An "Outer Piezoelectric and Inner Epigenetic" Logic-Gated PANoptosis for Osteosarcoma Sono-Immunotherapy and Bone Regeneration.

The precise manipulation of PANoptosis, a newly defined cell death pathway encompassing pyroptosis, apoptosis, and necroptosis, is highly desired to achieve safer cancer immunotherapy with tumor-specific inflammatory responses and minimal side effects. Nonetheless, this objective remains a formidable challenge. Herein, an "AND" logic-gated strategy for accurately localized PANoptosis activation, utilizing composite 3D-printed bioactive glasses scaffolds integrated with epigenetic regulator-loaded porous piezoelectric SrTiO nanoparticles is proposed.

A dual-targeting therapeutic nanobubble for imaging-guided atherosclerosis treatment.

Atherosclerosis is a cardiovascular disease that seriously endangers human health. Low shear stress (LSS) is recognized as a vital factor in causing chronic inflammatory and further inducing the occurrence and development of atherosclerosis. Targeting imaging and treatment are of substantial significance for the diagnosis and therapy of atherosclerosis.

Engineering Self-Assembled Nanomedicines Composed of Clinically Approved Medicines for Enhanced Tumor Nanotherapy.

The traditional nanocarriers are typically constructed to deliver anticancer agents for improving drug bioavailability and enhancing chemotherapeutic efficacy, but this strategy suffers from the critical issue of nanocarrier biosafety that hinders further clinical translation. In this work, a unique nanomedicine (PTX@ICG) has been rationally constructed by combining two clinically approved agents, i.e.

Nanosonosensitizers-engineered injectable thermogel for augmented chemo-sonodynamic therapy of melanoma and infected wound healing.

Easy recurrence and bacteria infected-wound healing after surgery excision pose severe challenges to clinical melanoma therapy. Herein, an injectable CuO nanodots-engineered thermosensitive chitosan hydrogel (CuO-BSO@Gel) for enhanced melanoma chemo-sonodynamic therapy and improved infected wound healing was rationally constructed by facilely integrating the CuO nanodots and L-Buthionine-(S, R)-sulfoximine (BSO) with thermoresponsive hydrogel. Favored by the Fenton catalytic activity of Cu, the CuO nanodots can achieve enhanced chemodynamic therapy (CDT) by self-supplying HO under acidic tumor microenvironment.

Engineering ROS-scavenging Prussian blue nanozymes for efficient atherosclerosis nanotherapy.

Atherosclerosis (AS), characterized by a chronic inflammatory disease, is a top cause of morbidity and disability worldwide. During the pathogenesis of AS, the leading process of inflammation highly involves a secondary event of oxidative stress, but limited antioxidants are currently available clinically due to their nonspecific effects, poor biosafety, and rapid elimination and urinary excretion as well as short retention time within plaque lesions. In this work, Prussian blue nanozymes with a strong reactive oxygen species (ROS)-scavenging ability were rationally engineered for efficient AS nanotherapy.

Ultrasound-enhanced cascade chemodynamic tumor nanotherapy with lactic acid-enabled hydrogen peroxide self-production.

Chemodynamic therapy (CDT) is an effective therapeutic modality for cancer treatment with the action of a catalytic Fenton-like chemoreactive process. To furnish sufficient hydrogen peroxide (HO) for CDT, catalysts similar to superoxide dismutase are designed to be in cooperation with nanoplatforms. In this work, we rationally integrate lactate oxidase (LOD) with ultrasmall superparamagnetic iron oxide nanoparticles (USPION) to achieve high efficiency of the cascade Fenton reaction for efficient tumor therapy.

Engineering Fe/Mn-doped zinc oxide nanosonosensitizers for ultrasound-activated and multiple ferroptosis-augmented nanodynamic tumor suppression.

As an effective tumor-therapeutic modality, ultrasound-triggered sonodynamic therapy (SDT) has been extensively explored to induce cancer cell death by activating sonosensitizers to generate reactive oxygen species (ROS). However, the traditional inorganic semiconductor-based sonosensitizers still suffer from inefficient ROS production because of the low separation efficiency of electrons and holes (e/h) and their fast recombination. Herein, the iron (Fe) and manganese (Mn) co-doped zinc oxide nanosonosensitizers have been rationally designed and engineered for augmenting the SDT efficiency against tumor by inducing both multiple ferroptosis and apoptosis of tumor cells.

Engineering 2D Silicene-Based Mesoporous Nanomedicine for In Vivo Near-Infrared-Triggered Analgesia.

The utilization of local anesthetics for postoperative analgesia represents an effective approach, but generally suffers from short half-lives and brachychronic local neurotoxicity. A desirable anesthetic with controllable and sustainable drug-releasing performance for adequate analgesia effect is highly required. In this work, the core/shell-structured two-dimenional (2D) silicene nanosheets coated with mesoporous silica layer (abbreviated as Silicene@MSNs) have been rationally constructed as localized drug-delivery system in sciatic nerve block to achieve on-demand release of loaded ropivacaine (RP) in mesoporous silica layer for local analgesia.

Oxygen-evolving photosynthetic cyanobacteria for 2D bismuthene radiosensitizer-enhanced cancer radiotherapy.

The local hypoxic tumor environment substantially hampers the therapeutic efficiency of radiotherapy, which typically requires the large X-ray doses for tumor treatment but induces the serious side effects. Herein, a biomimetic radiosensitized platform based on a natural oxygen-evolving photosynthetic cyanobacteria combined with two-dimensional (2D) bismuthene with high atomic-number (Z) components, is designed and engineered to effectively modulate the radiotherapy-resistant hypoxic tumor environment and achieve sufficient radiation energy deposition into tumor. Upon the exogenous sequential irradiation of 660 nm laser and X-ray beam, continuous photosynthetic oxygen evolution by the cyanobacteria and considerable generation of reactive oxygen species by the 2D bismuthene radiosensitizer substantially augmented the therapeutic efficacy of radiotherapy and suppressed the tumor growth, as demonstrated on both LLC-lung tumor xenograft-bearing C57/B6 mice model and 4T1-breast tumor xenograft-bearing Balb/c mice model, further demonstrating the photosynthetic hypoxia-alleviation capability and radiosensitization performance of the engineered biomimetic radiosensitized platform.

Redox chemistry-enabled stepwise surface dual nanoparticle engineering of 2D MXenes for tumor-sensitive and MRI-guided photonic breast-cancer hyperthermia in the NIR-II biowindow.

With the fast advent of two-dimensional (2D) MXenes, several therapeutic paradigms based on 2D MXenes flourish, but a generic strategy for MXene functionalization to achieve theranostic functionalities and desirable performance is still lacking. In this work, we report a facile and efficient stepwise surface-functionalization strategy to achieve distinct tumor microenvironment (TME)-responsive and magnetic resonance (MR) imaging-guided photothermal breast-cancer hyperthermia in the second near-infrared (NIR-II) biowindow. This approach is based on the stepwise growth of superparamagnetic FeO and paramagnetic MnO nanocomponents onto the large surface of ultrathin 2D niobium carbide (NbC) MXene nanosheets (FeO/MnO-NbC) by making full use of the redox status/chemistry of the 2D MXene surface.

Multifunctional Composite Nanosystems for Precise/Enhanced Sonodynamic Oxidative Tumor Treatment.

Ultrasound-activated therapies have been regarded as the efficient strategy for tumor treatment, among which sonosensitizer-enabled sonodynamic oxidative tumor therapy features intrinsic advantages as compared to other exogenous trigger-activated dynamic therapies. Nanomedicine-based nanosonosensitizer design has been extensively explored for improving the therapeutic efficacy of sonodynamic therapy (SDT) of tumor. This review focuses on solving two specific issues, i.

Co-delivery of nanoparticle and molecular drug by hollow mesoporous organosilica for tumor-activated and photothermal-augmented chemotherapy of breast cancer.

Background: In comparison with traditional therapeutics, it is highly preferable to develop a combinatorial therapeutic modality for nanomedicine and photothermal hyperthermia to achieve safe, efficient, and localized delivery of chemotherapeutic drugs into tumor tissues and exert tumor-activated nanotherapy. Biocompatible organic-inorganic hybrid hollow mesoporous organosilica nanoparticles (HMONs) have shown high performance in molecular imaging and drug delivery as compared to other inorganic nanosystems. Disulfiram (DSF), an alcohol-abuse drug, can act as a chemotherapeutic agent according to its recently reported effectiveness for cancer chemotherapy, whose activity strongly depends on copper ions.

Ultrathin 2D Inorganic Ancient Pigment Decorated 3D-Printing Scaffold Enables Photonic Hyperthermia of Osteosarcoma in NIR-II Biowindow and Concurrently Augments Bone Regeneration.

Osteosarcoma (OS) is the primary malignant bone tumor. Despite therapeutic strategies including surgery, chemotherapy, and radiotherapy have been introduced into the war of fighting OS, the 5-year survival rate for patients still remains unchangeable for decades. Besides, the critical bone defects after surgery, drug-resistance and side effects also attenuate the therapeutic effects and predict poor prognosis.

Mesoporous silica nanoparticles inflame tumors to overcome anti-PD-1 resistance through TLR4-NFκB axis.

Background: The clinical benefits of antiprogrammed cell death protein 1 (PD-1) therapy are compromised by resistance in immunologically cold tumors. Convergence of immunotherapy and bioengineering is potential to overcome the resistance. Mesoporous silica nanoparticles (MSNs) are considered the most promising inorganic biological nanomaterials for clinical transformation, however, the fundamental influence of MSNs on immunotherapy is unclear.

Autophagy blockade synergistically enhances nanosonosensitizer-enabled sonodynamic cancer nanotherapeutics.

Ultrasound-triggered sonodynamic therapy (SDT) represents an emerging therapeutic modality for cancer treatment based on its specific feature of noninvasiveness, high tissue-penetrating depth and desirable therapeutic efficacy, but the SDT-induced pro-survival cancer-cell autophagy would significantly lower the SDT efficacy for cancer treatment. Here we propose an "all-in-one" combined tumor-therapeutic strategy by integrating nanosonosensitizers-augmented noninvasive SDT with autophagy inhibition based on the rationally constructed nanoliposomes that co-encapsulates clinically approved sonosensitizers protoporphyrin IX (PpIX) and early-phase autophagy-blocking agent 3-methyladenine (3-MA). It has been systematically demonstrated that nanosonosensitizers-augmented SDT induced cytoprotective pro-survival autophagy through activation of MAPK signaling pathway and inhibition of AMPK signaling pathway, and this could be efficaciously inhibited by 3-MA in early-phase autophagy, which significantly decreased the cell resistance to intracellular oxidative stress and complied a remarkable synergistic effect on SDT medicated cancer-cell apoptosis both in vitro at cellular level and in vivo on tumor-bearing animal model.

Emerging Nanomedicine-Enabled/Enhanced Nanodynamic Therapies beyond Traditional Photodynamics.

The rapid knowledge growth of nanomedicine and nanobiotechnology enables and promotes the emergence of distinctive disease-specific therapeutic modalities, among which nanomedicine-enabled/augmented nanodynamic therapy (NDT), as triggered by either exogenous or endogenous activators on nanosensitizers, can generate reactive radicals for accomplishing efficient disease nanotherapies with mitigated side effects and endowed disease specificity. As one of the most representative modalities of NDT, traditional light-activated photodynamics suffers from the critical and unsurmountable issues of the low tissue-penetration depth of light and the phototoxicity of the photosensitizers. To overcome these obstacles, versatile nanomedicine-enabled/augmented NDTs have been explored for satisfying varied biomedical applications, which strongly depend on the physicochemical properties of the involved nanomedicines and nanosensitizers.

Chemoreactive Nanotherapeutics by Metal Peroxide Based Nanomedicine.

The advances of nanobiotechnology and nanomedicine enable the triggering of in situ chemical reactions in disease microenvironment for achieving disease-specific nanotherapeutics with both intriguing therapeutic efficacy and mitigated side effects. Metal peroxide based nanoparticles, as one of the important but generally ignored categories of metal-involved nanosystems, can function as the solid precursors to produce oxygen (O) and hydrogen peroxide (HO) through simple chemical reactions, both of which are the important chemical species for enhancing the therapeutic outcome of versatile modalities, accompanied with the unique bioactivity of metal ion based components. This progress report summarizes and discusses the most representative paradigms of metal peroxides in chemoreactive nanomedicine, including copper peroxide (CuO), calcium peroxide (CaO), magnesium peroxide (MgO), zinc peroxide (ZnO), barium peroxide (BaO), and titanium peroxide (TiO) nanosystems.

Self-assembled organic nanomedicine enables ultrastable photo-to-heat converting theranostics in the second near-infrared biowindow.

Development of organic theranostic agents that are active in the second near-infrared (NIR-II, 1000-1700 nm) biowindow is of vital significance for treating deep-seated tumors. However, studies on organic NIR-II absorbing agents for photo-to-heat energy-converting theranostics are still rare simply because of tedious synthetic routes to construct extended π systems in the NIR-II region. Herein, we design a convenient strategy to engineer highly stable organic NIR-II absorbing theranostic nanoparticles (Nano-BFF) for effective phototheranostic applications via co-assembling first NIR (NIR-I, 650-1000 nm) absorbing boron difluoride formazanate (BFF) dye with a biocompatible polymer, endowing the Nano-BFF with remarkable theranostic performance in the NIR-II region.

The Coppery Age: Copper (Cu)-Involved Nanotheranostics.

As an essential trace element in the human body, transitional metal copper (Cu) ions are the bioactive components within the body featuring dedicated biological effects such as promoting angiogenesis and influencing lipid/glucose metabolism. The recent substantial advances of nanotechnology and nanomedicine promote the emerging of distinctive Cu-involved biomaterial nanoplatforms with intriguing theranostic performances in biomedicine, which are originated from the biological effects of Cu species and the physiochemical attributes of Cu-composed nanoparticles. Based on the very-recent significant progresses of Cu-involved nanotheranostics, this work highlights and discusses the principles, progresses, and prospects on the elaborate design and rational construction of Cu-composed functional nanoplatforms for a diverse array of biomedical applications, including photonic nanomedicine, catalytic nanotherapeutics, antibacteria, accelerated tissue regeneration, and bioimaging.

Ultrasmall AgTe Quantum Dots with Rapid Clearance for Amplified Computed Tomography Imaging and Augmented Photonic Tumor Hyperthermia.

With the fast development of nanomedicine, the imaging-guided and photo-induced cancer monotherapies can efficiently eliminate tumor lesions, which are strongly dependent on the construction of versatile theranostic nanoplatforms. Among diverse photo-converting nanoplatforms, silver chalcogenide nanoparticles feature high biocompatibility, narrow band gaps, and tunable optical properties, yet AgTe-based nanosystems are still at a proof-of-concept stage, and the exploration of AgTe-based nanosystems suitable for photonic tumor hyperthermia is challenging. Herein, we report on the construction of versatile ultrasmall AgTe quantum dots (QDs) via a facile biomineralization strategy.

Energy-converting biomaterials for cancer therapy: Category, efficiency, and biosafety.

Energy-converting biomaterials (ECBs)-mediated cancer-therapeutic modalities have been extensively explored, which have achieved remarkable benefits to overwhelm the obstacles of traditional cancer-treatment modalities. Energy-driven cancer-therapeutic modalities feature their distinctive merits, including noninvasiveness, low mammalian toxicity, adequate therapeutic outcome, and optimistical synergistic therapeutics. In this advanced review, the prevailing mainstream ECBs can be divided into two sections: Reactive oxygen species (ROS)-associated energy-converting biomaterials (ROS-ECBs) and hyperthermia-related energy-converting biomaterials (H-ECBs).

Energy Conversion-Based Nanotherapy for Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA) is characterized by synovial hyperplasia and cartilage/bone destruction, which results in a high disability rate on human health and a huge burden on social economy. At present, traditional therapies based on drug therapy still cannot cure RA, in accompany with the potential serious side effects. Based on the development of nanobiotechnology and nanomedicine, energy conversion-based nanotherapy has demonstrated distinctive potential and performance in RA treatment.

Bioinspired Copper Single-Atom Catalysts for Tumor Parallel Catalytic Therapy.

The oxidation of intracellular biomolecules by reactive oxygen species (ROS) forms the basis for ROS-based tumor therapy. However, the current therapeutic modalities cannot catalyze H O and O concurrently for ROS generation, thereby leading to unsatisfactory therapeutic efficacy. Herein, it is reported a bioinspired hollow N-doped carbon sphere doped with a single-atom copper species (Cu-HNCS) that can directly catalyze the decomposition of both oxygen and hydrogen peroxide to ROS, namely superoxide ion (O • ) and the hydroxyl radical (•OH), respectively, in an acidic tumor microenvironment for the oxidation of intracellular biomolecules without external energy input, thus resulting in an enhanced tumor growth inhibitory effect.