Nanoscintillator-Mediated X-Ray-Triggered Boosting Transformation of Fe3+ into Fe2+ for Enhancing Tumor Ferroptosis/Immunotherapy

Ferroptosis therapy induced by iron-catalyzed Fenton reaction has offered enormous opportunities for tumor therapy. Unfortunately, high catalytic activity ferrous (Fe²⁺)-based therapeutic agent has remained challenging due to the instability of Fe²⁺. Herein, an X-ray-activated Fe²⁺ supply platform, termed “PFCN”, containing the core of CaWO₄ nanoscintillator to emit ultraviolet (UV) light and Fe₃O₄ decorated on the surface to deliver excessive Fe²⁺ is proposed. Under X-ray excitation, the UV light emitted by CaWO₄ can catalyze ferric (Fe³⁺) to generate Fe²⁺, which further cascades the Fenton reaction to induce highly toxic hydroxyl radicals generation. More importantly, immunogenic cell death-associated immunotherapy is simultaneously triggered during this process. Experiments conducted in vitro and in vivo revealed that X-ray-triggered PFCN shows superior tumor therapeutic efficacy, contributing i) enhanced radiotherapy; ii) X-ray-activated ferroptosis therapy; and iii) ferroptosis/radiotherapy-induced immunotherapy. Besides, PFCN can be utilized as an MR/CT dual-mode imaging contrast agent for tumor diagnosis and treatment monitoring. The study provides a novel example of an X-ray-activated ferrous-regeneration platform for imaging-guided augmenting tumor ferroptosis/immunotherapy     

Rigid Shell Decorated Nanodevice with Fe/H2O2 Supply and Glutathione Depletion Capabilities for Potentiated Ferroptosis and Synergized Immunotherapy

The overexpressed glutathione peroxidase4 (GPX4) and insufficient H₂O₂ in tumor cells weaken ferroptosis therapy and the elicited anticancer immune response. Herein, a rigid metal-polyphenol shell decorated nanodevice ssPPE_Lap@Fe-TA is constructed to successfully overcome the drawbacks of ferroptosis therapy. The ssPPE_Lap@Fe-TA consists of a rigid Fe-TA network-based shell and disulfide-containing polyphosphoester (ssPPE) core with β-lapachone loading. The rigid Fe-TA network-based shell of ssPPE_Lap@Fe-TA enables its efficient internalization by tumor cell and then disintegrates in the acidic endosome/lysosome to initiate Fe³⁺/Fe²⁺ conversion-driven ferroptosis. The ssPPE core will deplete glutathione (GSH) via the disulfide-thiol exchange reaction to inactivate GPX4, and also trigger the release of β-lapachone to significantly increase intracellular H₂O₂ and then promote Fe³⁺-mediated Fenton reaction, eventually achieving strong inhibition of tumor progression. Moreover, ssPPE_Lap@Fe-TA elicites a robust systemic antitumor immune response by promoting dendritic cells (DCs) maturation and T cell infiltration, and synergizes with anti-PD-L1 antibody (a-PD-L1) to strikingly suppress 4T1 tumor growth and lung metastasis.     

Fabricating Aptamer‐Conjugated PEGylated‐MoS2/Cu1.8S Theranostic Nanoplatform for Multiplexed Imaging Diagnosis and Chemo‐Photothermal Therapy of Cancer

Fabricating theranostic nanoparticles combining multimode disease diagnosis and therapeutic has become an emerging approach for personal nanomedicine. However, the diagnostic capability, biocompatibility, and therapeutic efficiency of theranostic nanoplatforms limit their clinic widespread applications. Targeting to the theme of accurate diagnosis and effective therapy of cancer cells, a multifunctional nanoplatform of aptamer and polyethylene glycol (PEG) conjugated MoS₂ nanosheets decorated with Cu_1.8S nanoparticles (ATPMC) is developed. The ATPMC nanoplatform accomplishes photoluminescence imaging, photoacoustic imaging, and photothermal imaging for in vitro and in vivo tumor cells imaging diagnosis. Meanwhile, the ATPMC nanoplatform facilitates selective delivery of gene probe to detect intracellular microRNA aberrantly expressed in cancer cells and anticancer drug doxorubicin (DOX) for chemotherapy. Moreover, the synergistic interaction of MoS₂ and Cu_1.8S renders the ATPMC nanoplatform with superb photothermal conversion efficiency. The ATPMC nanoplatform loaded with DOX displays near‐infrared laser‐induced programmed chemotherapy and advanced photothermal therapy, and the targeted chemo‐photothermal therapy presents excellent antitumor efficiency.     

Core–Satellite Mesoporous Silica–Gold Nanotheranostics for Biological Stimuli Triggered Multimodal Cancer Therapy

A core–satellite nanotheranostic agent with pH‐dependent photothermal properties, pH‐triggered drug release, and H₂O₂‐induced catalytic generation of radical medicine is fabricated to give a selective and effective tumor medicine with three modes of action. The nanocomplex (core–satellite mesoporous silica–gold nanocomposite) consists of amino‐group‐functionalized mesoporous silica nanoparticles (MSN‐NH₂) linked to L‐cysteine‐derivatized gold nanoparticles (AuNPs‐Cys) with bridging ferrous iron (Fe²⁺) ions. The AuNPs‐Cys serve as both removable caps that control drug release (doxorubicin) and stimuli‐responsive agents for selective photothermal therapy. Drug release and photothermal therapy are initiated by the cleavage of Fe²⁺ coordination bonds at low pH and the spontaneous aggregation of the dissociated AuNPs‐Cys. In addition, the Fe²⁺ is able to catalyze the decomposition of hydrogen peroxide abundant in cancer cells by a Fenton‐like reaction to generate high‐concentration hydroxyl radicals (·OH), which then causes cell damage. This system requires two tumor microenvironment conditions (low pH and considerable amounts of H₂O₂) to trigger the three therapeutic actions. In vivo data from mouse models show that a tumor can be completely inhibited after two weeks of treatment with the combined chemo‐photothermal method; the data directly demonstrate the efficiency of the MSN–Fe–AuNPs for tumor therapy.     

Z‐Scheme Heterojunction Functionalized Pyrite Nanosheets for Modulating Tumor Microenvironment and Strengthening Photo/Chemodynamic Therapeutic Effects

A Z‐scheme heterojunction with high electron–hole pairs separation efficacy and enhanced redox potentials exhibits tremendous potential in photonic theranostics, but still remains unexplored and challenging. Herein, novel 2D thermally oxidized pyrite nanosheets (TOPY NSs) with FeS₂ core and Fe₂O₃ shell are fabricated combining ball grinding and two‐step probe sonication assisted liquid exfoliation under different solution and air environments. The Fe₂O₃ shell and Fe³⁺/Fe²⁺ inside TOPY NSs can both damage the tumor microenvironment through glutathione consumption and O₂ production, and produce ·OH by Fenton reaction. More interestingly, a direct Z‐scheme heterojunction based on FeS₂ core and Fe₂O₃ shell is constructed, in which the electrons in the conduction band (CB) of Fe₂O₃ are recombined with the holes in the valence band (VB) of FeS₂, leaving stronger reduction/oxidation potentials in the CB of FeS₂ and the VB of Fe₂O₃. Under irradiation of a 650 nm laser, the generation of ·O₂^? from O₂ and ·OH from OH^? on the CB of FeS₂ and VB of Fe₂O₃, respectively, is largely enhanced. Furthermore, the NSs can be triggered by an 808 nm laser to generate local hyperthermia for photothermal therapy. Moreover, the fluorescent, photoacoustic, and photothermal imaging capabilities of the NSs allow multimodal imaging‐guided cancer treatment.     

Spiky Fe3O4@Au Supraparticles for Multimodal In Vivo Imaging

Nanomaterials with high biocompatibility and efficient photothermal conversion have drawn tremendous attention for tumor diagnosis and treatment. In this study, spiky Fe₃O₄@Au supraparticles (SPs) are used as phototherapy and multimodal imaging agents. The SPs show excellent photothermal and photodynamic therapeutic effects, with a photothermal conversion efficiency of 31%, and allow tumor‐targeted imaging, including computed tomographic, photoacoustic, and magnetic resonance imaging. The SPs show excellent biocompatibility both in vitro and in vivo. Furthermore, because of their remarkable absorption at near‐infrared region, the SPs obliterate a tumor under 808 nm irradiation. With their capacity for highly integrated multimodal imaging and multiple therapeutic functions, SPs are a promising agent for application to clinical practice.     

Boosting H2O2‐Guided Chemodynamic Therapy of Cancer by Enhancing Reaction Kinetics through Versatile Biomimetic Fenton Nanocatalysts and the Second Near‐Infrared Light Irradiation

Fenton reaction–based chemodynamic therapy (CDT) has attracted considerable attention for tumor treatment, because the Fenton reaction can degrade endogenous H₂O₂ within the tumor to form reactive oxygen species (ROS) to kill cancer cells. The kinetics of the Fenton reaction has significantly influenced its treatment efficacy. It is crucial to enhance the reaction kinetics at the maximum H₂O₂ concentration to quickly produce vast amounts of ROS to achieve treatment efficacy, which to date, has not been realized. Herein, reported is an efficacious CDT treatment of breast cancer using biomimetic CS‐GOD@CM nanocatalysts, which are rationally designed to significantly boost the Fenton reaction through improvement of H₂O₂ concentration within tumors, and application of the second near‐infrared (NIR‐II) light irradiation at the maximum concentration, which is monitored by photoacoustic imaging. The biomimetic nanocatalysts are composed of ultra‐small Cu_2?xSe (CS) nanoparticles, glucose oxidase (GOD), and tumor cell membrane (CM). The nanocatalysts can be retained in tumor for more than two days to oxidize glucose and produce an approximately 2.6‐fold increase in H₂O₂ to enhance the Fenton reaction under the NIR‐II irradiation. This work demonstrates for the first time the CDT treatment of cancer enhanced by the NIR‐II light.     

Rattle‐Type Fe3O4@CuS Developed to Conduct Magnetically Guided Photoinduced Hyperthermia at First and Second NIR Biological Windows

A therapeutic carrier in the second near‐infrared (NIR) window is created that features magnetic target, magnetic resonance imaging (MRI) diagnosis, and photothermal therapy functions through the manipulation of a magnet and NIR laser. A covellite‐based CuS in the form of rattle‐type Fe₃O₄@CuS nanoparticles is developed to conduct photoinduced hyperthermia at 808 and 1064 nm of the first and second NIR windows, respectively. The Fe₃O₄@CuS nanoparticles exhibit broad NIR absorption from 700 to 1300 nm. The in vitro photothermal results show that the laser intensity obtained using 808 nm irradiation required a twofold increase in its magnitude to achieve the same damage in cells as that obtained using 1064 nm irradiation. Because of the favorable magnetic property of Fe₃O₄, magnetically guided photothermal tumor ablation is performed for assessing both laser exposures. According to the results under the fixed laser intensity and irradiation spot, exposure to 1064 nm completely removed tumors showing no signs of relapse. On the other hand, 808 nm irradiation leads to effective inhibition of growth that remained nearly unchanged for up to 30 d, but the tumors are not completely eliminated. In addition, MRI is performed to monitor rattle‐type Fe₃O₄@CuS localization in the tumor following magnetic attraction.     

Nanoshells with Targeted Simultaneous Enhancement of Magnetic and Optical Imaging and Photothermal Therapeutic Response

Integrating multiple functionalities into individual nanoscale complexes is of tremendous importance in biomedicine, expanding the capabilities of nanoscale structures to perform multiple parallel tasks. Here, the ability to enhance two different imaging technologies simultaneously—fluorescence optical imaging and magnetic resonance imaging—with antibody targeting and photothermal therapeutic actuation is combined all within the same nanoshell‐based complex. The nanocomplexes are constructed by coating a gold nanoshell with a silica epilayer doped with Fe₃O₄ and the fluorophore ICG, which results in a high T₂ relaxivity (390 mM ^?1 s^?1) and 45× fluorescence enhancement of ICG. Bioconjugate nanocomplexes target HER2+ cells and induce photothermal cell death upon near‐IR illumination.     

Targeted Magnetic Resonance Imaging/Near-Infrared Dual-Modal Imaging and Ferroptosis/Starvation Therapy of Gastric Cancer with Peritoneal Metastasis

Accurate identification and visualization of peritoneal metastases (PM) are clinically essential to improving the prognosis for gastric cancer. However, owing to the multifocal spread of peritoneal metastasis nodules, small size, and close contact with adjacent organs, identifying and completely removing them during surgery is extremely challenging, resulting in cancer treatment failure and recurrence. This study develops a T₁-weighted magnetic resonance imaging (MRI) contrast agent (FeGdNP)-loaded indocyanine green/glucose oxidase (ICG/GOx) with conjugation of an RGD dimer (RGD2) and acid-labile polymer mPEG (FeGdNP-ICG/GOx-RGD2-mPEG). Compared with commercial Magnevist, the proposed FeGdNP-ICG/GOx-RGD2-mPEG shows a two to three-fold higher tumor ΔSNR in MRI of peritoneal metastasis and subcutaneous animal models. Compared with free ICG, the increased fluorescent signal of FeGdNP-ICG/GOx-RGD2-mPEG allows for the detection of tiny tumor metastatic nodules (<3 mm), and the removal of the peritoneum transplanted tumors. Abundant gluconic acid and H₂O₂ are generated during the GOx-mediated glucose depletion process in cancer cells, thereby enhancing Fenton reaction efficiency. Accumulated toxic ·OH can damage the mitochondrial function and induce the release of mitochondrial reactive oxygen species, which activates the ferroptosis pathway. The data indicate the potential of the nanoparticles for MRI preoperative diagnosis, intraoperative fluorescence-guided navigation, and ferroptosis tumor therapy.     

Assembly of Au Plasmonic Photothermal Agent and Iron Oxide Nanoparticles on Ultrathin Black Phosphorus for Targeted Photothermal and Photodynamic Cancer Therapy

Photodynamic therapy (PDT), as a minimally invasive and high‐efficiency anticancer approach, has received extensive research attention recently. Despite plenty of effort devoted to exploring various types of photodynamic agents with strong near‐infrared (NIR) absorbance for PDT and many encouraging progresses achieved in the area, effective and safe photodynamic photosensitizers with good biodegradability and biocompatibility are still highly expected. In this work, a novel nanocomposite has been developed by assembly of iron oxide (Fe₃O₄) nanoparticles (NPs) and Au nanoparticles on black phosphorus sheets (BPs@Au@Fe₃O₄), which shows a broad light absorption band and a photodegradable character. In vitro and in vivo assay indicates that BPs@Au@Fe₃O₄ nanoparticles are highly biocompatible and exhibit excellent tumor inhibition efficacy owing to a synergistic photothermal and photodynamic therapy mediated by a low‐power NIR laser. Importantly, BPs@Au@Fe₃O₄ can anticipatorily suppress tumor growth by visualized synergistic therapy with the help of magnetic resonance imaging (MRI). This work presents the first combination application of the photodynamic and photothermal effect deriving from black phosphorus nanosheets and plasmonic photothermal effect from Au nanoparticles together with MRI from Fe₃O₄ NPs, which may open the new utilization of black phosphorus nanosheets in biomedicine, optoelectronic devices, and photocatalysis.     

Gold‐Coated Fe3O4 Nanoroses with Five Unique Functions for Cancer Cell Targeting,Imaging, and Therapy

The development of nanomaterials that combine diagnostic and therapeutic functions within a single nanoplatform is extremely important for molecular medicine. Molecular imaging with simultaneous diagnosis and therapy will provide the multimodality needed for accurate diagnosis and targeted therapy. Here, gold‐coated iron oxide (Fe₃O₄@Au) nanoroses with five distinct functions are demonstrated, integrating aptamer‐based targeting, magnetic resonance imaging (MRI), optical imaging, photothermal therapy. and chemotherapy into one single probe. The inner Fe₃O₄ core functions as an MRI agent, while the photothermal effect is achieved through near‐infrared absorption by the gold shell, causing a rapid rise in temperature and also resulting in a facilitated release of the anticancer drug doxorubicin carried by the nanoroses. Where the doxorubicin is released, it is monitored by its fluorescence. Aptamers immobilized on the surfaces of the nanoroses enable efficient and selective drug delivery, imaging, and photothermal effect with high specificity. The five‐function‐embedded nanoroses show great advantages in multimodality.     

Self-Assemblies of Fe3O4 Nanocrystals: Toward Nanoscale Precision of Photothermal Effects in the Tumor Microenvironment

Fe₃O₄ nanocrystals are self-assembled into two different conformations: colloidosome and supraball that confer them with distinct properties determining their photo-induced heating capacities. These self-assemblies are assessed for photothermal therapy, an adjuvant strategy for tumor therapy. The tumor microenvironment is a heterogeneous ecosystem including immune cells and the extracellular matrix. The interactions between photothermal therapy agents and the different components of the tumor microenvironment determine the outcome of this therapy. In this study, the fate of both colloidosomes and supraballs within the tumor microenvironment in comparison to their Fe₃O₄ nanocrystal building blocks is revealed. This study highlights how these two hybrid self-assemblies target different compartments of the tumor microenvironment and trigger local photothermal damages that are inaccessible for isolated nanocrystals and not predicted by global temperature measurements.     

GSH-Depleted Nanozymes with Dual-Radicals Enzyme Activities for Tumor Synergic Therapy

Although inspiring progress has been achieved in tumor nanocatalytic therapies based on tailor-made nanozymes for converting hydrogen peroxide into reactive oxygen species (ROS) efficiently, most cytotoxic hydroxyl radicals do not spread far enough within a cell to damage the primary organelles for effective tumor therapy due to their short half-life time (≈1 µs). Developing a novel nanocatalyst platform involving longer half-life time ROS is desired. To this end, Fe₃O₄-Schwertmannite nanocomposites (Fe₃O₄-Sch) with triple-effect tumor therapy are constructed through a facile method. The Schwertmannite shell converts the ^•OH produced by Fe₃O₄ via the Fenton reaction into sulfate radicals with a longer half-life time (30 µs). Combination of dual radicals exhibits overwhelming tumor inhibition efficacy. The nanocomposites also show the multifunctionality of good photothermal efficiency (33.2%) and synergistic oxidative stress amplification upon glutathione biosynthesis (GSH) depletion by the l -buthionine sulfoximine (BSO) molecules loaded in the hollow Fe₃O₄ cores. The comprehensive properties of the nanoplatform including the dual-radical production, Fe₃O₄ nanocrystal mediated PTT, and the BSO mediated GSH depletion result in remarkable tumor inhibition both in vitro and in vivo, which may pave a way to constructing a synergic catalytic nanoplatform for efficient tumor therapy.     

High‐Security Nanocluster for Switching Photodynamic Combining Photothermal and Acid‐Induced Drug Compliance Therapy Guided by Multimodal Active‐Targeting Imaging

High‐security nanoplatform with enhanced therapy compliance is extremely promising for tumor. Herein, using a simple and high‐efficient self‐assembly method, a novel active‐targeting nanocluster probe, namely, Ag₂S/chlorin e6 (Ce6)/DOX@DSPE‐mPEG₂₀₀₀‐folate (ACD‐FA) is synthesized. Experiments indicate that ACD‐FA is capable of specifically labeling tumor and guiding targeting ablation of the tumor via precise positioning from fluorescence and photoacoustic imaging. Importantly, the probe is endowed with a photodynamic “on‐off” effect, that is, Ag₂S could effectively quench the fluorescence of chlorin e6 (89.5%) and inhibit release of ¹O₂ (92.7%), which is conducive to avoid unwanted phototoxicity during transhipment in the body, and only after nanocluster endocytosed by tumor cells could release Ce6 to produce ¹O₂. Moreover, ACD‐FA also achieves excellent acid‐responsive drug release, and exhibits eminent chemo‐photothermal and photodynamic effects upon laser irradiation. Compared with single or two treatment combining modalities, ACD‐FA could provide the best cancer therapeutic effect with a relatively low dose, because it made the most of combined effect from chemo‐photothermal and controlled photodynamic therapy, and significantly improves the drug compliance. Besides, the active‐targeting nanocluster notably reduces nonspecific toxicity of both doxorubicin and chlorin e6. Together, this study demonstrates the potency of a newly designed nanocluster for nonradioactive concomitant therapy with precise tumor‐targeting capability.     

Photothermo-Promoted Nanocatalysis Combined with H2S-Mediated Respiration Inhibition for Efficient Cancer Therapy

Nanocatalytic medicine has emerged as a promising method for the specific cancer therapy by mediating the interaction between tumor microenvironment biomarkers and nanoagents. However, the produced antitumor cell killing molecules, such as reactive oxygen species (ROS), by catalysis are insufficient to inhibit tumor growth. Herein, a novel kind of polyvinyl pyrrolidone modified multifunctional iron sulfide nanoparticles (Fe_1−xS-PVP NPs) is developed via a one-step hydrothermal method, which exhibits high photothermal (PT) conversion efficiency (η = 24%) under the irradiation of 808 nm near-infrared laser. The increased temperature further facilitates the Fenton reaction to generate abundant •OH radicals. More importantly, under an acidic (pH = 6.5) condition within tumor environment, the Fe_1−xS-PVP NPs can in situ produce H₂S gas, which is evidenced to suppress the activity of enzyme cytochrome c oxidase (COX IV) in cancer cells, contributing to inhibit the growth of tumor. Both in vitro and in vivo results demonstrate that the H₂S-mediated gas therapy in combination with PT enhanced ROS achieves excellent antitumor performance, which can open up a new approach for the design of gas-mediated cancer treatment.     

Mesoporous Polydopamine Carrying Manganese Carbonyl Responds to Tumor Microenvironment for Multimodal Imaging‐Guided Cancer Therapy

Multifunctional nanodrugs integrating multiple therapeutic and imaging functions may find tremendous biomedical applications. However, the development of a simple yet potent theranostic nanosystem with a high payload and microenvironment responsiveness enhancing imaging‐guided cancer therapy is still a great challenge. Herein, a kind of MnCO‐entrapped mesoporous polydopamine nanoparticles are developed, which reach a 1.5 mg payload per gram carrier and exhibit marked theranostic capability through effective CO/Mn²⁺ generation and photothermal conversion inside the H⁺ and H₂O₂‐enriched tumor microenvironment, for a magnetic resonance/photoacoustic bimodal imaging‐guided tumor therapy. The multifunctional nanosystem exhibits a biocompatibility highly desirable for in vivo application and superior performance in inhibiting tumor growth and recurrence via combination CO and photothermal therapy.     

Biodegradable Fe(III)@WS2‐PVP Nanocapsules for Redox Reaction and TME‐Enhanced Nanocatalytic,Photothermal, and Chemotherapy

In this study, biocompatible Fe(III) species‐WS₂‐polyvinylpyrrolidone (Fe(III) @ WS₂‐PVP) nanocapsules with enhanced biodegradability and doxorubicin (DOX) loading capacity are one‐pot synthesized. In this nanocapsule, there exists a redox reaction between Fe(III) species and WS₂ to form Fe²⁺ and WO₄^2?. The formed Fe²⁺ could be oxidized to Fe³⁺, which reacts with Fe(III) @ WS₂‐PVP again to continuously produce Fe²⁺ and WO₄^2?. Such a repeated endogenous redox reaction leads to an enhanced biodegradation and DOX release of DOX @ Fe(III) @ WS₂‐PVP. More strikingly, the Fe²⁺ generation and DOX release are further accelerated by the overexpressed H₂O₂ and the mild acidic tumor microenvironment (TME), since H₂O₂ and H⁺ can accelerate the oxidation of Fe²⁺. The continuously generated Fe²⁺ catalyzes a fast Fenton reaction with the innate H₂O₂ in tumor cells and produces abundant highly toxic hydroxyl radicals for nanocatalytic tumor therapy. Together with the high photothermal transforming capability, the DOX @ Fe(III) @WS₂‐PVP nanocapsules successfully achieve the endogenous redox reaction and exogenous TME‐augmented tumor photothermal therapy, chemo and nanocatalytic therapy outcome. The concept of material design can be innovatively extended to the synthesis of biodegradable Fe(III) @ MoS₂‐PVP nanocomposite, thus paving a promising novel way for the rational design of intelligent theranostic agents for highly efficient treatment of cancer.     

PEGylated Polypyrrole Nanoparticles Conjugating Gadolinium Chelates for Dual‐Modal MRI/Photoacoustic Imaging Guided Photothermal Therapy of Cancer

Polypyrrole nanoparticles conjugating gadolinium chelates were successfully fabricated for dual‐modal magnetic resonance imaging (MRI) and photoacoustic imaging guided photothermal therapy of cancer, from a mixture of pyrrole and pyrrole‐1‐propanoic acid through a facile one‐step aqueous dispersion polymerization, followed by covalent attachment of gadolinium chelate, using polyethylene glycol as a linker. The obtained PEGylated poly­pyrrole nanoparticles conjugating gadolinium chelates (Gd‐PEG‐PPy NPs), sized around around 70 nm, exhibited a high T₁ relaxivity coefficient of 10.61 L mm ^?1 s^?1, more than twice as high as that of the relating free Gd³⁺ complex (4.2 L mm ^–1 s^?1). After 24 h intravenous injection of Gd‐PEG‐PPy NPs, the tumor sites exhibited obvious enhancement in both T₁‐weighted MRI intensity and photoacoustic signal compared with that before injection, indicating the efficient accumulation of Gd‐PEG‐PPy NPs due to the introduction of the PEG layer onto the particle surface. In addition, tumor growth could be effectively inhibited after treatment with Gd‐PEG‐PPy NPs in combination with near‐infrared laser irradiation. The passive targeting and high MRI/photo­acoustic contrast capability of Gd‐PEG‐PPy NPs are quite favorable for precise cancer diagnosing and locating the tumor site to guide the external laser irradiation for photothermal ablation of tumors without damaging the surrounding healthy tissues. Therefore, Gd‐PEG‐PPy NPs may assist in better monitoring the therapeutic process, and contribute to developing more effective “personalized medicine,” showing great potential for cancer diagnosis and therapy.