Intracellular Criegee's mechanism-based synergistic ozone therapy mediated by oleogels for cancer treatment.

Broad cellular components-initiated efficient chemical reactions that occur in malignant cells may contribute to exploring emerging strategies for cancer treatment. Herein, an ozonated oleogel (OG(O)) was developed to achieve cancer ozone therapy (O3-T) based on intracellular Criegee's reaction. By integrating the chemo-drug, the ozone-loaded oleogel (Dox@OG(O)) was prepared as a chemotherapeutic agent for local O3-T, associated with chemotherapy (CT)/radiotherapy (RT)/immunotherapy and wound healing. The in vitro results showed that, Dox@OG(O) could achieve high ozone loading efficiency and ensure its stability. This Oleogel-mediated O3-T could directly destroy tumor cells via intracellular Criegee's reaction occurred on cell membranes, as well as the effects of tumor microenvironment (TME) regulation by the generation of oxygen/reactive oxygen species (ROS) and depletion of glutathione (GSH). Meanwhile, under the stimulation of X-ray, an accelerated free radical's production was observed, further combined with the radio-sensitivity after TME regulation, an effective anti-tumor effect would be achieved. Further on, in vivo results demonstrated that the locally implanted Dox@OG(O) could effectively inhibit the growth of both primary and secondary tumors. Considering these results above, it will serve as inspiration for future studies investigating of O3-T, especially for postoperative skin diseases.

FePd Nanozyme- and SKN-Encapsulated Functional Lipid Nanoparticles for Cancer Nanotherapy via ROS-Boosting Necroptosis.

Cell necroptosis has presented great potential, acting as an effective approach against tumor apoptotic resistance, and it could be further enhanced via accompanying reactive oxygen species (ROS) overexpression. However, whether overproduced ROS assists the necroptotic pathway remains unclear. Thus, iron-palladium nanozyme (FePd NZ)- and shikonin (SKN)-encapsulated functional lipid nanoparticles (FPS-LNPs) were designed to investigate the ROS overexpression-enhanced SKN-induced necroptosis. In this system, SKN acts as an effective necroptosis inducer for cancer cells, and FePd NZ, a sensitive Fenton reaction catalyst, produces extra-intracellular ROS to reinforce the necroptotic pathway. Both in vitro and in vivo antitumor evaluation revealed that FPS-LNPs presented the best tumor growth inhibition efficacy compared with FP-LNPs or SKN-LNPs alone. Meanwhile, induced necroptosis by FPS-LNPs can further trigger the release of damage-associated molecular patterns (DAMPs) and antigens from dying tumor cells to activate the innate immune response. Taking biosafety into consideration, this study has provided a potential nanoplatform for cancer nanotherapy via inducing necroptosis to avoid apoptosis resistance and activate CD8+ T cell immune response.

Cancer nutritional-immunotherapy with NIR-II laser-controlled ATP release based on material repurposing strategy.

Enlightened by the great success of the drug repurposing strategy in the pharmaceutical industry, in the current study, material repurposing is proposed where the performance of carbonyl iron powder (CIP), a nutritional intervention agent of iron supplement approved by the US FDA for iron deficiency anemia in clinic, was explored in anti-cancer treatment. Besides the abnormal iron metabolic characteristics of tumors, serving as potential targets for CIP-based cancer therapy under the repurposing paradigm, the efficacy of CIP as a catalyst in the Fenton reaction, activator for dihydroartemisinin (DHA), thus increasing the chemo-sensitivity of tumors, as well as a potent agent for NIR-II photothermal therapy (PTT) was fully evaluated in an injectable alginate hydrogel form. The CIP-ALG gel caused a rapid temperature rise in the tumor site under NIR-II laser irradiation, leading to complete ablation in the primary tumor. Further, this photothermal-ablation led to the significant release of ATP, and in the bilateral tumor model, both primary tumor ablation and inhibition of secondary tumor were observed simultaneously under the synergistic tumor treatment of nutritional-photothermal therapy (NT/PTT). Thus, material repurposing was confirmed by our pioneering trial and CIP-ALG-meditated NT/PTT/immunotherapy provides a new choice for safe and efficient tumor therapy.

Apoptosis and Paraptosis Induced by Disulfiram-Loaded Ca2+/Cu2+ Dual-Ions Nano Trap for Breast Cancer Treatment.

Regarded as one of the hallmarks of tumorigenesis and tumor progression, the evasion of apoptotic cell death would also account for treatment resistance or failure during cancer therapy. In this study, a Ca2+/Cu2+ dual-ion "nano trap" to effectively avoid cell apoptosis evasion by synchronously inducing paraptosis together with apoptosis was successfully designed and fabricated for breast cancer treatment. In brief, disulfiram (DSF)-loaded amorphous calcium carbonate nanoparticles (NPs) were fabricated via a gas diffusion method. Further on, the Cu2+-tannic acid metal phenolic network was embedded onto the NPs surface by self-assembling, followed by mDSPE-PEG/lipid capping to form the DSF-loaded Ca2+/Cu2+ dual-ions "nano trap". The as-prepared nanotrap would undergo acid-triggered biodegradation upon being endocytosed by tumor cells within the lysosome for Ca2+, Cu2+, and DSF releasing simultaneously. The released Ca2+ could cause mitochondrial calcium overload and lead to hydrogen peroxide (H2O2) overexpression. Meanwhile, Ca2+/reactive oxygen species-associated mitochondrial dysfunction would lead to paraptosis cell death. Most importantly, cell paraptosis could be further induced and strengthened by the toxic dithiocarbamate (DTC)-copper complexes formed by the Cu2+ combined with the DTC, the metabolic products of DSF. Additionally, the released Cu2+ will be reduced by intracellular glutathione to generate Cu+, which can catalyze the H2O2 to produce a toxic hydroxyl radical by a Cu+-mediated Fenton-like reaction for inducing cell apoptosis. Both in vitro cellular assays and in vivo antitumor evaluations confirmed the cancer therapeutic efficiency by the dual ion nano trap. This study can broaden the cognition scope of dual-ion-mediated paraptosis together with apoptosis via a multifunctional nanoplatform.

A Biodegradable, Adhesive, and Stretchable Hydrogel and Potential Applications for Allergic Rhinitis and Epistaxis.

Bioadhesive hydrogels have attracted considerable attention as innovative materials in medical interventions and human-machine interface engineering. Despite significant advances in their application, it remains critical to develop adhesive hydrogels that meet the requirements for biocompatibility, biodegradability, long-term strong adhesion, and efficient drug delivery vehicles in moist conditions. A biocompatible, biodegradable, soft, and stretchable hydrogel made from a combination of a biopolymer (unmodified natural gelatin) and stretchable biodegradable poly(ethylene glycol) diacrylate is proposed to achieve durable and tough adhesion and explore its use for convenient and effective intranasal hemostasis and drug administration. Desirable hemostasis efficacy and enhanced therapeutic outcomes for allergic rhinitis are accomplished. Biodegradation enables the spontaneous removal of materials without causing secondary damage and minimizes medical waste. Preliminary trials on human subjects provide an essential foundation for practical applications. This work elucidates material strategies for biodegradable adhesive hydrogels, which are critical to achieving robust material interfaces and advanced drug delivery platforms for novel clinical treatments.

Physical Dissolution Combined with Photodynamic Depletion: A Two-Pronged Nanoapproach for Deoxygenation-Driven and Hypoxia-Activated Prodrug Therapy.

Hypoxia may enhance the chemoresistance of cancer cells and can significantly compromise the effectiveness of chemotherapy. Many efforts have been made to relieve or reverse hypoxia by introducing more oxygen into the tumor microenvironment (TME). Acting in a diametrically opposite way, in the current study, a novel nanocarrier was designed to further exhaust the oxygen level of the hypoxic TME. By creating such an oxygen depleted TME, the hypoxia-selective cytotoxin can work effectively, and oxygen exhaustion triggered chemotherapy can be achieved. Herein, deoxygenation agent, FDA-approved perfluorocarbon (PFC) and photosensitizer indocyanine green (ICG) for oxygen depletion, along with the hypoxia-activating drug tirapazamine (TPZ), were coincorporated within the poly(lactic-co-glycolic acid) (PLGA) nanoemulsion (ICG/TPZ@PPs) for the treatment of hypoxic tumors. Following hypoxia amplifying through physical oxygen dissolution and photodynamic depletion in tumors, hypoxic chemotherapy could be effectively activated to improve multitreatment synergy. After achieving local tumor enrichment, PFC-mediated oxygen dissolution combined with further ICG-mediated photodynamic therapy (PDT) under near-infrared (NIR) laser irradiation could induce enhanced hypoxia, which would activate the antitumor activity of codelivered TPZ to synergize cytotoxicity. Remarkably, in vivo experimental results exhibited that deoxygenated ICG/TPZ@PPs-based photothermal therapy (PTT), PDT, and hypoxia activated chemotherapy have an excellent synergistic ablation of tumors without obvious side effects, and therefore, a broad prospect of application of this nanocarrier could be expected.

Thermoresponsive hydrogel for transcatheter arterial chemoembolization of hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is one of the most commonly used treatments for hepatocellular carcinoma (HCC); however, the poor stability of emulsified chemotherapy drugs by iodinated oil always leads to serious systemic cytotoxicity. Herein, a composite hydrogel Epi/Etpoil@MC/XG was proposed by stably distributing ethiodized poppyseed oil (Etpoil) and epirubicin (Epi) in the blend hydrogel of methylcellulose (MC) and xanthan gum (XG). Benefiting from its adjusted thermo-responsive and injectable properties, the Epi/Etpoil@MC/XG has been successfully applied in the embolization of the feeding artery for a VX2 tumor model.

Acidity-Triggered Charge-Convertible Conjugated Polymer for Dihydroartemisinin Delivery and Tumor-Specific Chemo-Photothermal Therapy.

Since the nonspecificity and nonselectivity of traditional treatment models lead to the difficulty of cancer treatment, nanobased strategies are needed to fill in the gaps of current approaches. Herein, a tumor microenvironment (TME)-responsive chemo-photothermal treatment model was developed based on dihydroartemisinin (DHA)-loaded conjugated polymers (DHA@PLGA-PANI). The synthesized DHA@PLGA-PANI exhibited enhanced photothermal properties under mild-acidic conditions and thus triggered local heat at the tumor site. Meanwhile, these iron-doped conjugated polymers of PLGA-PANI were used as the source of Fe, and benefiting from the Fe-dependent cytotoxicity of DHA, the burst of free radicals could be generated in tumors. Therefore, the combination of TME-responsive chemo-photothermal therapy could achieve effective tumor efficacy.

Nanoheterostructure by Liquid Metal Sandwich-Based Interfacial Galvanic Replacement for Cancer Targeted Theranostics.

Nanoheterostructures with exquisite interface and heterostructure design find numerous applications in catalysis, plasmonics, electronics, and biomedicine. In the current study, series core-shell metal or metal oxide-based heterogeneous nanocomposite have been successfully fabricated by employing sandwiched liquid metal (LM) layer (i.e., LM oxide/LM/LM oxide) as interfacial galvanic replacement reaction environment. A self-limiting thin oxide layer, which would naturally occur at the metal-air interface under ambient conditions, could be readily delaminated onto the surface of core metal (Fe, Bi, carbonyl iron, Zn, Mo) or metal oxide (Fe3 O4 , Fe2 O3 , MoO3 , ZrO2 , TiO2 ) nano- or micro-particles by van der Waals (vdW) exfoliation. Further on, the sandwiched LM layer could be formed immediately and acted as the reaction site of galvanic replacement where metals (Au, Ag, and Cu) or metal oxide (MnO2 ) with higher reduction potential could be deposited as shell structure. Such strategy provides facile and versatile approaches to design and fabricate nanoheterostructures. As a model, nanocomposite of Fe@Sandwiched-GaIn-Au (Fe@SW-GaIn-Au) is constructed and their application in targeted magnetic resonance imaging (MRI) guided photothermal tumor ablation and chemodynamic therapy (CDT), as well as the enhanced radiotherapy (RT) against tumors, have been systematically investigated.

Age-related changes in the ratio of Type I/III collagen and fibril diameter in mouse skin.

The content of type I collagen (COL-I) and type III collagen (COL-III) and the ratio between them not only affect the skin elasticity and mechanical strength, but also determine the fibril diameter. In this research, we investigated the age-related changes in COL-I/COL-III ratio with their formed fibril diameter. The experimental result was obtained from high performance liquid chromatography-mass spectrometer, hydroxyproline determination, picrosirius red staining and transmission electron microscopes (TEM), respectively. The result indicated that the COL-I/COL-III ratio in mouse skin increased with aging. From the 0th to 9th week, the COL-I/COLIII ratio increased from 1.3:1 to 4.5:1. From the 9th to the 18th week, it remained between 4.5:1 and 4.9:1. The total content of COL-I and COL-III firstly increased and then decreased with aging. The TEM result showed that the fibril diameter increased with aging. From the 0th to 9th week, the average fibril diameter increased from 40 to 112 nm; From the 9th to 18th weeks, it increased from 112 to 140 nm. After the 9th week. The fibril diameter showed obvious uneven distribution. Thus, the COL-I/COLIII ratio was proportional to the fibril diameter, but inversely proportional to the uniformity of fibril diameter.

Sequentially activating macrophages M1 and M2 phenotypes by lipopolysaccharide-containing Mg-Fe layered double hydroxides coating on the Ti substrate.

As cells of innate immunity, macrophages are a class of innate immune cells existing in almost all tissues and play a crucial role in bone repair. However, it remains a challenge to modulate the sequential activation of the deferent phenotypes in macrophage when designing the titanium (Ti) implants. In this study, the Mg-Fe layered double hydroxides (LDHs) was coated on Ti substrate through hydrothermal treatment. Further on lipopolysaccharide (LPS) was introduced onto the LDHs through adsorption and ions exchange. The adsorption efficiency of the coating on LPS reached 72.8% in 24 h due to the anion exchange and electrostatic interactions between the LPS and the LDH layers in deionized water. The LDHs-LPS coating released a large amount of LPS in the early stage, which induced macrophages into M1 phenotype via activating TLR-4 → MyD88 and TLR-4 → Ticam-1/2 signal pathways. Subsequently, the M1 macrophages were transformed into M2 phenotype by regulating the integrin α5ß1 of cells by the nanostructures, wetting angle and Mg2+ of the coating. The LDHs-LPS coating endows Ti with the ability of stage immunomodulation, indicating the positive osteoimmunomodulatory property.

Hypoxia Alleviated and One Photo-Triggered Thermal/Dynamic Nanoplatform for Immunogenic Cell Death-Initiated Cancer Immunotherapy.

Immunogenic cell death (ICD) induced by treatment modalities like chemotherapy, radiotherapy, and photothermal and photodynamic therapy has shown great potential to improve the low response rate of various solid tumors in cancer immunotherapy. However, extensive studies have revealed that the efficacy of cancer treatment is limited by the hypoxia and immunosuppression in the tumor microenvironment (TME). To address these challenges, a hypoxia alleviated and one phototriggered thermal/dynamic nanoplatform based on MnO2@PDA/ICG-BSA (MPIB) is developed for oxygen (O2) self-supply enhanced cancer phototherapy (PT). First, MnO2 transfers intracellular overexpression H2O2 into O2 in the acidic TME through its catalase-like activity to improve the hypoxia and also provide O2 for the following photodynamic therapy. Then, under single NIR-808 nm light irradiation (called the "phototherapeutic window"), excellent photothermal and photodynamic performance of the MPIB is activated for combined PT. Finally, assisted with immune adjuvant cytosine-phospho-guanine, obvious ICD and systemic antitumor immunity was elicited in PT-treated mice and demonstrated significant growth inhibition on distant tumors. This MPIB-based nanoplatform highlights the promise to overcome the limitations of hypoxia and also challenges of immunosuppressive tumor microenvironments for improved cancer immunotherapy.

Shape-controllable and kinetically miscible Copper-Palladium bimetallic nanozymes with enhanced Fenton-like performance for biocatalysis.

Bimetallic nanozymes have been emerging as essential catalysts due to their unique physicochemical properties from the monometallics. However, the access to optimize catalytic performance is often limited by the thermodynamic immiscibility and also heterogeneity. Thus, we present a one-step coreduction strategy to prepare the miscible Cu-Pd bimetallic nanozymes with controllable shape and homogeneously alloyed structure. The homogeneity is systematically explored and luckily, the homogeneous introduction of Cu successfully endows Cu-Pd bimetallic nanozymes with enhanced Fenton-like efficiency. Density functional theory (DFT) theoretical calculation reveals that Cu-Pd bimetallic nanozymes exhibit smaller d-band center compared with Pd nanozymes. Easier adsorption of H2O2 molecular contributed by the electronic structure of Cu significantly accelerate the catalytic process together with the strong repulsive interaction between H atom and Pd atom. In vitro cytotoxicity and intracellular ROS generation performance reveal the potential for in vivo biocatalysis. The strategy to construct kinetically miscible Cu-Pd bimetallic nanozymes will guide the development of bimetallic catalysts with excellent Fenton-like efficiency for biocatalytic nanomedicine.

A flexible and highly sensitive organic electrochemical transistor-based biosensor for continuous and wireless nitric oxide detection.

As nitric oxide (NO) plays significant roles in a variety of physiological processes, the capability for real-time and accurate detection of NO in live organisms is in great demand. Traditional assessments of NO rely on indirect colorimetric techniques or electrochemical sensors that often comprise rigid constituent materials and can hardly satisfy sensitivity and spatial resolution simultaneously. Here, we report a flexible and highly sensitive biosensor based on organic electrochemical transistors (OECTs) capable of continuous and wireless detection of NO in biological systems. By modifying the geometry of the active channel and the gate electrodes of OECTs, devices achieve optimum signal amplification of NO. The sensor exhibits a low response limit, a wide linear range, high sensitivity, and excellent selectivity, with a miniaturized active sensing region compared with a conventional electrochemical sensor. The device demonstrates continuous detection of the nanomolar range of NO in cultured cells for hours without significant signal drift. Real-time and wireless measurement of NO is accomplished for 8 d in the articular cavity of New Zealand White rabbits with anterior cruciate ligament (ACL) rupture injuries. The observed high level of NO is associated with the onset of osteoarthritis (OA) at the later stage. The proposed device platform could provide critical information for the early diagnosis of chronic diseases and timely medical intervention to optimize therapeutic efficacy.

Ultrafast Fabrication of Iron/Manganese Co-Doped Bismuth Trimetallic Nanoparticles: A Thermally Aided Chemodynamic/Radio-Nanoplatform for Low-Dose Radioresistance.

Low-dose radioresistance continues to be one of the major limitations for clinical curative treatment of cancer. Luckily, nanotechnology mediated by multifunctional nanomaterials provides potential opportunity to relieve the radioresistance via increasing the radiosensitivity of cancer cells. Herein, an ultrafast fabrication strategy is reported to prepare iron/manganese co-doped bismuth trimetallic nanoparticles (pFMBi NPs) as a multifunctional radiosensitizer for combined therapy. The bismuth matrix provides the intrinsic radiosensitization effect under the low and safe radiation dose via Auger electrons, photoelectrons, and Rayleigh scattering. Meanwhile, co-doping of iron and manganese ions endows pFMBi NPs with both the Fenton reaction property for reactive oxygen species (ROS) generation and photothermal conversion performance for heat production. Additional ROS generation enhances the radiosensitization effect by collaborating with Rayleigh scattering-mediated water radiolysis, and endogenous heat production under near-infrared 808 nm laser irradiation makes DNA more sensitive to radiation and ROS damage. Both in vitro and in vivo evaluations demonstrate the effective antitumor and radiosensitization effects via thermally aided chemodynamic/radiotreatment with a low radiation dose (6 Gy). Therefore, this work provides a potential strategy for overcoming the low-dose radioresistance in cancer therapy.

Correction: All-purpose nanostrategy based on dose deposition enhancement, cell cycle arrest, DNA damage, and ROS production as prostate cancer radiosensitizer for potential clinical translation.

Correction for 'All-purpose nanostrategy based on dose deposition enhancement, cell cycle arrest, DNA damage, and ROS production as prostate cancer radiosensitizer for potential clinical translation' by Xiao-xiao Guo et al., Nanoscale, 2021, 13, 14525-14537, https://doi.org/10.1039/D1NR03869A.

Local Destruction of Tumors for Systemic Immunoresponse: Engineering Antigen-Capturing Nanoparticles as Stimulus-Responsive Immunoadjuvants.

Immunotherapy has established a new paradigm for cancer treatment and made many breakthroughs in clinical practice. However, the rarity of immune response suggests that additional intervention is necessary. In recent years, it has been reported that local tumor destruction (LTD) can cause cancer cell death and induce an immunologic response. Thus, the combination of immunotherapy and LTD methods will be a promising approach to improve immune efficiency for cancer treatment. Herein, a nanobiotechnology platform to achieve high-precision LTD for systemic cancer immunotherapy has been successfully constructed. Possessing radio-sensitizing and photothermal properties, the engineered immunoadjuvant-loaded nanoplatform, which could precisely induce radiotherapy (RT)/photothermal therapy (PTT) to eliminate local tumor and meanwhile lead to the release of tumor-derived protein antigens (TDPAs), has been facilely fabricated by commercialized SPG membrane emulsification technology. Further on, the TDPAs could be captured and form personal nanovaccines in situ to serve as both reservoirs of antigen and carriers of immunoadjuvant, which can effectively improve the immune response. The investigations suggest that the combination of RT/PTT and improved immunotherapy using adjuvant-encapsulated antigen-capturing nanoparticles holds tremendous promise in cancer treatments.

All-purpose nanostrategy based on dose deposition enhancement, cell cycle arrest, DNA damage, and ROS production as prostate cancer radiosensitizer for potential clinical translation.

Radiotherapy (RT) is one of the main treatments for men with prostate cancer (PCa). To date, numerous sophisticated nano-formulations as radiosensitizers have been synthesized with inspiring therapeutic effects both in vitro and in vivo; however, almost all the attention has been paid on the enhanced dose deposition effect by secondary electrons of nanomaterials with high atomic numbers (Z); despite this, cell-cycle arrest, DNA damage, and also reactive oxygen species (ROS) production are critical working mechanisms that account for radiosensitization. Herein, an 'all-purpose' nanostrategy based on dose deposition enhancement, cell cycle arrest, and ROS production as prostate cancer radiosensitizer for potential clinical translation was proposed. The rather simple structure of docetaxel-loaded Au nanoparticles (NPs) with prostate specific membrane antigen (PSMA) ligand conjugation have been successfully synthesized. Enhanced cellular uptake achieved via the selective internalization of the NPs by PCa cells with positive PSMA expression could guarantee enhanced dose deposition. Moreover, the as-synthesized nanosystem could effectively arrest the cell cycle at G2/M phases, which would reduce the ability of DNA damage repair for more irradiation sensitive of the PCa cells. Moreover, the G2/M phase arrest would further promote cascade retention and the enrichment of NPs within the cells. Furthermore, ROS generation and double strand breaks greatly promoted by NPs under irradiation (IR) could also provide an underlying basis for effective radiosensitizers. In vitro and in vivo investigations confirmed the as-synthesized NPs as an effective nano-radiosensitizer with ideal safety. More importantly, all moieties within the present nanosystem have been approved by FDA for the purpose of PCa treatment, thus making it highly attractive for clinical translation.

Hypoxia-Overcoming Breast-Conserving Treatment by Magnetothermodynamic Implant for a Localized Free-Radical Burst Combined with Hyperthermia.

For the purpose of improving the quality of life and minimizing the psychological morbidity of a mastectomy, breast-conserving treatment (BCT) has become the more preferable choice in breast cancer patients. Meanwhile, tumor hypoxia has been increasingly recognized as a major deleterious factor in cancer therapies. In the current study, a novel, effective, and noninvasive magnetothermodynamic strategy based on an oxygen-independent free-radical burst for hypoxia-overcoming BCT is proposed. Radical precursor (AIPH) and iron oxide nanoparticles (IONPs) are coincorporated within the alginate (ALG) hydrogel, which is formed in situ within the tumor tissue by leveraging the cross-linking effect induced by the local physiological Ca2+ with ALG solution. Inductive heating is mediated by IONPs under AMF exposure, and consequently, regardless of the tumor hypoxia condition, a local free-radical burst is achieved by thermal decomposition of AIPH via AMF responsivity. The combination of magnetic hyperthermia and oxygen-irrelevant free-radical production effectively enhances the in vitro cytotoxic effect and also remarkably inhibits tumor proliferation. This study provides a valuable protocol for an hypoxia-overcoming strategy and also an alternative formulation candidate for noninvasive BCT.

Ferrous ions doped layered double hydroxide: smart 2D nanotheranostic platform with imaging-guided synergistic chemo/photothermal therapy for breast cancer.

Developing simple and efficient nanotheranostic platforms with behavior responsive to the acid microenvironment of a tumor is of great significance for accurate tumor diagnosis and therapy. In this study, a smart 2D nanotheranostic platform has been successfully fabricated by doping functional ferrous ions into as-synthesized MgAl-layered double hydroxide (LDH) with doxurubicin (DOX) loading to form Fe-LDH/DOX NPs, which achieved magnetic resonance imaging (MRI)-guided synergistic chemo/photothermal therapy for breast cancer. The doping of ferrous ions into Fe-LDH/DOX enabled a strong photo-induced heating ability with a high photothermal conversion efficiency of 45.67%, which could be combined with the antitumor drug DOX to achieve the synergistic effect of photothermal therapy (PTT) and chemotherapy for killing tumor cells. Additionally, its in vitro pH-dependent degradation behavior and T2-weighted MRI effect revealed that the as-prepared Fe-LDH/DOX is sensitive to the tumor acid microenvironment. Most importantly, the growth rate of tumors in 4T1 bearing mice could be effectively inhibited after the synergistic treatment of PTT and chemotherapy by Fe-LDH/DOX. These results show that doping functional metal ions into LDH NPs may open a novel approach to fabricating an LDH NP-based nanotheranostics platform with advanced diagnostic and therapeutic performances.