturation of DCs, and simultaneously, to release TRP-2 peptide as a melanoma associated antigen to further strengthen the maturation of DCs, both of which prompts the activation of T cells and induces potent immune responses. TLipIT/NEs hold great potential for the inhibition of postoperative tumor recurrence.

Biodegradable Copper-Based Nanoparticles Augmented Chemodynamic Therapy through Deep Penetration and Suppressing Antioxidant Activity in Tumors.

Chemodynamic therapy (CDT) efficacy has been limited by the poor penetration ability of large nanoparticles (NPs) and the antioxidant activity of tumors, especially high heme oxygenase (HO-1) and glutathione (GSH) levels. Herein, PEGylated CuMoOx -coated and zinc protoporphyrin IX (ZP)-loaded Cu (CCMZ) NPs are designed to afford rapid degradation ability and augmented CDT efficacy through inhibiting HO-1 activity and depleting GSH. The deep penetration of tumor can be achieved under the high levels of GSH, which triggers the degradation of CuMoOx shell. Meanwhile, GSH itself is depleted, which converts the reductive environment into constant oxidative environment, thus leading to the degradation of Cu core. Furthermore, the release of ZP from CCMZ NPs can inhibit HO-1 activity and provide a favorable microenvironment for CDT, and the release of Cu and Mo ions can convert hydrogen peroxide into hydroxyl radical to eliminate tumor cells more efficiently. In addition, CCMZ NPs also play an immune vaccine-like effect to recruit different immune cells for antitumor immunotherapy. In vitro and in vivo studies prove the augmented CDT property of CCMZ NPs, supplying a new strategy for improving CDT efficacy.

Biotransformation of soluble-insoluble lanthanum species and its induced NLRP3 inflammasome activation and chronic fibrosis.

Soluble lanthanum (La)(Ⅲ) species that have been extensively used as fertilizers in agriculture can potentially get into the human body through foods and environment. Most soluble La(Ⅲ) species can rapidly transform into insoluble La(Ⅲ) species under physiological conditions, however, their potential biological behavior and chronic toxicity are rarely investigated. In the present study, insoluble La(Ⅲ) species formed under physiological condition were identified as nanoscale or microscale particles, and their major components were found to experience biotransformation process upon contact with cells. Insoluble La(Ⅲ) species could adhere to extracellular membrane or be internalized into cells, capable of activating a nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome. The underlying mechanism could be ascribed to K+ efflux and lysosomal rupture because these insoluble La(Ⅲ) species locating at extracellular membrane could reduce the unsaturated fatty acids of cell membrane, leading to potassium (K+) efflux, and those internalized into cells could consume the phospholipids of lysosomal membrane, leading to lysosomal rupture. Mice daily drinking soluble La(Ⅲ) species to mimic drinking tea process for 90 days were found to present NLRP3 inflammasome activation in liver and kidney, as a result of chronic fibrosis, which is potentially correlated to insoluble La(Ⅲ) species formation.

Copper Phosphide Nanoparticles Used for Combined Photothermal and Photodynamic Tumor Therapy.

Copper-based nanomaterials are widely used in near-infrared (NIR) light-mediated deep tumor treatment because of their abundant photothermal and photodynamic properties. However, copper phosphide (Cu3P) nanoparticles (NPs) are rarely investigated. Herein, Cu3P NPs were prepared to strengthen their local surface plasmon resonance absorption in the NIR region, exhibiting promising photothermal and photodynamic properties. After surface modification by polyethylene glycol, the formed pCu3P NPs showed negligible influence on the viability of 4T1 cells, presenting remarkable biocompatibility. However, with 808 nm irradiation, pCu3P NPs could induce HSP70 and HO-1 protein expression and enhance intracellular reactive oxygen species levels, leading to dramatic cell death. In 4T1 tumor-bearing mice, an intravenous injection of biocompatible pCu3P NP could lead to remarkable aggregation in the tumor region and significantly inhibit tumor growth under 808 nm laser irradiation, presenting great potential for tumor therapy.

Immunomodulation of Tumor Microenvironment by Arginine-Loaded Iron Oxide Nanoparticles for Gaseous Immunotherapy.

Tumor-associated macrophages (TAMs) of M2 phenotype have mediated the immunosuppression in a tumor microenvironment, facilitating the escape of tumor cells from immunosurveillance. Reprograming the immunosuppressive M2 TAMs to immunostimulatory M1 phenotype can activate the antitumor immune responses for cancer immunotherapy. Herein, hollow iron oxide (Fe3O4) nanoparticles (NPs) were employed to reprogram M2 TAMs toward M1 TAMs, aiming to release proinflammatory cytokines and recruit T cells to kill tumor cells. After loaded with l-arginine (l-Arg) and sealed with poly(acrylic acid) (PAA), hollow Fe3O4 NPs were fabricated into LPFe3O4 NPs, which could release l-Arg based on pH-responsive PAA and produce nitric oxide (NO) with the help of nitric oxide synthase (iNOS) overexpressed by M1 TAMs, as a result of additional tumor elimination for gas therapy. In vitro and in vivo studies demonstrate that LPFe3O4 NPs could effectively reprogram M2 to M1 macrophages, activating T cells, releasing TNF-α, and producing high levels of NO, leading to synergistic tumor therapy.

Thylakoid Membranes with Unique Photosystems Used to Simultaneously Produce Self-Supplying Oxygen and Singlet Oxygen for Hypoxic Tumor Therapy.

Photodynamic therapy (PDT) efficacy has been dramatically limited by the insufficient oxygen (O2 ) level in hypoxic tumors. Although various PDT nanosystems have been designed to deliver or produce O2 in support of reactive oxygen species (ROS) formation, the feature of asynchronous O2 generation and ROS formation still results in the low PDT efficacy. Herein, thylakoid membranes (TM) of chloroplasts is decorated on upconversion nanoparticles (UCNPs) to form UCTM NPs, aiming at realizing spatiotemporally synchronous O2 self-supply and ROS production. Upon 980 nm laser irradiation, UC NPs can emit the red light to activate both photosystem-I and photosystem-II of TM, the Z-scheme electronic structure of which facilitates water to produce O2 and further to singlet oxygen (1 O2 ). UCTM NPs showed excellent biocompatibility, and can effectively remove the hypoxic tumor of mice upon 980 nm laser irradiation. This study develops a new PDT strategy for hypoxic tumor therapy based on photosynthesis.

A biomimetic nanoenzyme for starvation therapy enhanced photothermal and chemodynamic tumor therapy.

Photothermal therapy (PTT) and chemodynamic therapy (CDT) are promising therapeutic modalities with high specificity, however, a single therapeutic modality cannot maximize therapeutic efficacy. In the present study, glucose oxidase (GOx) was decorated on N-doped carbon (NC) nanoparticles (NPs) as a biomimetic nanoenzyme (NC@GOx NPs), which could promote starvation therapy enhanced PTT and CDT against tumors. GOx could decompose to cut off the supply of energy and nutrients, inducing starvation therapy, which further lowered adenosine triphosphate (ATP) levels, inducing downregulated heat shock proteins and creating a more suitable microenvironment for improving PTT efficacy. Meanwhile, the generated endogenous hydrogen peroxide (H2O2) could be converted into hydroxyl radicals to attack cancer cells. In fact, in vitro and in vivo experiments demonstrated that NC@GOx NPs could effectively kill cancer cells and eliminate tumors. This design provides a strategy for synergistic cancer therapy by using biomimetic nanoenzymes.

Improving the photothermal therapy efficacy and preventing the surface oxidation of bismuth nanoparticles through the formation of a bismuth@bismuth selenide heterostructure.

Bismuth (Bi) nanoparticles (NPs) are emerging as promising photothermal agents for computed tomography imaging-guided photothermal therapy. However, it is challenging to improve their photothermal conversion efficacy and prevent their oxidation. Herein, Bi@bismuth selenide (Bi2Se3) core@shell NPs were designed and fabricated for improving the photothermal performance due to the staggered energy levels between Bi and Bi2Se3. With near-infrared light irradiation, both the materials could be excited to generate hot carriers due to their extremely narrow bandgaps. The hot electrons would transfer to the conduction band of Bi2Se3 and the hot holes to the valence band of Bi, leading to the effective separation of hot carriers. Then, these hot electrons and holes would recombine nonradiatively at the interface of Bi and Bi2Se3 and produce more phonons, resulting in an enhanced photothermal conversion efficacy. Moreover, the presence of Bi2Se3 on the surface of Bi NPs could prevent Bi from surface oxidation due to the higher stability of Bi2Se3. In fact, Bi@Bi2Se3 NPs showed excellent biocompatibility and photothermal therapeutic efficacy against cancer cells.

Safety-by-Design of Metal Oxide Nanoparticles Based on the Regulation of their Energy Edges.

The safety of metal oxide (MOx) nanoparticles (NPs) has been highly concerned because of their wide application and potential toxicological injury. The safe-by-design strategy is usually developed to make safer MOx NPs based on regulation of their physicochemical properties. In the present study, manganese oxide (Mn3 O4 ) NPs, as a representative of insoluble toxic MOx NPs, are doped with a series of transition metal to regulate their conduction band energy (Ec ) out of biological redox potential range (BRPR) or Fermi energy (Ef ) far away from valence band energy (Ev ), aiming at completely eliminating the toxicity or significantly reducing the toxicity. It is found that all these M-doping cannot move Ec of Mn3 O4 NPs out of the BRPR but zinc (Zn)-, copper (Cu)-, and chromium (Cr)-doping do move Ef far away from Ev , where Zn-doping results in the largest |Ef - Ev | value. Various abiotic, in vitro and in vivo assessments reveal that Zn-, Cu-, and Cr-doped Mn3 O4 NPs can generate lower amount of •OH and trigger weaker injury than Mn3 O4 NPs, where Zn-doped Mn3 O4 NPs show the lowest toxicity. Regulating Ef far away from Ev becomes a feasible safe-by-design approach to achieve safe MOx NPs.

Spatiotemporally Synchronous Oxygen Self-Supply and Reactive Oxygen Species Production on Z-Scheme Heterostructures for Hypoxic Tumor Therapy.

Photodynamic therapy (PDT) efficacy has been severely limited by oxygen (O2 ) deficiency in tumors and the electron-hole separation inefficiency in photosensitizers, especially the long-range diffusion of O2 toward photosensitizers during the PDT process. Herein, novel bismuth sulfide (Bi2 S3 )@bismuth (Bi) Z-scheme heterostructured nanorods (NRs) are designed to realize the spatiotemporally synchronous O2 self-supply and production of reactive oxygen species for hypoxic tumor therapy. Both narrow-bandgap Bi2 S3 and Bi components can be excited by a near-infrared laser to generate abundant electrons and holes. The Z-scheme heterostructure endows Bi2 S3 @Bi NRs with an efficient electron-hole separation ability and potent redox potentials, where the hole on the valence band of Bi2 S3 can react with water to supply O2 for the electron on the conduction band of Bi to produce reactive oxygen species. The Bi2 S3 @Bi NRs overcome the major obstacles of conventional photosensitizers during the PDT process and exhibit a promising phototherapeutic effect, supplying a new strategy for hypoxic tumor elimination.

Nitric Oxide Stimulated Programmable Drug Release of Nanosystem for Multidrug Resistance Cancer Therapy.

Nitric oxide (NO) molecular messenger can reverse the multidrug resistance (MDR) effect of cancer cells through reducing P-glycoprotein (P-gp) expression, beneficial for creating a favorable microenvironment for the treatment of doxorubicin (Dox)-resistant cancer cells. Development of sophisticated nanosystems to programmably release NO and Dox becomes an efficient strategy to overcome the MDR obstacles and achieve promising therapeutic effects in Dox-resistant cancer. Herein, a NO stimulated nanosystem was designed to engineer a significant time gap between NO and Dox release, promoting MDR cancer therapy. A o-phenylenediamine-containing lipid that can hydrolyze in response to NO was embedded in the phospholipid bilayer structure of liposome to form NO-responsive liposome, which could further encapsulate l-arginine (l-Arg)/Dox-loaded gold@copper sulfide yolk-shell nanoparticls (ADAu@CuS YSNPs) to form ADLAu@CuS YSNPs. Under 808 nm laser irradiation, the unique resonant energy transfer (RET) process and reactive oxygen species (ROS) generation in the confined space of ADLAu@CuS YSNPs could effectively convert l-Arg into NO, regionally destabilizing the phospholipid bilayer structure, as a result of NO release. However, at this early stage Dox could not be released from YSNPs due to the molecular scaffold limit. As the NO release progressed, the NO-responsive liposome layer was deteriorated more severely, allowing Dox to escape. This NO and Dox sequential release of ADLAu@CuS YSNPs could significantly inhibit P-gp expression and enhance Dox accumulation in Dox-resistant MCF-7/ADR cells, leading to promising in vitro and in vivo therapeutic effects and presenting their great potential for MDR cancer therapy.

Hierarchical Acceleration of Wound Healing through Intelligent Nanosystem to Promote Multiple Stages.

Wound healing is a dynamic, interactive, and complex process, including multiple stages. Although various nanomaterials are applied to accelerate the wound healing process through exhibiting antibacterial activity or promoting cell proliferation, only a single stage is promoted during the process, lowering healing efficacy. It is necessary to develop programmable nanosystems for promoting multiple wound healing stages in sequence. Herein, arginine-loaded and detachable ceria-graphene nanocomposites (ACG NCs) were designed to achieve this purpose. Ceria NPs and graphene were linked by base-cleavable N-hydroxysuccinimide ester. At inflammation stage, ACG NCs could effectively generate reactive oxygen species (ROS) and kill bacteria under white light irradiation due to their efficient electron-hole separation between ceria NPs and graphene. At proliferation stage, ceria NPs could be detached from ACG NCs and taken up by cells to scarify intracellular ROS and promote cell proliferation, while the separated graphene could act as a scaffold to promote fibroblast migration to wound site. A series of in vitro and in vivo assessments demonstrated that ACG NCs could effectively accelerate wound healing process.

Time-staggered delivery of erlotinib and doxorubicin by gold nanocages with two smart polymers for reprogrammable release and synergistic with photothermal therapy.

Photochemotherapy is currently an effective anticancer therapy. Recently, it has been reported that cancer cells pretreated with epidermal growth factor receptor (EGFR) inhibitor erlotinib (Erl) can significantly synergize its apoptosis against the DNA damaging agent doxorubicin (Dox). As a result, we designed two gold nanocages (Au NCs) microcontainers covered with different smart polymer shell-PAA (pH responsive) and p (NIPAM-co-AM) (temperature responsive) containing Erl and Dox respectively. The acidic tumor microenvironment and NIR light irradiation can selectively activate the release of Erl and Dox. Time staggered release of Erl and Dox and photothermal therapy enhance the apoptotic signaling pathways, resulting in improved tumor cell killing in both MCF-7 (low EGFR expression) and A431 (very high EGFR expression) tumor cells, but more efficient in the latter. The photochemotherapy strategy controls the order and duration of drug exposure precisely in spatial and temporal, and significantly improves the therapeutic efficacy against high EGFR expressed tumors.

Hollow, Rough, and Nitric Oxide-Releasing Cerium Oxide Nanoparticles for Promoting Multiple Stages of Wound Healing.

Wound healing is a complex and sequential biological process that involves multiple stages. Although various nanomaterials are applied to accelerate the wound healing process, only a single stage is promoted during the process, lacking hierarchical stimulation. Herein, hollow CeO2 nanoparticles (NPs) with rough surface and l-arginine inside (Ah CeO2 NPs) are developed as a compact and programmable nanosystem for sequentially promoting the hemostasis, inflammation, and proliferation stages. The rough surface of Ah CeO2 NPs works as a nanobridge to rapidly closure the wounds, promoting the hemostasis stage. The hollow structure of Ah CeO2 NPs enables the multireflection of light inside particles, significantly enhancing the light harvest efficiency and electron-hole pair abundance. Simultaneously, the porous shell of Ah CeO2 NPs facilitates the electron-hole separation and reactive oxygen species production, preventing wound infection and promotion wound healing during the inflammation stage. The enzyme mimicking property of Ah CeO2 NPs can alleviate the oxidative injury in the wound, and the released l-arginine can be converted into nitric oxide (NO) under the catalysis of inducible NO synthase, both of which promote the proliferation stage. A series of in vitro and in vitro biological assessments corroborate the effectiveness of Ah CeO2 NPs in the wound healing process.

Anisotropic Plasmonic Metal Heterostructures as Theranostic Nanosystems for Near Infrared Light-Activated Fluorescence Amplification and Phototherapy.

The development of sophisticated theranostic systems for simultaneous near infrared (NIR) fluorescence imaging and phototherapy is of particular interest. Herein, anisotropic plasmonic metal heterostructures, Pt end-deposited Au nanorods (PEA NRs), are developed to efficiently produce hot electrons under 808 nm laser irradiation, exhibiting the strong electric density. These hot electrons can release the heat through electron-phonon relaxation and form reactive oxygen species through chemical transformation, as a result of potent photothermal and photodynamic performance. Simultaneously, the confined electromagnetic field of PEA NRs can transfer energy to adjacent polyethylene glycol (PEG)-linked NIR fluorophores (CF) based on their energy overlap mechanism, leading to remarkable NIR fluorescence amplification in CF-PEA NRs. Various PEG linkers (1, 3.4, 5.0, and 10 kD) are employed to regulate the distance between CF and PEA NRs of CF-PEA NRs, and the maximum fluorescence intensity is achieved in CF5k-PEA NRs. After further attachment with i-motif DNA/Nrf2 siRNA chimera to simultaneously suppress both cellular antioxidant defense and hyperthermia resistance effects, the final biocompatible CF5k-bPEA@siRNA NRs present promising NIR fluorescence imaging ability and 808 nm laser-activated photothermal and photodynamic therapeutic effect in MCF7 cells and tumor-bearing mice, holding great potential for cancer therapy.