Optical and Electrical Properties of AlxGa1-xN/GaN Epilayers Modulated by Aluminum Content.

AlGaN-based LEDs are promising for many applications in deep ultraviolet fields, especially for water-purification projects, air sterilization, fluorescence sensing, etc. However, in order to realize these potentials, it is critical to understand the factors that influence the optical and electrical properties of the device. In this work, AlxGa1-xN (x = 0.24, 0.34, 0.47) epilayers grown on c-plane patterned sapphire substrate with GaN template by the metal organic chemical vapor deposition (MOCVD). It is demonstrated that the increase of the aluminum content leads to the deterioration of the surface morphology and crystal quality of the AlGaN epitaxial layer. The dislocation densities of AlxGa1-xN epilayers were determined from symmetric and asymmetric planes of the ω-scan rocking curve and the minimum value is 1.01 × 109 cm-2. The (101¯5) plane reciprocal space mapping was employed to measure the in-plane strain of the AlxGa1-xN layers grown on GaN. The surface barrier heights of the AlxGa1-xN samples derived from XPS are 1.57, 1.65, and 1.75 eV, respectively. The results of the bandgap obtained by PL spectroscopy are in good accordance with those of XRD. The Hall mobility and sheet electron concentration of the samples are successfully determined by preparing simple indium sphere electrodes.

Apatinib Plus Toripalimab (Anti-PD1 Therapy) as Second-Line Therapy in Patients With Advanced Gastric or Esophagogastric Junction Cancer: Results From a Randomized, Open-Label Phase II Study.

BACKGROUND: This study aimed to assess the activity of apatinib plus toripalimab in the second line for patients with advanced gastric or esophagogastric junction cancer (GC/EGJC). METHODS: In this open-label, phase II, randomized trial, patients with advanced GC/EGJC who progressed after first-line chemotherapy were enrolled and received 250 mg apatinib per day plus 240 mg toripalimab on day 1 per 3 weeks (arm A) or physician's choice of chemotherapy (PC, arm B). The primary endpoint of this study was the 1-year survival rate. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and safety were assessed as secondary endpoints. RESULTS: Twenty-five patients received apatinib plus toripalimab while 26 were enrolled in arm B. The 1-year survival rates of the 2 groups were 43.3% and 42.3%, respectively (P = .903). The PFS was 2.77 versus 2.33 months (P = .660). The OS was 8.30 versus 9.88 months (P = .539). An objective response was reported in 20.0% of patients in arm A compared to 26.9% in arm B (P = .368), respectively. A total of 6 (24.0%) patients experienced adverse events of grade ≥ 3 in arm A, while 9 (34.6%) patients suffered from adverse events of grade ≥ 3 in arm B. No drug-related deaths occurred in either group. CONCLUSION: Toripalimab plus apatinib treatment in second-line therapy of advanced GC/EGJC showed manageable toxicity but did not improve clinical outcomes relative to PC treatment (ClinicalTrials.gov Identifier: NCT04190745).

Ultrasound-nanovesicles interplay for theranostics.

Nanovesicles (NVs) are widely used in the treatment and diagnosis of diseases due to their excellent vascular permeability, good biocompatibility, high loading capacity, and easy functionalization. However, their yield and in vivo penetration depth limitations and their complex preparation processes still constrain their application and development. Ultrasound, as a fundamental external stimulus with deep tissue penetration, concentrated energy sources, and good safety, has been proven to be a patient-friendly and highly efficient strategy to overcome the restrictions of traditional clinical medicine. Recent research has shown that ultrasound can drive the generation of NVs, increase their yield, simplify their preparation process, and provide direct therapeutic effects and intelligent control to enhance the therapeutic effect of NVs. In addition, NVs, as excellent drug carriers, can enhance the targeting efficiency of ultrasound-based sonodynamic therapy or sonogenetic regulation and improve the accuracy of ultrasound imaging. This review provides a detailed introduction to the classification, generation, and modification strategies of NVs, emphasizing the impact of ultrasound on the formation of NVs and summarizing the enhanced treatment and diagnostic effects of NVs combined with ultrasound for various diseases.

Single-cell transcriptome profiling of primary tumors and paired organoids of pancreatobiliary cancer.

Single-cell RNA-seq (scRNA-seq) and cancer organoid model have shown promise in investigating tumor microenvironment heterogeneity and facilitating chemotherapeutic drug testing to inform treatment selection. It is still unknown whether the scRNA-seq results based on organoid can faithfully reflect the heterogeneity of primary pancreatobiliary cancer. To reveal the similarities and differences between primary tumors and their matched organoids at transcriptome level, we conducted scRNA-seq for paired primary tumors and organoids from one cholangiocarcinoma (CCA) and two pancreatic ductal adenocarcinoma (PDAC) patients. We identified inter-patient and intra-tumor heterogeneity and found that the organoids retained copy number variation (CNV) patterns of primary tumors. There was no significant difference in cancer stem cell (CSC) properties between the primary tumors and the organoids, whereas organoid from one PDAC case had increased mesenchymal-score and decreased epithelial-score compared with the primary tumors. All organoids showed a transition tendency from the classical subtype to the basal-like subtype in the transcriptional level. Organoids and primary tumors differed in metabolic and unfolded protein response (UPR) signatures. In addition, we revealed the heterogeneity of cancer associated fibroblasts (CAFs) and T cells, and explored the developmental trajectory of T cells. Our findings facilitate further understanding of organoid model and confirm its application prospects in pancreatobiliary cancer.

The Landscape of Biomimetic Nanovesicles in Brain Diseases.

Brain diseases, such as brain tumors, neurodegenerative diseases, cerebrovascular diseases, and brain injuries, are caused by various pathophysiological changes, which pose a serious health threat. Brain disorders are often difficult to treat due to the presence of the blood-brain barrier (BBB). Biomimetic nanovesicles (BNVs), including endogenous extracellular vesicles (EVs) derived from various cells and artificial nanovesicles, possess the ability to penetrate the BBB and thus can be utilized for drug delivery to the brain. BNVs, especially endogenous EVs, are widely distributed in body fluids and usually carry various disease-related signal molecules such as proteins, RNA, and DNA, and may also be analyzed to understand the etiology and pathogenesis of brain diseases. This review covers the exhaustive classification and characterization of BNVs and pathophysiological roles involved in various brain diseases, and emphatically focuses on nanotechnology-integrated BNVs for brain disease theranostics, including various diagnosis strategies and precise therapeutic regulations (e.g., immunity regulation, disordered protein clearance, anti-neuroinflammation, neuroregeneration, angiogenesis, and the gut-brain axis regulation). The remaining challenges and future perspectives regarding the nanotechnology-integrated BNVs for the diagnosis and treatment of brain diseases are also discussed and outlined.

Optical and Structural Properties of Aluminum Nitride Epi-Films at Room and High Temperature.

The high-quality aluminum nitride (AlN) epilayer is the key factor that directly affects the performance of semiconductor deep-ultraviolet (DUV) photoelectronic devices. In this work, to investigate the influence of thickness on the quality of the AlN epilayer, two AlN-thick epi-film samples were grown on c-plane sapphire substrates. The optical and structural characteristics of AlN films are meticulously examined by using high-resolution X-ray diffraction (HR-XRD), scanning electron microscopy (SEM), a dual-beam ultraviolet-visible spectrophotometer, and spectroscopic ellipsometry (SE). It has been found that the quality of AlN can be controlled by adjusting the AlN film thickness. The phenomenon, in which the thicker AlNn film exhibits lower dislocations than the thinner one, demonstrates that thick AlN epitaxial samples can work as a strain relief layer and, in the meantime, help significantly bend the dislocations and decrease total dislocation density with the thicker epi-film. The Urbach's binding energy and optical bandgap (Eg) derived by optical transmission (OT) and SE depend on crystallite size, crystalline alignment, and film thickness, which are in good agreement with XRD and SEM results. It is concluded that under the treatment of thickening film, the essence of crystal quality is improved. The bandgap energies of AlN samples obtained from SE possess larger values and higher accuracy than those extracted from OT. The Bose-Einstein relation is used to demonstrate the bandgap variation with temperature, and it is indicated that the thermal stability of bandgap energy can be improved with an increase in film thickness. It is revealed that when the thickness increases to micrometer order, the thickness has little effect on the change of Eg with temperature.

Recent advances in lipid nanovesicles for targeted treatment of spinal cord injury.

The effective regeneration and functional restoration of damaged spinal cord tissue have been a long-standing concern in regenerative medicine. Treatment of spinal cord injury (SCI) is challenging due to the obstruction of the blood-spinal cord barrier (BSCB), the lack of targeting of drugs, and the complex pathophysiology of injury sites. Lipid nanovesicles, including cell-derived nanovesicles and synthetic lipid nanovesicles, are highly biocompatible and can penetrate BSCB, and are therefore effective delivery systems for targeted treatment of SCI. We summarize the progress of lipid nanovesicles for the targeted treatment of SCI, discuss their advantages and challenges, and provide a perspective on the application of lipid nanovesicles for SCI treatment. Although most of the lipid nanovesicle-based therapy of SCI is still in preclinical studies, this low immunogenicity, low toxicity, and highly engineerable nanovesicles will hold great promise for future spinal cord injury treatments.

A Nucleus-Targeting WT1 Antagonistic Peptide Encapsulated in Polymeric Nanomicelles Combats Refractory Chronic Myeloid Leukemia.

Chronic myeloid leukemia (CML) is recognized as a classic clonal myeloproliferative disorder. Given the limited treatment options for CML patients in the accelerated phase (AP) and blast phase (BP), there is an evident need to develop new therapeutic strategies. This has the potential to improve outcomes for individuals in the advanced stages of CML. A promising therapeutic target is Wilms' tumor 1 (WT1), which is highly expressed in BP-CML cells and plays a crucial role in CML progression. In this study, a chemically synthesized nucleus-targeting WT1 antagonistic peptide termed WIP2W was identified. The therapeutic implications of both the peptide and its micellar formulation, M-WIP2W, were evaluated in WT1+ BP-CML cell lines and in mice. The findings indicate that WIP2W can bind specifically to the WT1 protein, inducing cell cycle arrest and notable cytotoxicity in WT1+ BP-CML cells. Moreover, subcutaneous injections of M-WIP2W were observed to significantly enhance intra-tumoral accumulation and to effectively inhibit tumor growth. Thus, WIP2W stands out as a potent and selective WT1 inhibitor, and the M-WIP2W nanoformulation appears promising for the therapeutic treatment of refractory CML as well as other WT1-overexpressing malignant cancers.

Single-molecule visualization determines conformational substate ensembles in ß-sheet-rich peptide fibrils.

An understanding of protein conformational ensembles is essential for revealing the underlying mechanisms of interpeptide recognition and association. However, experimentally resolving multiple simultaneously existing conformational substates remains challenging. Here, we report the use of scanning tunneling microscopy (STM) to analyze the conformational substate ensembles of ß sheet peptides with a submolecular resolution (in-plane <2.6 Å). We observed ensembles of more than 10 conformational substates (with free energy fluctuations between several kBTs) in peptide homoassemblies of keratin (KRT) and amyloidal peptides (-5Aß42 and TDP-43 341-357). Furthermore, STM reveals a change in the conformational ensemble of peptide mutants, which is correlated with the macroscopic properties of peptide assemblies. Our results demonstrate that the STM-based single-molecule imaging can capture a thorough picture of the conformational substates with which to build an energetic landscape of interconformational interactions and can rapidly screen conformational ensembles, which can complement conventional characterization techniques.

Experimental Insights into Conformational Ensembles of Assembled ß-Sheet Peptides.

Deciphering the conformations and interactions of peptides in their assemblies offers a basis for guiding the rational design of peptide-assembled materials. Here we report the use of scanning tunneling microscopy (STM), a single-molecule imaging method with a submolecular resolution, to distinguish 18 types of coexisting conformational substates of the ß-strand of the 8-37 segment of human islet amyloid polypeptide (hIAPP 8-37). We analyzed the pairwise peptide-peptide interactions in the hIAPP 8-37 assembly and found 82 interconformation interactions within a free energy difference of 3.40 kBT. Besides hIAPP 8-37, this STM method validates the existence of multiple conformations of other ß-sheet peptide assemblies, including mutated hIAPP 8-37 and amyloid-ß 42. Overall, the results reported in this work provide single-molecule experimental insights into the conformational ensemble and interpeptide interactions in the ß-sheet peptide assembly.

Efficacy relevance of PD-L1 expression on circulating tumor cells in metastatic breast cancer patients treated with anti-PD-1 immunotherapy.

PURPOSE: Breast cancer has become the leading cause of cancer mortality in women. Although immune checkpoint inhibitors targeting programmed death-1 (PD-1) are promising, it remains unclear whether PD-L1 expression on circulating tumor cells (CTCs) has predictive and prognostic values in predicting and stratifying metastatic breast cancer (MBC) patients who can benefit from anti-PD-1 immunotherapy. METHODS: Twenty six MBC patients that received anti-PD-1 immunotherapy were enrolled in this study. The peptide-based Pep@MNPs method was used to isolate and enumerate CTCs from 2.0 ml of peripheral venous blood. The expression of PD-L1 on CTCs was evaluated by an established immunoscoring system categorizing into four classes (negative, low, medium, and high). RESULTS: Our data showed that 92.3% (24/26) of patients had CTCs, 83.3% (20/26) of patients had PD-L1-positive CTCs, and 65.4% (17/26) of patients had PD-L1-high CTCs. We revealed that the clinical benefit rate (CBR) of patients with a cut-off value of ≥ 35% PD-L1-high CTCs (66.6%) was higher than the others (29.4%). We indicated that PD-L1 expression on CTCs from MBC patients treated with anti-PD-1 monotherapy was dynamic. We demonstrated that MBC patients with a cut-off value of ≥ 35% PD-L1-high CTCs had longer PFS (P = 0.033) and OS (P = 0.00058) compared with patients with a cut-off value of < 35% PD-L1-high CTCs. CONCLUSION: Our findings suggested that PD-L1 expression on CTCs could predict the therapeutic response and clinical outcomes, providing a valuable predictive and prognostic biomarker for patients treated with anti-PD-1 immunotherapy.

Direct Synthesis of Vertical Self-Assembly Oriented Hexagonal Boron Nitride on Gallium Nitride and Ultrahigh Photoresponse Ultraviolet Photodetectors.

The applications of three-dimensional materials combined with two-dimensional materials are attractive for constructing high-performance electronic and photoelectronic devices because of their remarkable electronic and optical properties. However, traditional preparation methods usually involve mechanical transfer, which has a complicated process and cannot avoid contamination. In this work, chemical vapor deposition was proposed to vertically synthesize self-assembly oriented hexagonal boron nitride on gallium nitride directly. The material composition, crystalline quality and orientation were investigated using multiple characterization methods. Thermal conductivity was found to be enhanced twofold in the h-BN incorporated sample by using the optothermal Raman technique. A vertical-ordered (VO)h-BN/GaN heterojunction photodetector was produced based on the synthesis. The photodetector exhibited a high ultraviolet photoresponsivity of up to 1970.7 mA/W, and detectivity up to 2.6 × 1013 Jones, and was stable in harsh high temperature conditions. Our work provides a new synthesis method to prepare h-BN on GaN-based materials directly, and a novel vertically oriented structure of VO-h-BN/GaN heterojunction, which has great application potential in optoelectronic devices.

Footprints: Stamping hallmarks of lung cancer with patient-derived models, from molecular mechanisms to clinical translation.

The conventional two-dimensional (2D) tumor cell lines in Petri dishes have played an important role in revealing the molecular biological mechanism of lung cancer. However, they cannot adequately recapitulate the complex biological systems and clinical outcomes of lung cancer. The three-dimensional (3D) cell culture enables the possible 3D cell interactions and the complex 3D systems with co-culture of different cells mimicking the tumor microenvironments (TME). In this regard, patient-derived models, mainly patient-derived tumor xenograft (PDX) and patient-derived organoids discussed hereby, are with higher biological fidelity of lung cancer, and regarded as more faithful preclinical models. The significant Hallmarks of Cancer is believed to be the most comprehensive coverage of current research on tumor biological characteristics. Therefore, this review aims to present and discuss the application of different patient-derived lung cancer models from molecular mechanisms to clinical translation with regards to the dimensions of different hallmarks, and to look to the prospects of these patient-derived lung cancer models.

Structural, Surface and Optical Studies of m- and c-Face AlN Crystals Grown by Physical Vapor Transport Method.

Bulk aluminum nitride (AlN) crystals with different polarities were grown by physical vapor transport (PVT). The structural, surface, and optical properties of m-plane and c-plane AlN crystals were comparatively studied by using high-resolution X-ray diffraction (HR-XRD), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. Temperature-dependent Raman measurements showed that the Raman shift and the full width at half maximum (FWHM) of the E2 (high) phonon mode of the m-plane AlN crystal were larger than those of the c-plane AlN crystal, which would be correlated with the residual stress and defects in the AlN samples, respectively. Moreover, the phonon lifetime of the Raman-active modes largely decayed and its line width gradually broadened with the increase in temperature. The phonon lifetime of the Raman TO-phonon mode was changed less than that of the LO-phonon mode with temperature in the two crystals. It should be noted that the influence of inhomogeneous impurity phonon scattering on the phonon lifetime and the contribution to the Raman shift came from thermal expansion at a higher temperature. In addition, the trend of stress with increasing 1000/temperature was similar for the two AlN samples. As the temperature increased from 80 K to ~870 K, there was a temperature at which the biaxial stress of the samples transformed from compressive to tensile stress, while their certain temperature was different.

Nanostructures and Nanotechnologies for the Detection of Extracellular Vesicle.

Liquid biopsy has been taken as a minimally invasive examination and a promising surrogate to the clinically applied tissue-based test for the diagnosis and molecular analysis of cancer. Extracellular vesicles (EVs) carry complex molecular information from the tumor, allowing for the multicomponent analysis of cancer and would be beneficial to personalized medicine. In this review, the advanced nanomaterials and nanotechniques for the detection and molecular profiling of EVs, highlight the advantages of nanotechnology in the high-purity isolation and the high-sensitive and high-specific identification of EVs, are summarized. An outlook on the clinical application of nanotechnology-based liquid biopsy in the diagnosis, prognostication, and surveillance of cancer is also provided. It provides information for developing liquid biopsy based on EVs by discussing the advantages and challenges of functionalized nanomaterials and various nanotechnologies.

m6 A Reader YTHDF1-Targeting Engineered Small Extracellular Vesicles for Gastric Cancer Therapy via Epigenetic and Immune Regulation.

N6 -methyladenosine (m6 A) modulators decide the fate of m6 A-modified transcripts and drive cancer development. RNA interference targeting m6 A modulators promise to be an emerging cancer therapy but is challenging due to its poor tumor targeting and high systematic toxicity. Here engineered small extracellular vesicles (sEVs) with high CD47 expression and cyclic arginine-glycine-aspartic (c(RGDyC)) modification are developed for effective delivery of short interfering RNA against m6 A reader YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) to treat gastric cancer via epigenetic and immune regulation. This nanosystem efficiently depletes YTHDF1 expression and suppresses gastric cancer progression and metastasis through hampering frizzled7 translation and inactivating Wnt/ß-catenin pathway in an m6 A dependent manner. Loss of YTHDF1 mediates overexpression of interferon (IFN)-γ receptor 1 and enhances IFN-γ response, promoting expression of major histocompatibility complex class I on tumor cells to achieve self-presentation of the immunogenic tumor cells to stimulate strong cytotoxic T lymphocytes responses. CD47 expression on the engineered sEVs can competitively bind with signal regulatory protein α to enhance phagocytosis of the tumor cells by tumor-associated macrophages. This versatile nanoplatform provides an efficient and low toxic strategy to inhibit epigenetic regulators and holds great potential in promoting immunotherapy.

A hepatocyte-targeting nanoparticle for enhanced hepatobiliary magnetic resonance imaging.

Hepatobiliary magnetic resonance imaging (MRI) can inform the diagnosis of liver tumours in patients with liver cirrhosis and hepatitis. However, its clinical utility has been hampered by the lack of sensitive and specific contrast agents, partly because hepatocyte-specific nanoparticles, regardless of their surface ligands, are readily sequestered by Kupffer cells. Here we show, in rabbits, pigs and macaques, that the performance of hepatobiliary MRI can be enhanced by an ultrasmall nanoparticle composed of a manganese ferrite core (3 nm in diameter) and poly(ethylene glycol)-ethoxy-benzyl surface ligands binding to hepatocyte-specific transmembrane metal and anion transporters. The nanoparticle facilitated faster, more sensitive and higher-resolution hepatobiliary MRI than the clinically used contrast agent gadoxetate disodium, a substantial enhancement in the detection rate (92% versus 48%) of early-stage liver tumours in rabbits, and a more accurate assessment of biliary obstruction in macaques. The nanoparticle's performance and biocompatibility support the further translational development of liver-specific MRI contrast agents.

Enhanced photodynamic therapy through multienzyme-like MOF for cancer treatment.

Overcoming resistance to apoptosis is a major challenge in cancer therapy. Recent research has shown that manipulating mitochondria, the organelles critical for energy metabolism in tumor cells, can increase the effectiveness of photodynamic therapy and trigger apoptosis in tumor cells. However, there is currently insufficient research and effective methods to exploit mitochondrial damage to induce apoptosis in tumor cells and improve the effectiveness of photodynamic therapy. In this study, we present a novel nanomedicine delivery and therapeutic system called PyroFPSH, which utilizes a nanozymes-modified metal-organic framework as a carrier. PyroFPSH exhibits remarkable multienzyme-like activities, including glutathione peroxidase (GPx) and catalase (CAT) mimicry, allowing it to overcome apoptosis resistance, reduce endogenous glutathione levels, and continuously generate reactive oxygen species (ROS). In addition, PyroFPSH can serve as a carrier for the targeted delivery of sulfasalazine, a drug that can induce mitochondrial depolarization in tumor cells, thereby reducing oxygen consumption and energy supply in the mitochondria of tumor cells and weakening resistance to other synergistic treatment approaches. Our experimental results highlight the potential of PyroFPSH as a versatile nanoplatform in cancer treatment. This study expands the biomedical applications of nanomaterials as platforms and enables the integration of various novel therapeutic strategies to synergistically improve tumor therapy. It deepens our understanding of multienzyme-mimicking active nanocarriers and mitochondrial damage through photodynamic therapy. Future research can further explore the potential of PyroFPSH in clinical cancer treatment and improve its drug loading capacity, biocompatibility and targeting specificity. In summary, PyroFPSH represents a promising therapeutic approach that can provide new insights and possibilities for cancer treatment.

Study of Defects and Nano-patterned Substrate Regulation Mechanism in AlN Epilayers.

The high crystal quality and low dislocation densities of aluminum nitride (AlN) grown on flat and nano-patterned sapphire substrate that are synthesized by the metal-organic chemical vapor deposition (MOCVD) method are essential for the realization of high-efficiency deep ultraviolet light-emitting diodes. The micro-strains of 0.18 × 10-3 cm-2 for flat substrate AlN and 0.11 × 10-3 cm-2 for nano-patterned substrate AlN are obtained by X-ray diffractometer (XRD). The screw and edge dislocation densities of samples are determined by XRD and transmission electron microscope (TEM), and the results indicate that the nano-patterned substrates are effective in reducing the threading dislocation density. The mechanism of the variation of the threading dislocation in AlN films grown on flat and nano-patterned substrates is investigated comparatively. The etch pit density (EPD) determined by preferential chemical etching is about 1.04 × 108 cm-2 for AlN grown on a nano-patterned substrate, which is slightly smaller than the results obtained by XRD and TEM investigation. Three types of etch pits with different sizes are all revealed on the AlN surface using the hot KOH etching method.

Nanomicelles co-loading CXCR4 antagonist and doxorubicin combat the refractory acute myeloid leukemia.

Acute myeloid leukemia (AML) is featured with poor prognosis and high mortality, because chemo-resistance, nonspecific distribution and dose-limiting toxicity lead to a high rate of relapse and a very low 5-year survival percentage of less than 25%. CXCR4 is a highly expressed chemokine receptor in multiple types of AML cells and closely associated with the drug resistance and relapse. In this work, we integrate a chemically synthesized CXCR4 antagonistic peptide and doxorubicin using DSPE-mPEG2000 micelles (referred to as M-E5-Dox) that is applied to a very challenging refractory AML mouse model as well as human AML cell lines. Results showed that M-E5-Dox can effectively bind to the CXCR4-expressing AML cells, downregulating the signaling proteins mediated by CXCR4/CXCL12 axis and increasing the cellular uptake of Dox. Importantly, M-E5-Dox remarkably decreases the leukemic cells in the peripheral blood and bone marrow, as well as their infiltration in the spleen and liver of the AML mice, which in turn prolongs the survival significantly. Meanwhile, M-E5-Dox did not increase the cardiotoxicity of Dox. In conclusion, M-E5-Dox harnesses the functions of CXCR4 specific binding and CXCR4 antagonism of the peptide and the tumor cell killing capacity of Dox, which displays significant therapeutic effects and promising translational potentials for the treatment of refractory AML.