First Affiliated Hospital of Soochow University

The aberrant Wnt/β-catenin signaling pathway facilitates cancer stem cell renewal, cell proliferation and differentiation, thus exerting crucial roles in tumorigenesis and therapy response. Accumulated investigations highlight the therapeutic potential of agents targeting Wnt/β-catenin signaling in cancer. Wnt ligand/ receptor interface, β-catenin destruction complex and TCF/β-catenin transcription complex are key components of the cascade and have been targeted with interventions in preclinical and clinical evaluations. This scoping review aims at outlining the latest progress on the current approaches and perspectives of Wnt/β-catenin signaling pathway targeted therapy in various cancer types. Better understanding of the updates on the inhibitors, antagonists and activators of Wnt/β-catenin pathway rationalizes innovative strategies for personalized cancer treatment. Further investigations are warranted to confirm precise and secure targeted agents and achieve optimal use with clinical benefits in malignant diseases.

Bone is the second most commonly transplanted tissue worldwide, with over four million operations using bone grafts or bone substitute materials annually to treat bone defects. However, significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma, cancer, infection and arthritis. Developing bioactive three-dimensional (3D) scaffolds to support bone regeneration has therefore become a key area of focus within bone tissue engineering (BTE). A variety of materials and manufacturing methods including 3D printing have been used to create novel alternatives to traditional bone grafts. However, individual groups of materials including polymers, ceramics and hydrogels have been unable to fully replicate the properties of bone when used alone. Favourable material properties can be combined and bioactivity improved when groups of materials are used together in composite 3D scaffolds. This review will therefore consider the ideal properties of bioactive composite 3D scaffolds and examine recent use of polymers, hydrogels, metals, ceramics and bio-glasses in BTE. Scaffold fabrication methodology, mechanical performance, biocompatibility, bioactivity, and potential clinical translations will be discussed.

Mesenchymal stem cells (MSCs), a non-hematopoietic stem cell population first discovered in bone marrow, are multipotent cells capable of differentiating into mature cells of several mesenchymal tissues, such as fat and bone. As common progenitor cells of adipocytes and osteoblasts, MSCs are delicately balanced for their differentiation commitment. Numerous in vitro investigations have demonstrated that fat-induction factors inhibit osteogenesis, and, conversely, bone-induction factors hinder adipogenesis. In fact, a variety of external cues contribute to the delicate balance of adipo-osteogenic differentiation of MSCs, including chemical, physical, and biological factors. These factors trigger different signaling pathways and activate various transcription factors that guide MSCs to commit to either lineage. The dysregulation of the adipo-osteogenic balance has been linked to several pathophysiologic processes, such as aging, obesity, osteopenia, osteopetrosis, and osteoporosis. Thus, the regulation of MSC differentiation has increasingly attracted great attention in recent years. Here, we review external factors and their signaling processes dictating the reciprocal regulation between adipocytes and osteoblasts during MSC differentiation and the ultimate control of the adipo-osteogenic balance.

In this work, a nanoscale reduced graphene oxide–iron oxide nanoparticle (RGO–IONP) complex is noncovalently functionalized with polyethylene glycol (PEG), obtaining a RGO–IONP–PEG nanocomposite with excellent physiological stability, strong NIR optical absorbance, and superparamagnetic properties. Using this theranostic nanoprobe, in-vivo triple modal fluorescence, photoacoustic, and magnetic resonance imaging are carried out, uncovering high passive tumor targeting, which is further used for effective photothermal ablation of tumors in mice. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

BACKGROUND: In acute ischemic stroke, there is uncertainty regarding the benefit and risk of administering intravenous alteplase before endovascular thrombectomy. METHODS: We conducted a trial at 41 academic tertiary care centers in China to evaluate endovascular thrombectomy with or without intravenous alteplase in patients with acute ischemic stroke. Patients with acute ischemic stroke from large-vessel occlusion in the anterior circulation were randomly assigned in a 1:1 ratio to undergo endovascular thrombectomy alone (thrombectomy-alone group) or endovascular thrombectomy preceded by intravenous alteplase, at a dose of 0.9 mg per kilogram of body weight, administered within 4.5 hours after symptom onset (combination-therapy group). The primary analysis for noninferiority assessed the between-group difference in the distribution of the modified Rankin scale scores (range, 0 [no symptoms] to 6 [death]) at 90 days on the basis of a lower boundary of the 95% confidence interval of the adjusted common odds ratio equal to or larger than 0.8. We assessed various secondary outcomes, including death and reperfusion of the ischemic area. RESULTS: Of 1586 patients screened, 656 were enrolled, with 327 patients assigned to the thrombectomy-alone group and 329 assigned to the combination-therapy group. Endovascular thrombectomy alone was noninferior to combined intravenous alteplase and endovascular thrombectomy with regard to the primary outcome (adjusted common odds ratio, 1.07; 95% confidence interval, 0.81 to 1.40; P = 0.04 for noninferiority) but was associated with lower percentages of patients with successful reperfusion before thrombectomy (2.4% vs. 7.0%) and overall successful reperfusion (79.4% vs. 84.5%). Mortality at 90 days was 17.7% in the thrombectomy-alone group and 18.8% in the combination-therapy group. CONCLUSIONS: In Chinese patients with acute ischemic stroke from large-vessel occlusion, endovascular thrombectomy alone was noninferior with regard to functional outcome, within a 20% margin of confidence, to endovascular thrombectomy preceded by intravenous alteplase administered within 4.5 hours after symptom onset. (Funded by the Stroke Prevention Project of the National Health Commission of the People's Republic of China and the Wu Jieping Medical Foundation; DIRECT-MT ClinicalTrials.gov number, NCT03469206.).

PURPOSE: To study the role of infiltrating neutrophils in the development of experimental corneal neovascularization (CNV). METHODS: CNV was induced by alkali injury in normal C57BL/6 mice, and the kinetics of neutrophil recruitment to the cornea and the CNV was detected by histologic analysis at multiple time points. Neutrophil recruitment to the corneas was inhibited by injection of anti-mouse granulocyte monoclonal antibodies (Ly-6G) or neutralizing anti-mouse CXCR2 antibodies. CNV was compared between the control and the specific antibody-treated mice 2 weeks after alkali injury, as quantified by CD31 immunostaining. Corneal vascular endothelial growth factor (VEGF) expression after injury was determined by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical staining. RESULTS: Many myeloperoxidase-positive neutrophils began to infiltrate the corneas 2 days after injury, but infiltration ceased by 14 days after injury. CNV became evident 7 days after injury, reached a maximal level at 14 days, and decreased thereafter. The mRNA expression of CXCR2 and its ligands, macrophage inflammatory protein 2 (CXCL2/MIP-2), and growth-related protein alpha (CXCL1/KC) increased markedly at 2 days after injury. Injection of either anti-mouse granulocyte monoclonal antibodies (Ly-6G) or neutralizing anti-mouse CXCR2 antibodies markedly, and to a similar extent, inhibited neutrophil recruitment to the cornea, indicating that neutrophil infiltration was mediated primarily by CXCR2. In contrast, these treatments failed to attenuate alkali-induced CNV. VEGF mRNA expression was enhanced 2 days after injury, and VEGF proteins were detected mainly in infiltrating mononuclear cells but not in neutrophils. CONCLUSIONS: CXCR2-mediated neutrophil infiltration contributes only marginally to the subsequent development of CNV.

We report here that mouse macrophages undergo receptor-interacting kinase-3 (RIP3)-dependent but TNF-α-independent necrosis when Toll-like receptors (TLR) 3 and 4 are activated by poly(I:C) and LPS, respectively. An adaptor protein, Toll/IL-1 receptor domain-containing adapter inducing IFN-β (TRIF/TICAM-1), which is dispensable for TNF-α-induced necrosis, forms a complex with RIP3 upon TLR3/TLR4 activation and is essential for TLR3/TLR4-induced necrosis. Mice without RIP3 or functional TRIF did not show macrophage loss and elevation of inflammatory cytokines when they were exposed to LPS. Necrosis in mouse macrophages induced by either TNFR or TLR3/TLR4 is executed by reactive oxygen species. Taken together, these data indicate that there are multiple upstream necrosis-initiating signaling pathways converging on the RIP3 during an innate immune response to viral and bacterial infections in mammals.

Enhanced near-field at noble metal nanoparticle surfaces due to localized surface plasmon resonance (LSPR) has been researched in fields ranging from biomedical to photoelectrical applications. However, it is rarely explored on nonmetallic nanomaterials discovered in recent years, which can also support LSPR by doping-induced free charge carriers, let alone the investigation of an intricate system involving both. Here we construct a dual plasmonic hybrid nanosystem Au-Cu9S5 with well controlled interfaces to study the coupling effect of LSPR originating from the collective electron and hole oscillations. Cu9S5 LSPR is enhanced by 50% in the presence of Au, and the simulation results confirm the coupling effect and the enhanced local field as well as the optical power absorption on Cu9S5 surface. This enhanced optical absorption cross section, high photothermal transduction efficiency (37%), large light penetration depth at 1064 nm, excellent X-ray attenuation ability, and low cytotoxicity enable Au-Cu9S5 hybrids for robust photothermal therapy in the second near-infrared (NIR) window with low nanomaterial dose and laser flux, making them potential theranostic nanomaterials with X-ray CT imaging capability. This study will benefit future design and optimization of photoabsorbers and photothermal nanoheaters utilizing surface plasmon resonance enhancement phenomena for a broad range of applications.

BACKGROUND: During the spring of 2013, a novel avian-origin influenza A (H7N9) virus emerged and spread among humans in China. Data were lacking on the clinical characteristics of the infections caused by this virus. METHODS: Using medical charts, we collected data on 111 patients with laboratory-confirmed avian-origin influenza A (H7N9) infection through May 10, 2013. RESULTS: Of the 111 patients we studied, 76.6% were admitted to an intensive care unit (ICU), and 27.0% died. The median age was 61 years, and 42.3% were 65 years of age or older; 31.5% were female. A total of 61.3% of the patients had at least one underlying medical condition. Fever and cough were the most common presenting symptoms. On admission, 108 patients (97.3%) had findings consistent with pneumonia. Bilateral ground-glass opacities and consolidation were the typical radiologic findings. Lymphocytopenia was observed in 88.3% of patients, and thrombocytopenia in 73.0%. Treatment with antiviral drugs was initiated in 108 patients (97.3%) at a median of 7 days after the onset of illness. The median times from the onset of illness and from the initiation of antiviral therapy to a negative viral test result on real-time reverse-transcriptase-polymerase-chain-reaction assay were 11 days (interquartile range, 9 to 16) and 6 days (interquartile range, 4 to 7), respectively. Multivariate analysis revealed that the presence of a coexisting medical condition was the only independent risk factor for the acute respiratory distress syndrome (ARDS) (odds ratio, 3.42; 95% confidence interval, 1.21 to 9.70; P=0.02). CONCLUSIONS: During the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death. (Funded by the National Natural Science Foundation of China and others.).

Jack of all trades: A multifunctional nanoparticle (MFNP) integrates an upconversion nanoparticle (see picture, green), a layer of iron oxide nanoparticles (black), and a gold shell (red). The system can be used for in vitro targeted upconversion luminescence, magnetic resonance, and light scattering multimodal imaging of cells. The near-infrared optical absorption of MFNPs also enables photothermal destruction of cancer cells.

BACKGROUND: The gastric intramucosal pH (pHi) and gastric mucosal-arterial CO2 gap (GAP) estimate visceral perfusion and predict outcome. Threshold values of these variables for use during resuscitation, however, remain poorly defined. The purpose of this study was to develop clinically derived cutoffs for both pHi and GAP for predicting death and multiple organ failure (MOF) in trauma patients. METHODS: This was a cohort study of 114 consecutive trauma patients who had pHi determined at 24 hours after intensive care unit admission. The corresponding GAP for each of these values of pHi was obtained through chart review. Receiver operating characteristic curves were constructed for both pHi and GAP with respect to death and MOF. These curves were used to determine the value of each variable that maximized the sum of sensitivity and specificity in predicting outcome. chi2 tests and odds ratios were used to determine if significant differences in outcome occurred above and below these cutoff values. RESULTS: Of 114 patients who had pHi determined at 24 hours after admission, 108 had corresponding GAP values available. The values of pHi and GAP that maximized sensitivity and specificity were 7.25 and 18 mm Hg, respectively. The odds ratio for pHi versus death was 4.6 and for pHi versus MOF was 4.3. The odds ratios for GAP versus death and MOF were 2.9 and 3.3, respectively. CONCLUSION: In trauma patients, the ability to predict death and MOF is maximized at values of pHi less than 7.25 and GAP greater than 18 mm Hg. These values represent clinically derived cutoffs that should be useful for evaluating the adequacy of intestinal perfusion during resuscitation.

Two-dimensional graphene and its composite nanomaterials offer interesting physical/chemical properties and have been extensively explored in a wide range of fields in recent years. In this work, we synthesize a multi-functional superparamagnetic graphene oxide-iron oxide hybrid nanocomposite (GO-IONP), which is then functionalized by a biocompatible polyethylene glycol (PEG) polymer to acquire high stability in physiological solutions. A chemotherapy drug, doxorubicin (DOX), was loaded onto GO-IONP-PEG, forming a GO-IONP-PEG-DOX complex, which enables magnetically targeted drug delivery. GO-IONP-PEG also exhibits strong optical absorbance from the visible to the near-infrared (NIR) region, and can be utilized for localized photothermal ablation of cancer cells guided by the magnetic field. Moreover, for the first time, in vivo magnetic resonance (MR) imaging of tumor-bearing mice is also demonstrated using GO-IONP-PEG as the T 2 contrast agent. Our work suggests the promise of using multifunctional GO-based nanocomposites for applications in cancer theranostics.

Hypoxia not only promotes tumor metastasis but also strengthens tumor resistance to therapies that demand the involvement of oxygen, such as radiation therapy and photodynamic therapy (PDT). Herein, taking advantage of the high reactivity of manganese dioxide (MnO 2 ) nanoparticles toward endogenous hydrogen peroxide (H 2 O 2 ) within the tumor microenvironment to generate O 2 , multifunctional chlorine e6 (Ce6) loaded MnO 2 nanoparticles with surface polyethylene glycol (PEG) modification (Ce6@MnO 2 ‐PEG) are formulated to achieve enhanced tumor‐specific PDT. In vitro studies under an oxygen‐deficient atmosphere uncover that Ce6@MnO 2 ‐PEG nanoparticles could effectively enhance the efficacy of light‐induced PDT due to the increased intracellular O 2 level benefited from the reaction between MnO 2 and H 2 O 2 , the latter of which is produced by cancer cells under the hypoxic condition. Owing to the efficient tumor homing of Ce6@MnO 2 ‐PEG nanoparticles upon intravenous injection as revealed by T1‐weighted magnetic resonance imaging, the intratumoral hypoxia is alleviated to a great extent. Thus, in vivo PDT with Ce6@MnO 2 ‐PEG nanoparticles even at a largely reduced dose offers remarkably improved therapeutic efficacy in inhibiting tumor growth compared to free Ce6. The results highlight the promise of modulating unfavorable tumor microenvironment with nanotechnology to overcome current limitations of cancer therapies.

Importance: Stroke is the leading cause of death in China. However, recent data about the up-to-date stroke burden in China are limited. Objective: To investigate the urban-rural disparity of stroke burden in the Chinese adult population, including prevalence, incidence, and mortality rate, and disparities between urban and rural populations. Design, Setting, and Participants: This cross-sectional study was based on a nationally representative survey that included 676 394 participants aged 40 years and older. It was conducted from July 2020 to December 2020 in 31 provinces in mainland China. Main Outcomes and Measures: Primary outcome was self-reported stroke verified by trained neurologists during a face-to-face interviews using a standardized protocol. Stroke incidence were assessed by defining first-ever strokes that occurred during 1 year preceding the survey. Strokes causing death that occurred during the 1 year preceding the survey were considered as death cases. Results: The study included 676 394 Chinese adults (395 122 [58.4%] females; mean [SD] age, 59.7 [11.0] years). In 2020, the weighted prevalence, incidence, and mortality rates of stroke in China were 2.6% (95% CI, 2.6%-2.6%), 505.2 (95% CI, 488.5-522.0) per 100 000 person-years, and 343.4 (95% CI, 329.6-357.2) per 100 000 person-years, respectively. It was estimated that among the Chinese population aged 40 years and older in 2020, there were 3.4 (95% CI, 3.3-3.6) million incident cases of stroke, 17.8 (95% CI, 17.5-18.0) million prevalent cases of stroke, and 2.3 (95% CI, 2.2-2.4) million deaths from stroke. Ischemic stroke constituted 15.5 (95% CI, 15.2-15.6) million (86.8%) of all incident strokes in 2020, while intracerebral hemorrhage constituted 2.1 (95% CI, 2.1-2.1) million (11.9%) and subarachnoid hemorrhage constituted 0.2 (95% CI, 0.2-0.2) million (1.3%). The prevalence of stroke was higher in urban than in rural areas (2.7% [95% CI, 2.6%-2.7%] vs 2.5% [95% CI, 2.5%-2.6%]; P = .02), but the incidence rate (485.5 [95% CI, 462.8-508.3] vs 520.8 [95% CI, 496.3-545.2] per 100 000 person-years; P < .001) and mortality rate (309.9 [95% CI, 291.7-328.1] vs 369.7 [95% CI, 349.1-390.3] per 100 000 person-years; P < .001) were lower in urban areas than in rural areas. In 2020, the leading risk factor for stroke was hypertension (OR, 3.20 [95% CI, 3.09-3.32]). Conclusions and Relevance: In a large, nationally representative sample of adults aged 40 years or older, the estimated prevalence, incidence, and mortality rate of stroke in China in 2020 were 2.6%, 505.2 per 100 000 person-years, and 343.4 per 100 000 person-years, respectively, indicating the need for an improved stroke prevention strategy in the general Chinese population.

Abstract Sonodynamic therapy (SDT) triggered by ultrasound (US) has attracted increasing attention owing to its abilities to overcome critical limitations including low tissue‐penetration depth and phototoxicity in photodynamic therapy. Herein, the design of a new type of sonosensitizer is revealed, namely, ultrasmall oxygen‐deficient bimetallic oxide MnWO X nanoparticles, for multimodal imaging‐guided enhanced SDT against cancer. As‐made MnWO X nanoparticles with poly(ethylene glycol) (PEG) modification show high physiological stability and biocompatibility. Interestingly, such MnWO X ‐PEG nanoparticles exhibit highly efficient US‐triggered production of 1 O 2 and •OH, higher than that of previously reported sonosensitizers (e.g., protoporphyrin IX and titanium dioxide), because the oxygen‐deficient structure of MnWO X serves as an electron trap site to prevent electron–hole recombination. The glutathione depletion capability of MnWO X ‐PEG can also further favor SDT‐triggered cancer cell killing. With efficient tumor homing as illustrated by computer tomography and magnetic resonance imaging, MnWO X ‐PEG enables effective destruction of mouse tumors under US stimulation. After accomplishing its therapeutic functions, MnWO X ‐PEG can be metabolized by the mouse body without any long‐term toxicity. Herein, a new type of sono‐sensitizing agent with high SDT efficacy, multimodal imaging functions, and rapid clearance is presented, an agent which is promising for noninvasive SDT cancer treatment.

Mesenchymal stromal cells (MSCs) as a pharmaceutical for ailments characterized by pathogenic autoimmune, alloimmune and inflammatory processes now cover the spectrum of early- to late-phase clinical trials in both industry and academic sponsored studies. There is a broad consensus that despite different tissue sourcing and varied culture expansion protocols, human MSC-like cell products likely share fundamental mechanisms of action mediating their anti-inflammatory and tissue repair functionalities. Identification of functional markers of potency and reduction to practice of standardized, easily deployable methods of measurements of such would benefit the field. This would satisfy both mechanistic research as well as development of release potency assays to meet Regulatory Authority requirements for conduct of advanced clinical studies and their eventual registration. In response to this unmet need, the International Society for Cellular Therapy (ISCT) addressed the issue at an international workshop in May 2015 as part of the 21st ISCT annual meeting in Las Vegas. The scope of the workshop was focused on discussing potency assays germane to immunomodulation by MSC-like products in clinical indications targeting immune disorders. We here provide consensus perspective arising from this forum. We propose that focused analysis of selected MSC markers robustly deployed by in vitro licensing and metricized with a matrix of assays should be responsive to requirements from Regulatory Authorities. Workshop participants identified three preferred analytic methods that could inform a matrix assay approach: quantitative RNA analysis of selected gene products; flow cytometry analysis of functionally relevant surface markers and protein-based assay of secretome. We also advocate that potency assays acceptable to the Regulatory Authorities be rendered publicly accessible in an "open-access" manner, such as through publication or database collection.

Biodegradable metals have attracted considerable attentions in recent years. Besides the early launched biodegradable Mg and Fe metals, Zn, an essential element with osteogenic potential of human body, is regarded and studied as a new kind of potential biodegradable metal quite recently. Unfortunately, pure Zn is soft, brittle and has low mechanical strength in the practice, which needs further improvement in order to meet the clinical requirements. On the other hand, the widely used industrial Zn-based alloys usually contain biotoxic elements (for instance, ZA series contain toxic Al elements up to 40 wt.%), which subsequently bring up biosafety concerns. In the present work, novel Zn-1X binary alloys, with the addition of nutrition elements Mg, Ca and Sr were designed (cast, rolled and extruded Zn-1Mg, Zn-1Ca and Zn-1Sr). Their microstructure and mechanical property, degradation and in vitro and in vivo biocompatibility were studied systematically. The results demonstrated that the Zn-1X (Mg, Ca and Sr) alloys have profoundly modified the mechanical properties and biocompatibility of pure Zn. Zn-1X (Mg, Ca and Sr) alloys showed great potential for use in a new generation of biodegradable implants, opening up a new avenue in the area of biodegradable metals.

The effects of HLA-identical sibling donor (ISD) hematopoietic stem cell transplantation (HSCT) on adults with intermediate- or high-risk acute myeloid leukemia (AML) in the first complete remission (CR1) are well established. Previous single-center studies have demonstrated similar survival after unmanipulated haploidentical donor (HID) vs ISD HSCT for hematologic malignancies. To test the hypothesis that haploidentical HSCT would be a valid option as postremission therapy for AML patients in CR1 lacking a matched donor, we designed a disease-specific, prospective, multicenter study. Between July 2010 and November 2013, 450 patients were assigned to undergo HID (231 patients) or ISD HSCT (219 patients) according to donor availability. Among HID and ISD recipients, the 3-year disease-free survival rate was 74% and 78% (P = .34), respectively; the overall survival rate was 79% and 82% (P = .36), respectively; cumulative incidences of relapse were 15% and 15% (P = .98); and those of the nonrelapse-mortality were 13% and 8% (P = .13), respectively. In conclusion, unmanipulated haploidentical HSCT achieves outcomes similar to those of ISD HSCT for AML patients in CR1. Such transplantation was demonstrated to be a valid alternative as postremission treatment of intermediate- or high-risk AML patients in CR1 lacking an identical donor. This trial was registered at www.chictr.org as #ChiCTR-OCH-10000940.

The presence within bone marrow of a population of mesenchymal stem cells (MSCs) able to differentiate into a number of different mesenchymal tissues, including bone and cartilage, was first suggested by Friedenstein nearly 40 years ago. Since then MSCs have been demonstrated in a variety of fetal and adult tissues, including bone marrow, fetal blood and liver, cord blood, amniotic fluid and, in some circumstances, in adult peripheral blood. MSCs from all of these sources can be extensively expanded in vitro and when cultured under specific permissive conditions retain their ability to differentiate into multiple lineages including bone, cartilage, fat, muscle, nerve, glial and stromal cells. There has been great interest in these cells both because of their value as a model for studying the molecular basis of differentiation and because of their therapeutic potential for tissue repair and immune modulation. However, MSCs are a rare population in these tissues. Here we tried to identify cells with MSC-like potency in human placenta. We isolated adherent cells from trypsin-digested term placentas and examined these cells for morphology, surface markers, and differentiation potential and found that they expressed several stem cell markers. They also showed endothelial and neurogenic differentiation potentials under appropriate conditions. We suggest that placenta-derived cells have multilineage differentiation potential similar to MSCs in terms of morphology and cell-surface antigen expression. The placenta may prove to be a useful source of MSCs.

Multifunctional nanoplatforms that are safe and have multiple therapeutic functions together with imaging capabilities are highly demanded in the development of new cancer theranostic approaches. A number of near-infrared (NIR)-absorbing inorganic nanomaterials, although having shown great promise not only to photothermally ablate tumors but also to enhance the efficacy of other types of therapies, are not biodegradable and would be retained in the body for a long time. Herein, we develop a multifunctional nanocomposite by coating magnetic iron oxide nanoclusters with a near-infrared light-absorbing polymer polypyrrole (PPy), obtaining Fe3O4@PPy core-shell nanoparticles, which after functionalization with polyethylene glycol could be used for imaging-guided, remotely controlled cancer combination therapy. In this system, the Fe3O4 core, which could be gradually decomposed in physiological environments, is useful for magnetically controlled drug delivery as well as a magnetic resonance imaging contrast. The PPy shell, as an organic polymer, is able to load therapeutic molecules with aromatic structures and also exhibits a strong photothermal effect, which can be used to enhance the chemotherapeutic efficacy, showing an outstanding in vivo synergistic antitumor effect. Our work encourages further exploration of light-absorbing polymer-based nanocomposites for cancer combination therapy under remote physical controls.