Piezoelectric Bilayer Nickel-Iron Layered Double Hydroxide Nanosheets with Tumor Microenvironment Responsiveness for Intensive Piezocatalytic Therapy.

Piezocatalytic therapy (PCT) based on 2D layered materials has emerged as a promising non-invasive tumor treatment modality, offering superior advantages. However, a systematic investigation of PCT, particularly the mechanisms underlying the reactive oxygen species (ROS) generation by 2D nanomaterials, is still in its infancy. Here, for the first time, biodegradable piezoelectric 2D bilayer nickel-iron layered double hydroxide (NiFe-LDH) nanosheets (thickness of ≈1.86 nm) are reported for enhanced PCT and ferroptosis. Under ultrasound irradiation, the piezoelectric semiconducting NiFe-LDH exhibits a remarkable ability to generate superoxide anion radicals, due to the formation of a built-in electric field that facilitates the separation of electrons and holes. Notably, the significant excitonic effect in the ultrathin NiFe-LDH system enables long-lived excited triplet excitons (lifetime of ≈5.04 µs) to effectively convert triplet O2 molecules into singlet oxygen. Moreover, NiFe-LDH exhibited tumor microenvironment (TME)-responsive peroxidase (POD)-like and glutathione (GSH)-depleting capabilities, further enhancing oxidative stress in tumor cells and inducing ferroptosis. To the best of knowledge, this is the first report on piezoelectric semiconducting sonosensitizers based on LDHs for PCT and ferroptosis, providing a comprehensive understanding of the piezocatalysis mechanism and valuable references for the application of LDHs and other 2D materials in cancer therapy.

Destruction of vascular endothelial glycocalyx during formation of pre-metastatic niches.

A special microenvironment called the "pre-metastatic niche" is thought to help primary tumor cells migrate to new tissues and invade them, in part because the normal barrier function of the vascular endothelium is compromised. While the primary tumor itself can promote the creation of such niches by secreting pro-metastatic factors, the underlying molecular mechanisms are still poorly understood. Here, we show that the injection of primary tumor-secreted pro-metastatic factors from B16F10 melanoma or 4T1 breast cancer cells into healthy mice can induce the destruction of the vascular endothelial glycocalyx, which is a polysaccharide coating on the vascular endothelial lumen that normally inhibits tumor cell passage into and out of the circulation. However, when human umbilical vein endothelial cultures were treated in vitro with these secreted pro-metastatic factors, no significant destruction of the glycocalyx was observed, implying that this destruction requires a complex in vivo microenvironment. The tissue section analysis revealed that secreted pro-metastatic factors could clearly upregulate macrophage-related molecules such as CD11b and tumor necrosis factor-α (TNF-α) in the heart, liver, spleen, lung, and kidney, which is associated with the upregulation and activation of heparanase. In addition, macrophage depletion significantly attenuated the degradation of the vascular endothelial glycocalyx induced by secreted pro-metastatic factors. This indicates that the secreted pro-metastatic factors that destroy the vascular endothelial glycocalyx rely primarily on macrophages. Our findings suggest that the formation of pre-metastatic niches involves degradation of the vascular endothelial glycocalyx, which may hence be a useful target for developing therapies to inhibit cancer metastasis.

Survival analysis and development of a prognostic nomogram for patients with hepatitis B virus-associated hepatocellular carcinoma.

Background and aims: Hepatitis B virus (HBV) is a common cause of hepatocellular carcinoma (HCC) in China, and this study aimed to identify high-risk factors for overall survival and develop a nomogram prediction model. Methods: In the present retrospective cohort study, patients with HBV-associated HCC diagnosed from January 2009 to December 2018 were enrolled. Their clinical characteristics and time-to-event information were retrieved from electronic medical records. The zero time was the date of HCC diagnosis, and the endpoint was death or liver transplantation. Multivariable COX proportional hazard regression was used to screen independent risk factors for overall survival; then a nomogram model was developed to predict the survival probability of HCC patients. Results: A total of 1723 patients were enrolled, with 82.7 % male and a median age of 54.0 years. During a median follow-up time of 41.3 months, 672 cases (39.0 %) died. Age ≥60 years (HR = 1.209), Male (HR = 1.293), ALB <35 g/L (HR = 1.491), AST ≥80 U/L (HR = 1.818); AFP 20-400 ng/mL (HR = 2.284), AFP ≥400 ng/mL (HR = 2.746); LSM 9-22 kPa (HR = 2.266), LSM ≥22 kPa (HR = 4.326); BCLC stage B/C (HR = 4.079) and BCLC stage D (HR = 16.830) were the independent high-risk factors associated with HCC survival. A prognostic nomogram with a consistency index of 0.842 (95 % CI: 0.827-0.858) was developed. The calibration curve for long-term survival rate fitted well. Conclusions: This study identified independent risk factors affecting the survival of patients with HBV-associated HCC and constructed a predictive nomogram model, which can individually predict the overall survival and has good clinical application value.

Assessment of intestinal status in MPLW515L mutant myeloproliferative neoplasms mice model.

The MPLW515L mutation is a prevalent genetic mutation in patients with myeloproliferative neoplasms (MPN), and utilizing this mutation in mice model can provide important insights into the disease. However, the relationship between intestinal homeostasis and MPN mice model remains elusive. In this study, we utilized a retroviral vector to transfect hematopoietic stem cells with the MPLW515L mutation, creating mutated MPN mice model to investigate their intestinal status. Our results revealed that the MPLW515L in MPN mice model aggravated inflammation in the intestines, decreased the levels of tight junction proteins and receptors for bacteria metabolites. Additionally, there was increased activation of the caspase1/IL-1ß signaling pathway and a significant reduction in phos-p38 levels in the intestinal tissue in MPN mice. The MPLW515L mutation also led to up-expression of anti-microbial genes in the intestinal tract. Though the mutation had no impact on the alpha diversity and dominant bacterial taxa, it did influence the rare bacterial taxa/sub-communities and consequently impacted intestinal homeostasis. Our findings demonstrate the significance of MPLW515L mice model for studying MPN disease and highlight the mutation's influence on intestinal homeostasis, including inflammation, activation of the IL-1ß signaling pathway, and the composition of gut microbial communities.

Proximal tubular Bmal1 protects against chronic kidney injury and renal fibrosis by maintaining of cellular metabolic homeostasis.

Recent studies suggest that deletion of the core clock gene Bmal1 in the kidney has a significant influence on renal physiological functions. However, the role of renal Bmal1 in chronic kidney disease (CKD) remains poorly understood. Here by generating mice lacking Bmal1 in proximal tubule (Bmal1flox/flox-KAP-Cre+, ptKO) and inducing CKD with the adenine diet model, we found that lack of Bmal1 in proximal tubule did not alter renal water and electrolyte homeostasis. However, adenine-induced renal injury indexes, including blood urea nitrogen, serum creatinine, and proteinuria, were markedly augmented in the ptKO mice. The ptKO kidneys also developed aggravated tubulointerstitial fibrosis and epithelial-mesenchymal transformation. Mechanistically, RNAseq analysis revealed significant downregulation of the expression of genes related to energy and substance metabolism, in particular fatty acid oxidation and glutathione/homocysteine metabolism, in the ptKO kidneys. Consistently, the renal contents of ATP and glutathione were markedly reduced in the ptKO mice, suggesting the disruption of cellular metabolic homeostasis. Moreover, we demonstrated that Bmal1 can activate the transcription of cystathionine ß-synthase (CBS), a key enzyme for homocysteine metabolism and glutathione biosynthesis, through direct recruitment to the E-box motifs of its promoter. Supporting the in vivo findings, knockdown of Bmal1 in cultured proximal tubular cells inhibited CBS expression and amplified albumin-induced cell injury and fibrogenesis, while glutathione supplementation remarkably reversed these changes. Taken together, we concluded that deletion of Bmal1 in proximal tubule may aggravate chronic kidney injury and exacerbate renal fibrosis, the mechanism is related to suppressing CBS transcription and disturbing glutathione related metabolic homeostasis. These findings suggest a protective role of Bmal1 in chronic tubular injury and offer a novel target for treating CKD.

Antioxidative and Cytoprotective Effects of Ganoderma applanatum and Fomitopsis pinicola in PC12 Adrenal Phaeochromocytoma Cells.

Considering the impact of oxidative stress on the development of many diseases, together with the role of natural antioxidants in maintaining physiological balance in humans, medicinal mushrooms are potential sources of bioactive compounds against many diseases. In the present work, in vitro evaluation of the biological activities of the alcoholic extracts of two wild tree mushrooms, namely, Ganoderma applanatum and Fomitopsis pinicola, has been performed. Extraction of G. applanatum (GAE) and F. pinicola (FPE) was conducted with 60% ethanol and 100% ethanol sequentially. UPLC-MS/MS identification was conducted on the two mushrooms extracts. A total of 15 substances were identified in GAE, including 3 spiro meroterpenoids and 12 triterpenoids; a total of 14 chemical constituents were iden¬tified in FPE, including 8 triterpenoids, 4 triterpene glycosides, 1 lanosterol, and 1 lanostanoid. The resulting extracts were examined for their in vitro antioxidative and cytoprotective effects against AAPH-induced oxidative damage. Our results demonstrated that both extracts have potent antioxidative activities, when GAE was 0.2 mg/mL, the clearance rates of DPPH and ABTS have reached 93.34% and 99.93%, respectively. When FPE was 1.4 mg/mL and 0.6 mg/mL, the scavenging rates of DPPH and ABTS have reached 91.76% and 100%, respectively. Both the alcoholic extracts of G. applanatum and F. pinicola were able to protect the AAPH-induced damage and could effectively inhibit cell aging via ß-galactosidase (SA ß-gal) staining activity test and scanning electron microscopy analysis.

A patent and literature review of CDK12 inhibitors.

INTRODUCTION: Cyclin-dependent kinase 12 (CDK12) belongs to the CDK family of serine/threonine protein kinases and is associated with cyclin K to exert its biological functions, including regulating gene transcription, mRNA processing, and translation. Increasing evidences demonstrate the importance of CDK12 in various human cancers, illustrating its potential as both biomarker and therapeutic target. In addition, CDK12 is also a promising target for the treatment of myotonic dystrophy type 1. Efforts have been taken to discover small molecule inhibitors to validate this important therapeutic target. AREAS COVERED: This review covers the patented CDK12 inhibitors from 2016 to present, as well as these from peer-reviewed literature. It provides the reader an update of the discovery strategies, chemical structures, and molecular profiling of all available CDK12 inhibitors. EXPERT OPINION: CDK12 inhibitors with various mechanism of actions have been discovered, and it is a great set of tools to evaluate the therapeutic potential of CDK12 in different disease models. CDK12 inhibitors have shown promising results in myotonic dystrophy type 1 mouse model and several preclinical cancer models either as single agent or combination with other anti-cancer agents. Its therapeutic value awaits more rigorous preclinical testing and further clinical investigation.

Polysaccharides in Selenium-Enriched Tea: Extraction Performance under Innovative Technologies and Antioxidant Activities.

Pulsed electric fields (PEF) and ultrasonic-assisted extraction (UE) were applied to improve the extraction performance of selenium-enriched tea polysaccharides (Se-TPSs) in mild conditions. Two combined extraction processes were investigated: (1) PEF strength at 10 kV/cm followed by conventional extraction (CE) at 50 °C for 60 min and (2) PEF+UE (PEF strength at 10 kV/cm followed by UE at 400 W for 60 min). The optimal extraction yields, and energy consumption rates were obtained at 36.86% and 41.53% and 78.78 kJ/mg and 133.91 kJ/mg, respectively. The Se-TPSs were analyzed and characterized by GPC, UV, and FT-IR, which evidenced the structural stability of the Se-TPSs during the extraction processes. It was found that PEF and UE could reduce the particle size diameter of the Se-TPS extract, as well as the proportion of uronic acid. Moreover, PEF could increase the selenium content in the Se-TPS extract by 160.14% due to a lower extraction temperature compared to conventional extraction. The antioxidant activities of the Se-TPSs in vitro were investigated using OH, O2-, and ABTS+ scavenging experiments, as well as a total antioxidant ability evaluation. It was found that the antioxidant activity of the Se-TPSs obtained using PEF2+CE2 was relatively high due to the potential synergistic effect between the selenium and polysaccharides. Based on these results, we speculate that PEF2+CE2 was the best extraction process for the Se-TPSs. Furthermore, this research indicates the application of selenium-enriched tea for functional food production.

Erratum: Tumor Theranostics of Transition Metal Ions Loaded Polyaminopyrrole Nanoparticles: Erratum.

[This corrects the article DOI: 10.7150/ntno.25119.].

Study of Contact Electrification at Liquid-Gas Interface.

It is known that the suspended liquid droplets in clouds can generate electrostatic charges, which finally results in the lightning. However, the detailed mechanism related to the contact-electrification process on the liquid-gas (L-G) interfaces is still poorly understood. Here, by introducing an acoustic levitation method for levitating a liquid droplet, we have studied the electrification mechanism at the L-G interface. The tribo-motion between water droplets and air induced by the ultrasound wave leads to the generation of positive charges on the surface of the droplets, and the charge amount of water droplets (20 µL) gradually reaches saturation within 30 s. The mixed solid particles in droplets can increase the amount of transferred charge, whereas the increase of ion concentration in the droplet can suppress the charge generation. This charge transfer phenomenon at L-G interfaces and the related analysis can be a guidance for the study in many fields, including anti-static, harvesting rainy energy, micro/nano fluidics, triboelectric power generator, surface engineering, and so on. Moreover, the surface charge generation due to L-G electrification is an inevitable effect during ultrasonic levitation, and thus, this study can also work for the applications of the ultrasonic technique.

The role of surgery on the primary tumor site in bladder cancer with distant metastasis: significance of histology type and metastatic pattern.

Due to the limited data and research on bladder cancer with distant metastasis, the role of surgery on the primary tumor site in metastatic bladder cancer has been controversial. The aim of this study was to investigate the impact of surgery on patients with metastatic bladder cancer and to identify any factors correlated with the treatment efficacy. Using the Surveillance, Epidemiology and End Results dataset, we performed a large population-based retrospective study. We classified patents with distant metastasis into subgroups according to their histology type and metastatic pattern. Propensity score matching (PSM) was used to balance clinical variables bias in a 1:3 ratio. A total of 2470 patients with distant metastasis were identified from 2010 to 2016. After PSM, the study eventually included 1068 patients in the surgery group and 356 patients in the non-surgery group. The histologic types, the number of metastatic sites, liver metastasis, surgery, and chemotherapy were significant prognostic variables for patients with distant metastasis before and after PSM. In terms of histologic types, the survival of patients with transitional cell papillary carcinoma, transitional cell non-papillary carcinoma and adenocarcinoma can be improved by surgery alone, while the survival of patients with squamous cell carcinoma can be improved only by combining chemotherapy and surgery. In terms of the number of metastatic sites, surgery alone was an independent prognostic factor in patients with 1 or 2 metastatic sites. In terms of the specificity of metastatic organs, surgery affected overall survival for patients with bone metastasis only, liver metastasis only and lung metastasis only, but for distant lymph nodes metastasis only. It may be helpful to classify patients with bladder cancer and distant metastasis into different groups by integrating variables including histology types and metastatic patterns to choose appropriate treatment strategies.

Multidrug resistant tumors-aimed theranostics on the basis of strong electrostatic attraction between resistant cells and nanomaterials.

Chemotherapy is one of the most common and effective ways for the clinical treatment of tumors, but tumor cells develop resistance toward drugs after a long period of chemotherapy. Interestingly, the gene expression of resistant cells usually generates increased sialic acid and raises the negative potential of the cell membranes, which is potentially useful to design novel theranostic models. In this work, we demonstrate multidrug resistant tumors-aimed theranostics by the virtue of the strong electrostatic attraction between resistant cells and nanomaterials. Human oral epithelial carcinoma vincristine-resistant tumor (KBV) and human oral epithelial carcinoma tumor (KB) were employed and compared as the tumor models. Polyethylene glycol-coated and Cu(ii) and vincristine codoped polyaniline nanoshuttles (VCR-PEG-CuPani NSs), which possessed multifunctions, positive charges, and blood circulation half-life of 6.26 ± 0.16 h, were employed as the nanomaterials for performing the tumor theranostics. Because of the stronger electrostatic attraction with KBV than that with KB, VCR-PEG-CuPani NSs showed higher enrichment of 8.05 ± 0.39% ID g-1 for KBV and a lower value of 6.02 ± 0.22% ID g-1 for KB. The higher accumulation of VCR-PEG-CuPani NSs in KBV tumors further improved the efficacy of tumor theranostics, such as those using magnetic resonance imaging, chemotherapy, and photothermal therapy.

Tumor Theranostics of Transition Metal Ions Loaded Polyaminopyrrole Nanoparticles.

Polypyrrole (PPy) nanoparticles (NPs) possess high near-infrared absorption and good biosafety, showing the potentials as photothermal therapeutic materials. However, the single function and the weak diagnostic function limit the further combination with other functional units to achieve theranostics. In this work, polyaminopyrrole (PPy-NH2) is demonstrated as the alternative of PPy for preparing NPs. Because of the amino group, metal ions, such as Cu(II) and Fe(III) can be loaded in PPy-NH2 NPs, which extends the applications in multimodal theranostics. Systematical studies reveal that the contribution of Cu(II) in multimodal theranostics is greater than Fe(III). Cu can enhance T1 response signal for magnetic resonance imaging (MRI) and be released controllably in the organism, leading to the effect of chemotherapy. Therefore, Cu(II) and Fe(III) co-loaded PPy-NH2 NPs are defined as CuPPy-NH2 NPs. Experimental results indicate that the optimal size of CuPPy-NH2 NPs is 50.2 nm. The photothermal transduction efficiency is 76.4%. After thermochemotherapy, a complete ablation of human oral epithelial carcinoma tumors is observed. No tumor recurrence is found. Methods: Cu(II) and Fe(III) co-loaded PPy-NH2 NPs are prepared through oxidation polymerization by mixing Py-NH2, CuCl2, and FeCl3 in water under stirring at room temperature, which are defined as CuPPy-NH2 NPs. The as-prepared CuPPy-NH2 NPs are tested with a variety of cell and animal experiments for tumor theranostics. Results: CuPPy-NH2 NPs have good light stability, photothermal stability, biosafety and low toxicity. The optimal size of theranostic CuPPy-NH2 NPs is 50.2 nm, which present a photothermal transduction efficiency of 76.4%. The doped Cu(II) ions also show chemotherapeutic behavior. After thermochemotherapy, a complete ablation of human oral epithelial carcinoma tumors is observed. No tumor recurrence is found. Because of the unpaired electron in Cu atomic orbits, CuPPy-NH2 NPs also show T1-weighted magnetic resonance imaging. Conclusions: This kind of transition metal-doped polymer gives a competitive approach for designing and fabricating multimodal theranostic nanodevices, which shows the potential in tumor treatment.

Cu(II)-Doped Polydopamine-Coated Gold Nanorods for Tumor Theranostics.

Gold nanorods (AuNRs) are potentially useful in tumor theranostics, but the poor stability, high toxicity, and rapid removal by the immune system seriously limit their theranostic applications. In our study, we demonstrate the fabrication of Cu(II)-doped polydopamine-coated AuNR (AuNR@CuPDA), which significantly improves the potentials in tumor theranostics. Besides the improvement of physiological stability and biocompatibility, the PDA shell increases the photothermal performance and prolongs the blood circulation time of AuNRs. The half-life of AuNRs during blood circulation increases from 0.7 to 4.5 h after PDA coating, and the injected dose per gram of tumor tissue is 4.6% ID g-1 for AuNR@CuPDA. In addition to computer tomography imaging, the loading of Cu(II) in PDA shell endows AuNR@CuPDA with magnetic resonance imaging function. Cu(II) doped in PDA shell also exhibits chemotherapeutic behavior, and the tumor inhibitor rate is 31.2%. Further combining 808 nm laser-driven photothermal therapy, tumors were completely ablated, and no recurrence was observed. Liver and renal functions tests and histological analysis of major organs confirm that AuNR@CuPDA is in good safety.

Inhibition of IL-8-mediated endothelial adhesion, VSMCs proliferation and migration by siRNA-TMEM98 suggests TMEM98's emerging role in atherosclerosis.

Transmembrane protein 98 (TMEM98), known as a novel gene related to lung cancer, hepatocellular carcinoma, differentiation of T helper 1 cells and normal eye development, has no defined role reported in terms of atherosclerosis (AS). To investigate the potential involvement of TMEM98 during AS processes, its obvious secretion and expression has been initially characterized in hyperlipidemia patients' serum and AS mice's serum respectively. We then explored the possible role of TMEM98 in the pathogenesis of AS in vitro. IL-8, a pro-atherogenesis cytokine, was used to induce the expression of TMEM98 in both endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). Collectively, TMEM98 expression significantly increased in ECs and VSMCs, both induced by IL-8. Additionally, the adhesion ability of monocytes to ECs as well as the proliferation and migration of VSMCs were all decreased after siRNA-TMEM98 treatment. Furthermore, siRNA-TMEM98 dramatically inhibited the expression of ICAM-1 in ECs and the expression of p-AKT, p-GSK3ß and Cyclin D1 from VSMCs, and AKT agonist partially restored the proliferation and migration of VSMC after siRNA-TMEM98 treatment. Taken together, siRNA-TMEM98 inhibits IL-8 mediated EC adhesion by down-regulating the expression of ICAM-1. Additionally, it also hinders the proliferation and migration of VSMCs through suppressing the AKT/GSK3ß/Cyclin D1 signaling pathway. Our study provides sufficient evidence to support that TMEM98 could be a novel gene associated with AS for the first time.

Cu2+-Loaded Polydopamine Nanoparticles for Magnetic Resonance Imaging-Guided pH- and Near-Infrared-Light-Stimulated Thermochemotherapy.

Cancer multimodal treatment by combining the effects of different theranostics agents can efficiently improve treatment efficacy and reduce side effects. In this work, we demonstrate the theranostics nanodevices on the basis of Cu2+-loaded polydopamine nanoparticles (CuPDA NPs), which are able to offer magnetic resonance imaging (MRI)-guided thermochemotherapy (TCT). Systematical studies reveal that after Cu2+ ions loading, the molar extinction coefficient of PDA NPs is greatly enhanced by 4 times, thus improving the performance in photothermal therapy. Despite Cu2+ ions being toxic, the release of Cu2+ is mainly stimulated in acidic environment. Once the NPs deposit in the slightly acidic tumor microenvironment (pH ≈ 6.5-6.8), the release rate boosts ∼30%, which effectively avoids the systematic toxicity during chemotherapy. Meanwhile, due to the increment of the electron-proton dipole-dipole interaction correlation time τC, the spin-lattice relaxation time (T1) for PDA NPs is found to be shortened by Cu2+ loading, which boosts the longitudinal relaxivity (r1). Hence, CuPDA NPs can be used as T1-weighted contrast agent in MRI. In addition, due to the naturally existing DA in the human body with stealth effect, CuPDA NPs have an outstanding tumor retention rate as high as 8.2% ID/g. Further in vitro and in vivo tests indicate that CuPDA NPs possess long blood circulation time, good photothermal and physiological stability, and biocompatibility, which are potential nanodevices for MRI-guided TCT with minimal side effects.

Fe3O4@polydopamine Composite Theranostic Superparticles Employing Preassembled Fe3O4 Nanoparticles as the Core.

Iron oxide (Fe3O4), polydopamine (PDA), and in particular their composites are examples of the safest nanomaterials for developing multifunctional nanodevices to perform noninvasive tumor diagnosis and therapy. However, the structures and performances of Fe3O4-PDA nanocomposites should be further perfected to enhance the theranostic efficiency. In this work, we demonstrate the fabrication of PDA-capped Fe3O4 (Fe3O4@PDA) superparticles (SPs) employing preassembled Fe3O4 nanoparticles (NPs) as the cores. Owing to the collective effect of preassembled Fe3O4 NPs, the superparamagnetism and photothermal performance of Fe3O4@PDA SPs are greatly enhanced, thus producing nanodevices with improved magnetic resonance imaging (MRI)-guided photothermal efficiency. Systematical studies reveal that the molar extinction coefficient of the as-assembled Fe3O4 SPs is 3 orders of magnitude higher than that of individual Fe3O4 NPs. Also due to the high aggregation degree of Fe3O4 NPs, the T2-weighted MRI contrast is greatly enhanced for the SPs with r2 relaxivity of 230.5 mM(-1) s(-1), which is ∼2.5 times larger than that of individual Fe3O4 NPs. The photothermal stability, physiological stability, and biocompatibility, as well as the photothermal performance of Fe3O4 SPs, are further improved by enveloping with PDA shell.

Cu(II) doped polyaniline nanoshuttles for multimodal tumor diagnosis and therapy.

Nanodevices for multimodal tumor theranostics have shown great potentials for noninvasive tumor diagnosis and therapy, but the libraries of multimodal theranostic building blocks should be further stretched. In this work, Cu(II) ions are doped into polyaniline (Pani) nanoshuttles (NSs) to produce Cu-doped Pani (CuPani) NSs, which are demonstrated as new multimodal building blocks to perform tumor theranostics. The CuPani NSs are capable of shortening the longitudinal relaxation (T1) of protons under magnetic fields and can help light up tumors in T1-weighted magnetic resonance imaging. In addition, the released Cu(II) ions from CuPani NSs lead to cytotoxicity, showing the behavior of chemotherapeutic agent. The good photothermal performance of CuPani NSs also makes them as photothermal agents to perform thermochemotherapy. By combining near-infrared laser irradiation, a complete tumor ablation is achieved and no tumor recurrence is observed.