Microenvironment-Responsive Targeted Nanomedicine for a Collaborative Integration of Tumor Theranostics and Bone Defect Repair.

Despite advancements in breast cancer treatment, bone metastases remain a significant concern for patients with advanced breast cancer. Current theranostics strategies face challenges in integrating tumor theranostics and bone formation. Herein, we developed an activatable targeted nanomedicine AuMnCO@BSA-N3 (AMCBN) to enable a novel collaborative integration of second near-infrared (NIR-II) fluorescence imaging guided precise theranostics for breast cancer bone metastases and osteogenic microenvironment remolding. This strategy employed a chemical coordination between noble metal complex and metal carbonyl (MnCO). The surface modification of azide groups for enhanced tumor affinity through passive and active targeting. The initiated respondent behavior of AMCBN by tumor microenvironment (H2O2/acidity) accelerate the degradation of coordinated MnCO, resulting in a rapid release of multifunctional agents for efficient chemodynamic therapy (CDT)/gas synergistic therapy. Meanwhile, the exceptional bone-binding properties enable the efficient and controlled release of Mn2+ ions and CO in the bone microenvironment, thereby facilitating the expression of osteogenesis-related proteins and establishing a novel synchronous theranostics process for tumor-bone repair. This article is protected by copyright. All rights reserved.

A Multifunctional Nanoreactor-Induced Dual Inhibition of HSP70 Strategy for Enhancing Mild Photothermal/Chemodynamic Synergistic Tumor Therapy.

Mild photothermal therapy (PTT) is a spatiotemporally controllable method that utilizes the photothermal effect at relatively low temperatures (40-45 °C) to especially eliminate tumor tissues with negligible side effects on the surrounding normal tissues. However, the overexpression of heat shock protein 70 (HSP70) and limited effect of single treatment drastically impede the therapeutic efficacy. Herein, the constructed multifunctional core-shell structured Ag-Cu@SiO2-PDA/GOx nanoreactors (APG NRs) that provide a dual inhibition of HSP70 strategy for the second near-infrared photoacoustic (NIR-II PA) imaging-guided combined mild PTT/chemodynamic therapy (CDT). The Ag-Cu cores can convert endogenous H2O2 to hydroxyl radical (•OH), which can induce lipid peroxidation (LPO) and further degrade HSP70. The polydopamine (PDA)/glucose oxidase (GOx) shells are utilized as the NIR-II photothermal agent to generate low temperature, and the GOx can reduce the energy supplies and inhibit energy-dependent HSP70 expression. Furthermore, both the generation of •OH and GOx-mediated energy shortage can reduce HSP70 expression to sensitize mild PTT under 1064 nm laser, and in turn, GOx and laser self-amplify the catalytic reactions of APG NRs for more production of •OH. The multifunctional nanoreactors will provide more potential possibilities for the clinical employment of mild PTT and the advancement of tumor combination therapies.

NIR-II Absorption/Emission Dual-Function-Based 2D Targeted Nanotheranostics for Tunable Hydrogenothermal Therapy.

Photothermal therapy (PTT) is a promising approach for treating tumors that offers multiple advantages. Nevertheless, its practical use in clinical settings faces several limitations, such as suboptimal delivery efficiency, uneven heat distribution, and challenges in predicting optimal treatment duration. In addition, the localized hyperthermia generated by the PTT method to induce cell apoptosis can result in the production of excessive reactive oxygen species (ROS) and the release of inflammatory cytokines, which can pose a threat to the healthy tissues surrounding the tumor. To address the above challenges, we designed an integrated H2 delivery nanoplatform for multimodal imaging H2 thermal therapy. The combination of the second near-infrared window (NIR-II) fluorescence imaging (FL) agent (CQ4T) and the photothermal and photoacoustic (PA) properties of Ti3C2 (TC) enables real-time monitoring of the tumor area and guides photothermal treatment. Simultaneously, due to the acid-responsive H2 release characteristics of the nanoplatform, H2 can be utilized for synergistic photothermal therapy to eradicate tumor cells effectively. Significantly, acting as an antioxidant and anti-inflammatory agent, Ti3C2-BSA-CQ4T-H2 (TCBCH) protects peritumoral normal cells from damage. The proposed technique utilizing H2 gas for combination therapies and multimodal imaging integration exhibits prospects for effective and secure treatment of tumors in future clinical applications. This article is protected by copyright. All rights reserved.

A novel NIR-II FL/ PA imaging-guided synergistic photothermal-immune therapy: Biomineralizing nanosystems integrated with anti-tumor and bone repair.

Advanced stages of breast cancer are frequently complicated by bone metastases, which cause significant cancer-related bone destruction and mortality. However, the early precise theranostics of bone metastasis remains a formidable challenge in clinical practice. Herein,a novel all-in-one nanotheranostic system (ABI NYs) combining NIR-II FL/PA dual-modal imaging with photothermal-immunity therapeutic functionalities in one component was designed to precisely localize bone metastasis microscopic lesions and achieve complete tumor ablation at an early stage. The surface modification of the nanosystem with ibandronate (IBN) facilitates both passive and active targeting, significantly improving the detection rate of bone metastasis and suppressing the bone resorption. Superior photothermal performance produces sufficient heat to kill tumor cells while stimulating the upregulation of heat shock proteins 70 (HSP70), which triggers the immunogenic cell death (ICD) effect and the anti-tumor immune response. These all-in-one nanosystems precisely demonstrated early lesion localization in bone metastases and total tumor ablation with a single integration via "one-component, multi-functions" technique. To sum up, ABI NYs, as novel biomineralizing nanosystems integrated with anti-tumor and bone repair, present a synergistic therapy strategy, providing insight into the theranostics of bone metastases and clinical research.

Dual regulation of osteosarcoma hypoxia microenvironment by a bioinspired oxygen nanogenerator for precise single-laser synergistic photodynamic/photothermal/induced antitumor immunity therapy.

The hypoxic tumor microenvironment (TME) of osteosarcoma (OS) is the Achilles' heel of oxygen-dependent photodynamic therapy (PDT), and tremendous challenges are confronted to reverse the hypoxia. Herein, we proposed a "reducing expenditure of O2 and broadening sources" dual-strategy and constructed ultrasmall IrO2@BSA-ATO nanogenerators (NGs) for decreasing the O2-consumption and elevating the O2-supply simultaneously. As O2 NGs, the intrinsic catalase (CAT) activity could precisely decompose the overexpressed H2O2 to produce O2 in situ, enabling exogenous O2 infusion. Moreover, the cell respiration inhibitor atovaquone (ATO) would be at the tumor sites, effectively inhibiting cell respiration and elevating oxygen content for endogenous O2 conservation. As a result, IrO2@BSA-ATO NGs systematically increase tumor oxygenation in dual ways and significantly enhance the antitumor efficacy of PDT. Moreover, the extraordinary photothermal conversion efficiency allows the implementation of precise photothermal therapy (PTT) under photoacoustic guidance. Upon a single laser irradiation, this synergistic PDT, PTT, and the following immunosuppression regulation performance of IrO2@BSA-ATO NGs achieved a superior tumor cooperative eradicating capability both in vitro and in vivo. Taken together, this study proposes an innovative dual-strategy to address the serious hypoxia problem, and this microenvironment-regulable IrO2@BSA-ATO NGs as a multifunctional theranostics platform shows great potential for OS therapy.

Endogenous Melanin and Hydrogen-Based Specific Activated Theranostics Nanoagents: A Novel Multi-Treatment Paradigm for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by excessive proliferation of rheumatoid arthritis synovial fibroblasts (RASFs) and accumulation of inflammatory cytokines. Exploring the suppression of RASFs and modulation of the RA microenvironment is considered a comprehensive strategy for RA. In this work, specifically activated nanoagents (MAHI NGs) based on the hypoxic and weakly acidic RA microenvironment are developed to achieve a second near-infrared fluorescence (NIR-II FL)/photoacoustic (PA) dual-model imaging-guided multi-treatment. Due to optimal size, the MAHI NGs passively accumulate in the diseased joint region and undergo rapid responsive degradation, precisely releasing functionalized components: endogenous melanin-nanoparticles (MNPs), hydrogen gas (H2), and indocyanine green (ICG). The released MNPs play a crucial role in ablating RASFs within the RA microenvironment through photothermal therapy (PTT) guided by accurate PA imaging. However, the regional hyperthermia generated by PTT may exacerbate reactive oxygen species (ROS) production and inflammatory response following cell lysis. Remarkably, under the acidic microenvironment, the controlled release of H2 exhibits precise synergistic antioxidant and anti-inflammatory effects with MNPs. Moreover, the ICG, the second near-infrared dye currently approved for clinical use, possesses excellent NIR-II FL imaging properties that facilitate the diagnosis of deep tissue diseases and provide the right time-point for PTT.

A Novel Activatable Nanoradiosensitizer for Second Near-Infrared Fluorescence Imaging-Guided Safe-Dose Synergetic Chemo-Radiotherapy of Rheumatoid Arthritis.

The precise theranostics of rheumatoid arthritis (RA) remains a formidable challenge in clinical practice. Exploring novel applications of contemporary therapeutic approaches like chemo-radiotherapy is promising as a highly effective strategy for RA. Herein, a novel activatable nanoradiosensitizer-40 (denoted as IRnR-40) is developed, based on encapsulating the clinically approved drugs cisplatin (DDP) and indocyanine green (ICG) within a gelatin shell to achieve second near-infrared fluorescence (NIR-II FL) imaging-guided safe-dose synergetic chemo-radiotherapy. The high concentration of matrix metalloproteinase-9 (MMP-9) in the RA microenvironment plays a pivotal role in triggering the responsive degradation of IRnR-40, leading to the rapid release of functional molecules DDP and ICG. The released ICG serves the dual purpose of illuminating the inflamed joints to facilitate accurate target volume delineation for guiding radiotherapy, as well as acting as a real-time reporter for quantifying the release of DDP to monitor efficacy. Meanwhile, the released DDP achieves highly effective synergistic chemotherapy and radiosensitization for RA via the dual reactive oxygen species (ROS)-mediated mitochondrial apoptotic pathway. To sum up, this activatable nanoradiosensitizer IRnR-40 is believed to be the first attempt to achieve efficient NIR-II FL imaging-guided safe-dose chemo-radiotherapy for RA, which provides a new paradigm for precise theranostics of refractory benign diseases.

Homology-Activated Ultrasensitive Nanomedicines for Precise NIR-II FL/MRI Imaging-Guided "Knock-On" Dynamic Therapy in Rheumatoid Arthritis.

Stimuli-responsive nanomedicines represent a pivotal technology for in situ on-demand drug release and offer multiple advantages over conventional drug delivery systems to combat rheumatoid arthritis(RA). However, the lack of sensitivity to a single-stimuli source or the inability to synchronize multi-stimuli responses can easily lead to challenges in achieving precise-theranostics of RA. Herein, a homology-activated ultrasensitive nanomedicines MnO2-CQ4T-GOx(MCG NMs) is designed for NIR-II fluorescence(NIR-II FL)/magnetic resonance imaging(MRI)-guided effective "knock-on" dynamic anti-RA therapy. Building upon the characteristics of the RA-microenvironment, the MCG innovatively construct a MnO2-Mn2+ system, which can normalized activation sites. The ultrasensitive-responsive degradation is achieved using the multi-stimuli processes in the RA-microenvironment, triggering release of functional small molecules. The produced Mn2+ can exert Fenton-like activity to generate •OH from H2O2, thus providing the effective chemodynamic therapy(CDT). Moreover, the up-regulation of H2O2 by GOx-catalysis not only sensitizes the MnO2-Mn2+ system but also achieves self-enhancing CDT efficacy. The NIR-II FL quenching of CQ4T-BSA in the aggregated state occurs in MCG NMs, which can be rapidly and precisely "turn-on" via the MnO2-Mn2+ system. Meanwhile, the integration of activated Mn2+-based MRI imaging has successfully developed an activatable dual-modal imaging. Feedback imaging-guided precise photodynamic therapy of CQ4T-BSA can achieve efficient "knock-on" dynamic therapy for RA.

A Single NIR-II Laser-Triggered Self-Enhancing Photo/Enzyme-coupled Three-in-One Nanosystems for Breast Cancer Phototheranostics.

Multifunctional phototheranostics, employing precise and non-invasive techniques, is widely developed to enhance theranostic efficiency of breast cancer (BC), reduce side-effects, and improve quality of life. Integrating all phototheranostic modalities into a single photosensitizer for highly effective BC treatment is particularly challenging due to the potential inefficiency and time consumption associated with repeated switching of multiple-wavelength lasers. Herein, a novel single NIR-II laser-triggered three-in-one nanosystem(PdCu NY) is rationally designed, which enables dual-modal (NIR-II FL/NIR-II PA) imaging-guided self-enhancing photothermal-photodynamic therapy (PTT-PDT) in NIR-II window. The PdCu NY based on optimal Pd/Cu molar-ratio(1:11) can be easily fabricated and large-scale production for simultaneous PTT-PDT against BC under a single 1064nm laser irradiation. Significantly, the PdCu NY acted as a promising photocatalyst for decomposition of H2O into O2 upon the same laser irradiation. In addition, the inherent catalase (CAT)-like activity of PdCu NYs enables photo-enzyme dual-catalytic O2 supply to effectively alleviate hypoxia, achieving self-enhanced PDT efficiency. These PTT-PDT self-enhanced nanosystems demonstrate precise lesion localization and complete tumor ablation using a single 1064nm laser source by "one-laser, multi-functions" strategy. More importantly, this study not only reports a three-in-one PdCu-based phototheranostic agent, but also sheds light on the exploration of versatile biosafety nanosystems for clinical applications.

Biomimetic Theranostic Agents with Superior NIR-II Photoacoustic and Magnetic Resonance Imaging Performance for Targeted Photothermal Therapy of Prostate Cancer.

The accurate diagnosis and treatment of prostate cancer at an early stage is crucial to reduce mortality rates. However, the limited availability of theranostic agents with active tumor-targeting abilities hinders imaging sensitivity and therapeutic efficiency. To address this challenge, we have developed biomimetic cell membrane-modified Fe2O3 nanoclusters implanted in polypyrrole (CM-LFPP), achieving photoacoustic/magnetic resonance dual-modal imaging-guided photothermal therapy of prostate cancer. The CM-LFPP exhibits strong absorption in the second near-infrared window (NIR-II, 1000-1700 nm), showing high photothermal conversion efficiency of up to 78.7% under 1064 nm laser irradiation, excellent photoacoustic imaging capabilities, and good magnetic resonance imaging ability with a T2 relaxivity of up to 48.7 s-1 mM-1. Furthermore, the lipid encapsulation and biomimetic cell membrane modification enable CM-LFPP to actively target tumors, leading to a high signal-to-background ratio of ~30.2 for NIR-II photoacoustic imaging. Moreover, the biocompatible CM-LFPP enables low-dose (0.6 W cm-2) photothermal therapy of tumors under 1064 nm laser irradiation. This technology offers a promising theranostic agent with remarkable photothermal conversion efficiency in the NIR-II window, providing highly sensitive photoacoustic/magnetic resonance imaging-guided prostate cancer therapy.

A novel bidirectional perfusion-like administered system for NIR-II fluorescence imaging precision diagnosis of bladder cancer.

Intravesical instillation has been considered an efficient route for detecting bladder cancer. However, only a small fraction of administered dose permeates into tumor tissues, and insufficient retention time limits their application. In this work, a novel intravesical bidirectional perfusion-like administered mode was developed to improve diagnostic accuracy of bladder tumor imaging. Specifically, the ultrasmall AuPd-P-FA Nanoprobe exhibit excellent NIR-II FL imaging performance due to electronic structure perturbation. Benefiting from the size advantage for kidney metabolism and FA targeting specificity, AuPd-P-FA could effectively administration to bladder tumor. When AuPd-P-FA reached maximum enrichment at 1 h post-injection, the localized and mild thermal energy produced upon laser irradiation activated a phase transition. This thermo-sensitive characteristic could prolong the retention time in bladder and the fluorescence signal could be clearly observed at 6 h post-injection with high accuracy. This novel intravesical bidirectional perfusion-like administered mode is expected to achieve a non-invasive diagnosis of early bladder cancer.

Multifunctional AuPd-cluster nanotheranostic agents with a cascade self-regulating redox tumor-microenvironment for dual-photodynamic synergized enzyme catalytic therapy.

Photodynamic therapy (PDT) has emerged as a promising strategy with higher selectivity and spatiotemporal control than conventional therapies. However, deep hypoxia in tumours has hampered the clinical use of PDT. In this study, a novel multifunctional cluster nanotheranostic agent (AuPd-BSA CN) was fabricated to generate a high amount of reactive oxygen species, regardless of oxygen dependence under 660 nm laser irradiation. The structure and properties of the AuPd-BSA CN were characterised using various technologies. The synthesised AuPd-BSA CN with high biocompatibility served as a superior photodynamic agent, showing prominent antitumour properties under laser irradiation. Additionally, the glucose oxidase-like activity of the AuPd-BSA CN synergistically enhanced the therapeutic performance. Notably, the intrinsic characteristics of the AuPd-BSA CN include dual-modal second near-infrared window fluorescence/photoacoustic imaging capabilities for monitoring and tracking the in vivo tumour therapeutic process. This work provides innovative insights into the AuPd-BSA CN as an "all-in-one" nanoplatform for cancer therapy.

Cyclic enhancement of hypoxic microenvironment via an intelligent nanoamplifier for activated NIR-II fluorescence/photoacoustic imaging-guided precise synergistic therapy.

Tumor microenvironment (TME)-activated theranostics is a promising strategy to effectively identify small lesions, improve antitumor efficacy, and reduce the risk of undesired side effects. Hypoxia, as a common characteristic of TME, can serve as a preferred site for stimulus-dependent activation; however, tumor-hypoxia levels in various developmental stages exhibit different characteristics, severely limiting the response sensitivity. Herein, a circulating self-reinforcing hypoxic nanoamplifier (CGH NAs) is developed that utilizes a dual-chain reaction process (internal regulation, internal regulation) to achieve precise activation of NIR-II FL/photoacoustic (PA) imaging-guided synergistic therapy. Inspired by the positive correlation of nitroreductase (NTR) with hypoxia, the CGH NAs encapsulate CQ4T and GOx into NTR-sensitive hyaluronic acid-nitroimidazole (HA-NI) shell via a self-assembly approach, enabling aggregation-caused NIR-II FL quenching and tumor-accurate delivery. When CGH NAs efficiently accumulated in the tumor region, the intensive local NTR reduced hydrophobic -NO2 to hydrophilic -NH2, which lead to disassembly of CGH NAs. The released GOx could consume O2 (internal regulation) and glucose to cut off the energy supply, inducing tumor-starvation therapy; generate gluconic acid and H2O2 (oxidative stress). Meanwhile, the released CQ4T promoted rapid recovery of NIR-II FL signals for imaging-guided PDT, which could simultaneously deplete intratumoral O2 (external stimulation). Remarkably, the strengthened tumor-hypoxia levels in turn accelerated the NTR-responsive degradation of the CGH NAs, thereby achieving high-efficiency theranostic.

Dual H2 O2 -Amplified Nanofactory for Simultaneous Self-Enhanced NIR-II Fluorescence Activation Imaging and Synergistic Tumor Therapy.

Activatable fluorescence imaging in the second near-infrared window (NIR-II FL, 1000-1700 nm) is of great significance for accurate tumor diagnosis and targeting therapy. However, the clinical translation of most stimulus-activated nanoprobes is severely restricted by insufficient tumor response and out-of-synchronization theranostic process. Herein, an intelligent nanofactory AUC-GOx/Cel that possesses the "external supply, internal promotion" dual H2 O2 -amplification strategy for homologous activated tumor theranostic is designed. This nanofactory is constructed via a two-step biomineralization method using Au-doped Ag2 S as a carrier for glucose oxidase (GOx) and celastrol, followed by the growing of CuS to "turn off" the NIR-II FL signal. In the overexpressed H2 O2 tumor-microenvironment, the CuS featuring a responsive-degradability behavior can effectively release Cu ions, resulting in the "ON" state of NIR-II FL and Fenton-like activity. The exposed GOx can realize the intratumoral H2 O2 supply (external supply) via the effective conversion of glucose, and mediating tumor-starvation therapy; the interaction of celastrol and mitochondria can offer a substantial increase in the endogenous H2 O2 level (internal promotion), thereby significantly promoting the chemodynamic therapy (CDT) efficacy. Meanwhile, the dual H2 O2 -enhancement performance will in turn accelerate the degradation of AUC-GOx/Cel, and achieve a positive feedback mechanism for self-reinforcing CDT.

A "Dual-Source, Dual-Activation" Strategy for an NIR-II Window Theranostic Nanosystem Enabling Optimal Photothermal-Ion Combination Therapy.

The activatable imaging technique in the second near-infrared window (NIR-II) utilizes the stimulation of cancer-associated biomarkers for specific imaging to guide precise NIR-II photothermal therapy. However, most activatable nanoprobes with single-source stimulation are insufficient in providing comprehensive information regarding the tumor, severely restricting the therapeutic optimization, especially in NIR-II photothermal therapy (PTT)-based combination therapy. Herein, a "dual-source, dual-activation" strategy-based multifunctional nanosystem, PPAC, is reported as a promising tool for activatable NIR-II fluorescence (FL)/ratiometric photoacoustic (PA) imaging-guided "localization-timing" photothermal-ion therapy (PTIT). A fibroblast activation protein (FAP)-responsive peptide to modify the surface of Pd nanosheets with excellent NIR-II absorption ability can efficiently cross-link BSA-CQ4T to realize NIR-II FL quenching, followed by the loading of Ag to construct the PPAC. Triggered by the specific cleavage with FAP on the perivascular cancer-associated fibroblasts (first source), the PPAC can correspondingly release BSA-CQ4T for rapid fluorescence recovery. The nanosystems are subsequently taken up by tumor cells, where the overexpressed H2 O2 (second source) promotes the oxidation of Ag shell to Ag+ , and further leads the real-time ratiometric PA signals (Ag-PA660/Pd-PA1050) that can monitor the Ag+ ions-related production efficiency and therapeutic performance. Intelligent integration of dual-modality imaging information can comprehensively provide the right time-point and site-specificity for selective NIR-II PTT.

All-in-One Zeolite-Carbon-Based Nanotheranostics with Adjustable NIR-II Window Photoacoustic/Fluorescence Imaging Performance for Precise NIR-II Photothermal-Synergized Catalytic Antitumor Therapy.

In the second near-infrared (NIR-II) biowindow, multimodal optical imaging-guided precise antitumor therapy is a novel strategy for high-efficiency tumor theranostics, however, the all-in-one dual NIR-II photoacoustic (NIR-II PA) and NIR-II fluorescence (NIR-II FL) nanoprobes have been rarely reported mainly due to the short of a simple and universal design approach. Herein, a NIR-II PA/NIR-II FL imaging-adjustable nanozyme (HSC-2) is designed and developed to guide precise photothermal-catalytic synergistic therapy. Based on the ionic liquids adsorption capacity, the electronic structure of zeolite nano-Beta (three dimensional 12-ring pore system and large surface area) can be turned from the indirect band gap to direct band gap via doping carbon in the framework, resulting in outstanding NIR-II FL emission characteristics. As the silicon etching reaction proceeds, HSC-2 shows superior dual-modal NIR-II PA/NIR-II FL imaging performance facilitated by the optimal silicon-to-carbon ratio, simultaneously ensuring efficient tumor photothermal therapy (PTT) in the NIR-II window. Impressively, the peroxidase-mimic activity of HSC-2 in the tumor microenvironment could be further remarkably enhanced by its photothermal effect, leading to excellent synergistic PTT/catalytic therapy. Moreover, the HSC-2 exhibits dual-enzyme activity, and its catalase-like property could effectively eliminate excessive ROS for protection of the normal cells.

Fibroblast Activation Protein-α as a Target in the Bench-to-Bedside Diagnosis and Treatment of Tumors: A Narrative Review.

Fibroblast activation protein-α (FAP) is a type II integral serine protease that is specifically expressed by activated fibroblasts. Cancer-associated fibroblasts (CAFs) in the tumor stroma have an abundant and stable expression of FAP, which plays an important role in promoting tumor growth, invasion, metastasis, and immunosuppression. For example, in females with a high incidence of breast cancer, CAFs account for 50-70% of the cells in the tumor's microenvironment. CAF overexpression of FAP promotes tumor development and metastasis by influencing extracellular matrix remodeling, intracellular signaling, angiogenesis, epithelial-to-mesenchymal transition, and immunosuppression. This review discusses the basic biological characteristics of FAP and its applications in the diagnosis and treatment of various cancers. We review the emerging basic and clinical research data regarding the use of nanomaterials that target FAP.

Biodegradable Silica-Based Nanotheranostics for Precise MRI/NIR-II Fluorescence Imaging and Self-Reinforcing Antitumor Therapy.

Multi-modality cancer diagnosis techniques based on the second near-infrared window fluorescence (NIR-II FL, 1000-1700 nm) imaging have become the focus of research attention. For such multimodality probes, how to take advantage of the tumor microenvironments (TME) characteristics to better image diseases and combine efficient therapeutics to achieve theranostics is still a big challenge. Herein, a novel TME-activated nanosystem (FMSN-MnO2 -BCQ) employing degradable silica-based nanoplatform is designed, adjusting the ratio of intratumoral hydrogen peroxide (H2 O2 )/glutathione (GSH) for magnetic resonance imaging (MRI)/NIR-II FL imaging and self-reinforcing chemodynamic therapy (CDT). Innovative bovine serum albumin (BSA)-modified fusiform-like mesoporous silica nanoparticles (FMSN) is fabricated as a carrier for NIR-II small molecule (CQ4T) and MRI reporter MnO2 . Remarkably, the BSA modification helped to achieve the dual-functions of high biocompatibility and enhance NIR-II fluorescence. The FMSN-MnO2 -BCQ with FMSN framework featuring a stepwise degradability in tumor interior released MnO2 and BCQ nanoparticles. Through the specific degradation of MnO2 by the TME, the produced Mn2+ ions are effectively exerted Fenton-like activity to generate hydroxyl radical (•OH) from endogenous H2 O2 to eradicate tumor cells. More importantly, the GSH depletion due to the synergistic effect of tetrasulfide bond and MnO2 in turn induced the oxidative cytotoxicity for self-reinforcing CDT.

Hollow carbon-based nanosystem for photoacoustic imaging-guided hydrogenothermal therapy in the second near-infrared window.

Compared with the near-infrared-I spectral window (NIR-I, 650-950 nm), a newly developed imaging and treatment window with a 1000-1700 nm range (defined as the NIR-II bio-window) has attracted much attention owing to its higher spatiotemporal resolution, increased tissue penetration depth and therapeutic efficacy. Herein, we designed a nanotheranostic platform (HC-AB NPs) via loading ammonia borane (AB) into hollow carbon nanoparticles (HCs) for NIR-II photoacoustic (PA) imaging-guided NIR-II hydrogenothermal therapy. Importantly, by exploiting the characteristics of beta zeolite as a hard template and a template-carbonization-corrosion process, the prepared HCs have excellent NIR-II absorption performance and AB loading capacity. With the high biocompatibility of HC-AB NPs, an efficient synergistic anti-tumor strategy has been achieved via high intratumoural accumulation and acid-stimulated H2 release as well as PA-guided precise NIR-II photothermal therapy. The HC-AB NPs as a promising nanotheranostic platform opens a new avenue for high-efficacy NIR-II hydrogenothermal therapy.

Biodegradable Multifunctional Nanotheranostic Based on Ag2S-Doped Hollow BSA-SiO2 for Enhancing ROS-Feedback Synergistic Antitumor Therapy.

Stimuli-responsive silica nanoparticles are an attractive therapeutic agent for effective tumor ablation, but the responsiveness of silica nanoagents is limited by intrastimulation level and silica framework structure. Herein, a biodegradable hollow SiO2-based nanosystem (Ag2S-GOx@BHS NYs) is developed by a novel one-step dual-template (bovine serum albumin (BSA) and cetyltrimethylammonium bromide (CTAB)) synthetic strategy for image-guided therapy. The Ag2S-GOx@BHS NYs can be specifically activated in the tumor microenvironment via a self-feedback mechanism to achieve reactive oxygen species (ROS)-induced multistep therapy. In response to the inherent acidity and H2O2 at the tumor sites, Ag2S-GOx@BHS would accelerate the structural degradation while releasing glucose oxidase (GOx), which could efficiently deplete intratumoral glucose to copious amounts of gluconic acid and H2O2. More importantly, the sufficient H2O2 not only acts as a reactant to generate Ag+ from Ag2S for metal-ion therapy and improves the oxidative stress but also combines with gluconic acid results in the self-accelerating degradation process. Moreover, the released Ag2S nanoparticles can help the Ag2S-GOx@BHS NYs realize the second near-infrared window fluorescence (NIR-II FL) and photoacoustic (PA) imaging-guided precise photothermal therapy (PTT). Taken together, the development of a self-feedback nanosystem may open up a new dimension for a highly effective multistep tumor therapy.