The integration of conventional 1H MRI with heteronuclear 19F MRI enables the concurrent acquisition of complementary anatomical and molecular imaging information using a single instrument. Here, we report a T1-T2 dual-modal MRI platform based on gadolinium-albumin (Gd-BSA) nanostructures synthesized through a biomimetic mineralization strategy. To endow multifunctionality, perfluoropentaphenyl-15-crown-5 ether (PFCE) and the photosensitizer IR780 were coencapsulated, yielding the theranostic probe IR780@PFCE@Gd-BSA (IPGB). IPGB exhibited strong 19F MRI signals and T1-T2 contrast enhancement on clinical and preclinical MRI systems (1.5, 3.0, and 9.4 T), confirming its potential for 1H/19F multimodal imaging. Beyond imaging, IPGB exhibited superior photodynamic therapy (PDT) efficacy compared with free IR780. In vivo, IPGB achieved passive tumor accumulation with prolonged retention, enabled high-resolution multimodal MRI, and significantly suppressed breast tumor growth after PDT. Collectively, these results highlight IPGB as a viable multifunctional nanoplatform for cancer diagnosis, real-time multimodal imaging, and image-guided therapy.

Magnetic resonance imaging (MRI) techniques are essential for the diagnosis of hepatocellular carcinoma (HCC) and the development of precise treatment strategies. Multifunctional diagnostic agents integrating MRI capabilities have attracted considerable interest in precision oncology. In this study, a biomimetic nanoparticle (HAMM NPs) is engineered through the synthesis of Mn 2+ -doped mesoporous polydopamine (Mn-MPDA) as a drug carrier, followed by loading the hydrophilic sonosensitizer artesunate (ART) and coating with Hepa1-6 cell membranes. The resulting Hepa1-6@ART@Mn-MPDA nanoparticles (HAMM NPs) exhibit enhanced tumor accumulation owing to the homologous targeting capability conferred by the Hepa1-6 cell membrane. Under the acidic conditions of the tumor microenvironment, HAMM NPs undergo pH-triggered release of Mn 2+ and ART. HAMM NPs exhibit excellent T 1 /T 2 dual-modality MRI capability enabling precise liver cancer imaging and MRI-guided sonodynamic therapy (SDT). Upon ultrasound activation, ART generates cytotoxic reactive oxygen species in an oxygen-independent manner, which synergizes with Mn 2+ -mediated chemodynamic therapy via Fenton-like reactions. In both subcutaneous and orthotopic HCC models, HAMM NPs effectively inhibit tumor growth. This strategy overcomes the limitations of conventional SDT in hypoxic tumors, offering a promising approach for imaging-guided combination therapy against deep-seated tumors.

The integration of conventional 1H MRI with heteronuclear 19F MRI enables the concurrent acquisition of complementary anatomical and molecular imaging information using a single instrument. Here, we report a T1-T2 dual-modal MRI platform based on gadolinium-albumin (Gd-BSA) nanostructures synthesized through a biomimetic mineralization strategy. To endow multifunctionality, perfluoropentaphenyl-15-crown-5 ether (PFCE) and the photosensitizer IR780 were coencapsulated, yielding the theranostic probe IR780@PFCE@Gd-BSA (IPGB). IPGB exhibited strong 19F MRI signals and T1-T2 contrast enhancement on clinical and preclinical MRI systems (1.5, 3.0, and 9.4 T), confirming its potential for 1H/19F multimodal imaging. Beyond imaging, IPGB exhibited superior photodynamic therapy (PDT) efficacy compared with free IR780. In vivo, IPGB achieved passive tumor accumulation with prolonged retention, enabled high-resolution multimodal MRI, and significantly suppressed breast tumor growth after PDT. Collectively, these results highlight IPGB as a viable multifunctional nanoplatform for cancer diagnosis, real-time multimodal imaging, and image-guided therapy.

Conventional metal-based contrast agents for magnetic resonance imaging (MRI) present concerns regarding potential chronic toxicity with prolonged use and inherently lack therapeutic functionality. Integrating the antioxidant 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), which possesses intrinsic paramagnetic properties, into nanocarriers presents a promising solution to these challenges. Herein, we synthesized a TEMPO-grafted block copolymer that self-assembles into nanoparticles encapsulating olsalazine (OS) to create TBATM@OS. In vitro experiments demonstrated the potential of TBATM@OS for MRI-guided drug delivery and effective clearance of reactive oxygen species (ROS). Consequently, TBATM@OS enables clear MRI detection of intestinal inflammation and effectively reduces inflammation, unlike the clinical agent Magnevist, which was unable to visualize inflamed sites. Mechanistic studies revealed that TBATM@OS modulates TNF signaling pathways, restores intestinal barrier homeostasis, and balances gut microbiota. This bifunctional nanoagent provides a therapeutic strategy for imaging and sustained alleviation of colon inflammation.

Systemic administration of the anti-rheumatic drug methotrexate (MTX) for a long period of time may lead to therapeutic tolerance, various adverse effects, and potential harm to the immune system. Therapeutic nano-delivery carriers constructed based on biologically active phenols provide a promising approach to enhance the therapeutic effect of anti-rheumatic drugs. Caffeic acid, a natural compound with anti-inflammatory properties, holds significant potential in the treatment of diverse inflammatory conditions. In this paper, we first constructed a nano-delivery platform for MTX using caffeic acid-based polyphenol polymer Ph-CaA-OH (PCOH), and investigated the treatment of rheumatoid arthritis (RA) at low drug administration doses (2.5 mg/kg). PCOH nanoparticles (NPs) could inhibit lipopolysaccharides-stimulated macrophage inducible nitric oxide synthase (iNOS) expression and pro-inflammatory differentiation in vitro. In vivo imaging revealed the rapid accumulation and sustained presence of PCOH NPs at inflamed joints in collagen induced-arthritis (CIA) mice. Therapeutic evaluation of CIA mice demonstrated that MTX@PCOH NPs were superior to free MTX in reducing the progression of RA and decreasing the expression of multiple pro-inflammatory cytokines without significant toxic effects. By enhancing drug aggregation at inflammatory joints and capitalizing on the synergistic effects of active carriers, MTX@PCOH NPs effectively minimized the required drug dosage and mitigated toxic side effects in RA treatment. The application of PCOH NPs to RA treatment provides a new strategy for the development of safer and more effective anti-RA nanomedicines.

Bridging tumor diagnosis and therapy remains a major challenge, largely due to the clinical separation of imaging and treatment, compounded by the low relaxivity of conventional MRI contrast agents. To address these limitations, we developed a copper-manganese hybrid nanogel (CMNG) via the in situ incorporation of Mn2+ ions and CuS nanoparticles within a cross-linked polymeric network. This multifunctional design enables T1-weighted MRI-guided photothermal-chemodynamic therapy. The nanogel matrix significantly enhances the relaxivity of paramagnetic Mn2+ ions (r1 = 10.81 mM-1 s-1), surpassing that of clinically approved Gd-based agents. Under 808 nm laser irradiation, CMNG exhibits efficient photothermal conversion (η = 23.29%), which synergistically enhances Cu+/Mn2+-mediated Fenton-like reactions, resulting in elevated hydroxyl radical (˙OH) production for effective tumor ablation and inhibition of tumor progression. This work presents a rational materials design strategy for integrated theranostic platforms. By combining MRI-guided tracking with potent therapeutic efficacy, the CMNG system offers a promising paradigm for precision cancer theranostics.

Acute kidney injury (AKI) is a critical condition marked by a rapid decline in renal function, primarily driven by oxidative stress, mitochondrial dysfunction, and inflammation. Despite extensive research, effective therapeutic strategies addressing the complex pathophysiology of AKI remain limited. In this study, we prepared a tannic acid‑cerium nanoenzyme (TA-Ce) and explored its potential for treating AKI. TA-Ce, synthesized via a one-pot method, demonstrated strong reactive oxygen species (ROS) scavenging, therapeutic efficacy, and biocompatibility in vitro and in vivo. TA-Ce, approximately 25.6 nm in size, was obtained by optimizing the molar ratios of TA to Ce and pH conditions, resulting in effective accumulation in the injured kidney. In addition, TA-Ce exhibited broad-spectrum antioxidant ability, capable of scavenging various ROS and alleviating oxidative stress. Notably, TA-Ce outperformed the conventional anti-inflammatory drug N-acetylcysteine (NAC) in both rhabdomyolysis-induced AKI (RM-AKI) and cisplatin-induced AKI (CP-AKI) mouse models. Mechanistic studies in RM-AKI revealed that TA-Ce disrupted the vicious cycle of oxidative stress, mitochondrial damage, endoplasmic reticulum stress, apoptosis, and inflammation. The nanoenzyme restored mitochondrial autophagic flux by inhibiting the P62-LC3 signaling pathway and alleviated endoplasmic reticulum stress by suppressing the IRE1-XBP1s pathway. Consequently, this prevented the downstream activation of the Bcl-2-Bax-Cyt-c-Cleaved Casp-3 apoptotic pathway and the NF-κB inflammatory pathway, ultimately ameliorating RM-AKI. This study lays a strong foundation for the development of metal-polyphenol nanomaterials as a therapeutic strategy for clinical AKI.

Combining chemotherapy with carbon monoxide (CO) gas therapy holds promise in treating diverse malignant tumors, particularly attributed to CO's capacity to enhance chemotherapeutic cytotoxicity on cancer cells. However, practical implementation is hindered by the limited bioavailability of chemotherapy agents and metal carbonyls, as well as the risk of premature drug leakage leading to side effects. To address these challenges, a highly stable DF@LCs drug delivery platform with siloxane framework surface was developed for controlled co-delivery of chemotherapy and CO gas therapy agents. The resulting DF@LCs encapsulated both the chemotherapeutic agent doxorubicin (DOX) and CO prodrug Triiron dodecarbonyl (Fe3(CO)12). Upon reaching the tumor site, the Fe3(CO)12 could react with endogenous hydrogen peroxide (H2O2) in the tumor microenvironment, producing CO gas. This CO generation process was significantly accelerated by the application of ultrasound (US), which triggered the formation of transient pores in the bilayer membrane of the DF@LCs, allowing for the rapid and targeted release of DOX. Concurrently, the generated CO selectively damaged the mitochondria of tumor cells, thereby inducing apoptosis and contributing to overall tumor cell death. In vitro studies demonstrated the remarkable efficacy of DF@LCs when combined with US. Intravenous administration of DF@LCs led to efficient accumulation within the tumor, and the subsequent application of US elicited a synergistic effect, dramatically suppressing tumor growth, with tumor volumes in treated mice being reduced by approximately 90 % compared to untreated controls. To further enhance the therapeutic potential, the DF@LCs+US system was integrated with programmed death-ligand 1 (PD-L1) antibody therapy in a 4 T1 mouse model. This triple therapy not only augmented the direct cytotoxic effects of DOX and CO on tumor cells but also significantly modulated the tumor immune microenvironment. Specifically, it was observed that treatment led to a marked increase in the infiltration of CD4+ helper T cells and CD8+ cytotoxic T cells within the tumor, while concurrently reducing the presence of immunosuppressive regulatory T cells (Tregs). This immune reprogramming effectively shifted the balance towards a more robust antitumor immune response, contributing to enhanced tumor inhibition and a significant reduction in lung metastases.

Correction for 'Dual-targeting hybrid nanoparticles for the delivery of SN38 to Her2 and CD44 overexpressed human gastric cancer' by Zhe Yang et al., Nanoscale, 2016, 8, 11543-11558, https://doi.org/10.1039/C6NR01749E.

The construction of highly efficient theranostic materials is critical for accurate lesion diagnosis and treatment. Among various diagnostic modalities, magnetic resonance imaging (MRI) is gaining attention due to its safety and precision. This study presents a novel theranostic agent, TPZ@TSF, that integrates 19F MRI for diagnostic imaging with photodynamic therapy (PDT) and hypoxia-activated tirapazamine (TPZ) as therapeutic modalities. TPZ@TSF is created through host-guest supramolecular interactions between β-cyclodextrin and adamantane, facilitating the development of complex functional materials. Investigations reveal that TPZ@TSF exhibits substantial intensity amplification in 19F NMR/MRI when exposed to glutathione (GSH), both in vitro and in vivo, achieving a long T2 relaxation time of 1267 ms, ensuring its excellent diagnostic profile. In vivo19F MRI results indicate that TPZ@TSF accumulates in tumors within 8 hours after intravenous administration in mice, providing an ideal timeframe for starting PDT and chemotherapy. Furthermore, therapeutic evaluations suggest that TPZ@TSF enhances chemotherapy efficacy against tumor growth by reducing hypoxia levels through the consumption of oxygen molecules during PDT. This innovative work is anticipated to significantly advance 19F MRI-guided therapy and improve the development of advanced theranostic agents.

19F magnetic resonance imaging (19F MRI) is an emerging non-invasive imaging modality with a high signal-to-noise ratio (SNR) and negligible background interference from biological tissues. However, the hydrophobic nature of fluorine atoms limits both 19F signal intensity and in vivo applicability. Therefore, developing fluorinated MRI contrast agents that combine high fluorine content with good hydrophilicity is essential for advancing in vivo 19F MRI. In this study, a fluorine-containing nanogel (FNG) is synthesized via emulsion polymerization and de-protection using trifluoroethyl methacrylate (TFMA) and tert-butyl acrylate (t-BA). The FNG is then loaded with the near-infrared photosensitizer IR780 to obtain a multifunctional imaging probe (IFNG) capable of dual-modal 19F MR and fluorescence (FL) imaging-guided photodynamic therapy (PDT). The resulting IFNG exhibited a T2 relaxation time of 46.32 ms, confirming its excellent MRI performance in vitro. In the tumor microenvironment, IFNG undergoes glutathione (GSH)-responsive decrosslinking, which exposes the encapsulated IR780. This process enhances fluorescence signal and promotes reactive oxygen species (ROS) generation under near-infrared light, thereby triggering effective PDT. Overall, these findings demonstrate IFNG as a promising nanoplatform that integrates dual-modal 19F MR/FL imaging with GSH-activated photodynamic therapy, offering great potential for precise tumor localization and image-guided cancer treatment.

Fluorine-19 magnetic resonance imaging (19F MRI) offers distinct advantages, including background-free signal detection, quantitative analysis, and deep tissue penetration. However, its application is currently limited by challenges associated with existing 19F MRI contrast agents, such as short transverse relaxation times (T2), limited imaging sensitivity, and suboptimal biocompatibility. To overcome these limitations, a glutathione (GSH)-responsive triblock copolymer (PB7), featuring self-immolative characteristics, has been developed. In aqueous solution, PB7 can spontaneously self-assemble into a 19F MRI contrast agent (SPTF), which exhibits a long T2 relaxation time and GSH-responsive T2 prolongation. Notably, during the self-assembly process of PB7, the photosensitizer Chlorin e6 (Ce6) can be encapsulated inside of the hydrophobic domain of SPTF, resulting in the formation of a multifunctional nanotheranostic agent (Ce6@SPTF). Ce6@SPTF is able to undergo structural disintegration in response to elevated GSH levels at the tumor site, leading to the dissociation of fluorinated segments and a marked amplification of the 19F MRI signal. Concurrently, the controlled release of Ce6 generates high levels of reactive oxygen species (ROS) under laser irradiation, enabling effective in vivo ablation of breast tumors. This study presents a promising strategy to effectively combine 19F MRI with therapeutic interventions.

Ultrahigh-field magnetic resonance imaging (UHF MRI) offers distinct advantages in medical imaging when compared to traditional low-field MRI technologies. However, due to inherent physical limitations, conventional contrast agents (such as gadolinium chelates and iron oxide nanoparticles) exhibit poor relaxation performance under strong magnetic field conditions. In contrast, the lanthanide element dysprosium (Dy) has demonstrated significant potential in constructing UHF MRI contrast agents, owing to its high magnetic moment and extremely short electron relaxation time. In this study, we developed a glutathione (GSH)-responsive self-immolative polymer theranostic platform (CA4@SIPD) chelated with Dy (III) for UHF MRI-guided hepatocellular carcinoma therapy. The polymer contains disulfide bonds that undergo GSH-triggered self-immolative cascade degradation in tumor sites, allowing controlled release of combretastatin A4 (CA4), a potent vascular-disrupting agent, to inhibit tumor growth. Simultaneously, the chelated Dy (III) endows the system with high-performance T2-weighted UHF MRI capabilities. This nanoplatform integrates UHF MRI compatibility with microenvironment-responsive drug delivery, providing real-time tumor-targeted visualization and synchronous therapeutic monitoring.

Colorectal cancer is a common cancer worldwide. Traditional chemotherapeutic drugs often face limitations such as poor aqueous solubility and high systemic toxicity, which can lead to adverse side effects and limited therapeutic efficacy. In this study, a library of one kind of biodegradable and biocompatible polymer, leucine based-poly(ester amide)s (Leu-PEAs) was developed and utilized as drug carrier. The structure of Leu-PEAs can be tuned to alter their physicochemical properties, enhancing drug loading capacity and delivery efficiency. Leu-PEAs can self-assemble into nanoparticles by nanoprecipitation and load paclitaxel (PTX) with the diameter of ∼108 nm and PTX loading capacity of ∼8.5%. PTX-loaded Leu-PEAs nanoparticles (PTX@Leu-PEAs) demonstrated significant inhibition of CT26 cell growth in vitro. In vivo, these nanoparticles exhibited prolonged tumor accumulation and antitumor effects, with no observed toxicity to normal organs. Furthermore, blank Leu-PEAs nanoparticles also showed antitumor effects in vitro and in vivo, which may be attributed to the activation of the mammalian target of rapamycin (mTOR) pathway by leucine. Consequently, this biocompatible Leu-PEAs nano-drug delivery system shows potential as a promising strategy for colorectal cancer treatment, warranting further investigation.

Treatment of highly aggressive triple-negative breast cancer (TNBC) in the clinic is challenging. Here, a liposome nanodrug (LP@PFH@HMME) integrating imaging agents and therapeutic agents for bimodal imaging-guided sonodynamic therapy (SDT) is developed, which boosted immunogenicity to enable potent immunotherapy via immune checkpoint blockade (ICB) in TNBC. In the acidic tumor microenvironment (TME), LP@PFH@HMME undergoes "nano-to-micro" transformation due to a pH-responsive lipid fusion, which makes droplets much more sensitive to ultrasound (US) in contrast-enhanced ultrasound (CEUS) and SDT studies. The nanodrug demonstrates robust bimodal imaging ability through fluorine-19 magnetic resonance imaging (19F MRI) and CEUS bimodal imaging, and it exhibits excellent solubility in aqueous solution with relatively high 19F content and desirable long transverse relaxation time (T2 = 1.072 s), making it suitable for high-performance 19F MRI, in addition to effective accumulation of nanodrugs after tail vein injection. Thus, 19F MRI/CEUS dual imaging is achievable to show adequate time points for US irradiation of tumor sites to induce highly effective SDT, which produces abundant reactive oxygen species (ROS) triggering immunogenic cell death (ICD) to assist ICB-based immunotherapy. The combination treatment design of sonodynamic therapy with immunotherapy effectively inhibited TNBC growth and recurrence, highlighting the promise of multifunctional nanodrugs in treating TNBC.

Triple negative cancer (TNBC) is characterized as an aggressive phenotype lacking a specific therapeutic target. To date, self-illuminating photodynamic therapy (PDT) based on chemiluminescence resonance energy transfer (CRET) has emerged as a potential alternative for TNBC treatment by generating singlet oxygen (1O2), overcoming limitations in light penetration. However, this self-illuminating strategy heavily relies on endogenous hydrogen peroxide (H2O2) and oxygen (O2) within the tumor microenvironment (TME), resulting in inefficient therapeutic performance. In this study, we designed CLT@DPD nanoparticles capable of self-illumination via CRET and TME regulation through self-supplying H2O2 and O2. This nanoparticle was constructed by encapsulating luminol-tetreaphenylporphyrin conjugate (LT) and nanoscale CaO2 with DSPE-PEG 2000 and dioleoylphosphatidylcholine (DOPC). A good accumulation at tumor site was achieved due to enhanced permeability and retention (EPR) effect after intravenous injection of CLT@DP. Responsive to the high H2O2 levels and acidic aqueous conditions of TME, LT can be oxidized to produce 1O2 via CRET, and the CaO2 can be decomposed to supply H2O2 and O2. Additionally, the presence of DOPC helps to enhance the permeability of the micelle shell under the oxidation of 1O2, thereby accelerating the release of H2O2 and O2. Our proposed nanoparticles exhibit excellent performance in eradicating in situ tumor cells and inhibiting metastasis by simultaneously enhancing self-luminous PDT and alleviating oxygen depletion in TME.

We report the preparation of a small library of copper-based metallenes, such as copperene, brassene, bronzene, cupronickelene and AlCuZn trimetallene, via a cryo-pretreatment assisted liquid phase exfoliation method. To the best of our knowledge, these nanosheets may represent a new category of metallenes. Benefiting from mixed-valence copper-induced oxidative stress and cleavage effects of layered structures, the obtained metallenes could efficiently eliminate drug-resistant bacteria even at a concentration as low as 1 mu g mL-1. Due to the alloy engineering-induced change in the release rate of metal ions, the CuZn metallene exhibited a much better antibacterial ability than the other metallenes and three clinical antibiotics. We believe this work not only expands the category of emerging 2D metallenes, but also proposes a strategy combining 2D and alloy engineering to improve the antibacterial properties of copper-based materials. We report the preparation of a small library of copper-based metallenes, such as copperene, brassene, bronzene, cupronickelene and AlCuZn trimetallene, via a cryo-pretreatment assisted liquid phase exfoliation method.

AbstractGiven that tumor microenvironment (TME) exerts adverse impact on the therapeutic response and clinical outcome, robust TME modulators may significantly improve the curative effect and increase survival benefits of cancer patients. Here, Au nanodots‐anchored CoFe2O4 nanoflowers with PEGylation (CFAP) are developed to respond to TME cues, aiming to exacerbate redox dyshomeostasis for efficacious antineoplastic therapy under ultrasound (US) irradiation. After uptake by tumor cells, CFAP with glucose oxidase (GOx)‐like activity can facilitate glucose depletion and promote the production of H2O2. Multivalent elements of Co(II)/Co(III) and Fe(II)/Fe(III) in CFAP display strong Fenton‐like activity for·OH production from H2O2. On the other hand, energy band structure CFAP is superior for US‐actuated 1O2 generation, relying on the enhanced separation and retarded recombination of e−/h+ pairs. In addition, catalase‐mimic CFAP can react with cytosolic H2O2 to generate molecular oxygen, which may increase the product yields from O2‐consuming reactions, such as glucose oxidation and sonosensitization processes. Besides the massive production of reactive oxygen species, CFAP is also capable of exhausting glutathione to devastate intracellular redox balance. Severe immunogenic cell death and effective inhibition of solid tumor by CFAP demonstrates the clinical potency of such heterogeneous structure and may inspire more relevant designs for disease therapy.

In the field of skin wound treatment, traditional methods are often limited by the dual challenges of effectively clearing bacterial infections and accelerating wound healing. To address these issues, this study developed an innovative bioactive hydrogel that combines photothermally responsive antimicrobial and immunomodulatory effects. The hydrogel utilized methacrylated gelatin and oxidized dextran, forming a stable network structure through radical and Schiff bonds, loaded with black phosphorus (BP) nanosheets and curcumin (Cur). Characterization of the hydrogel's physicochemical properties revealed not only its excellent swellability, biodegradability, mechanical strength, thermal stability, and antioxidative properties but also its ability to control the release of Cur through the photothermal effect. Under 808 nm NIR irradiation, the suitable photothermal effect was observed with BP nanosheets at a concentration of 250 mu g/mL under a power density of 1.5 W/cm2, and the photothermal conversion efficiency (eta) was 41.34%. In vitro experiments showed that the hydrogel exhibited a bactericidal rate of over 90% against E. coli, S. aureus, and P. aeruginosa and more than 80% antibiofilm formation activity. After coculturing with HUVEC cells for 24 and 48 h, cell viability remained above 80%. Cell migration assay confirmed the hydrogel's effectiveness in promoting cell migration (closure rate reached 97.4% within 24 h). In a rat model with infected wounds, it was shown that on day 14, wounds were nearly healed, with an antibacterial rate of over 85%, the expression levels of proinflammatory factors TNF-alpha and IFN-gamma were reduced, the expression of anti-inflammatory factors IL-4 and TGF-beta 1 was increased, re-epithelialization was observed, and collagen was deposited, which facilitated the rapid healing of the wounds. The hydrogel in this study with photothermal and immunomodulatory capabilities offers an efficient strategy for treating infected wounds.

Tumor starvation therapy utilizing glucose oxidase (GOx), has gained traction due to its non-invasive and bio-safe attributes. However, its effectiveness is often hampered by severe hypoxia in the tumor microenvironment (TME), limiting GOx's catalytic activity. To address this issue, a multifunctional nanosystem based on mesoporous polydopamine nanoparticles (MPDA NPs) was developled to alleviate TME hypoxia. This nanosystem integrated GOx modification and oxygenated perfluoropentane (PFP) encapsulation to address hypoxia-related challenges in the TME. Under NIR laser irradiation, the MPDA NPs exhibit significant photothermal conversion efficacy, activating targeted tumor photothermal therapy (PTT), while also serving as proficient photoacoustic (PA) imaging agents. The ensuing temperature rise facilitates oxygen (O2 2 ) release and induces liquid-gas conversion of PFP, generating microbubbles for enhanced ultrasound (US) imaging signals. The supplied oxygen alleviates local hypoxia, thereby enhancing GOx-mediated endogenous glucose consumption for tumor starvation. Overall, the integration of ultrasound/photoacoustic dual imaging-guided PTT and starvation therapy within MPDA-GOx@PFP@O2 2 nanoparticles (MGPO NPs) presents a promising platform for enhancing the efficacay of tumor treatment by overcoming the complexities of the TME. Statement of significance A multifunctional MPDA-based theranostic nanoagent was developed for US/PAI imaging-guided PTT and starvation therapy against tumor hypoxia by direct O2 2 delivery. The incorporation of oxygenated perfluoropentane (PFP) within the mesoporous structure of MGPO not only enables efficient US imaging but also helps in alleviating tumor hypoxia. Moreover, the strong near-infrared (NIR) absorption of MGPO NPs promote the generation of PFP microbubbles and release of oxygen, thereby enhancing US imaging and GOx-mediated starvation therapy. Such a multifunctional nanosystem leverages synergistic effects to enhance therapeutic efficacy while incorporating US/PA imaging for precise visualization of the tumor. (c) 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.