AML cell-derived exosomes suppress the activation and cytotoxicity of NK cells in AML via PD-1/PD-L1 pathway.

Exosomes are bilayer lipid bodies and contain a variety of bioactive molecules such as proteins, lipids, and nucleic acids, and so forth. Exosomes derived from solid tumors may play critical roles in tumor development and immune evasion. However, the underlying effects of tumor-derived exosomes on immune function in modulating intercellular crosstalk within the bone marrow niche during acute myeloid leukemia (AML) development and immune evasion remain largely elusive. In this study, we aimed to explore the role of AML-exos in AML immune evasion. First, we isolated tumor-derived exosomes from AML cells (AML-exos) and revealed the presence of programmed cell death ligand-1 (PD-L1) protein in AML-exos. Next, we demonstrated that AML-exos can directly suppress the activation of natural killer (NK) cells and inhibit the cytotoxicity of NK cells, probably through activating the programmed cell death-1 (PD-1)/PD-L1 pathway. Furthermore, the inhibitory effect of AML-exos on NK cells could be alleviated by either PD-L1 inhibitor or antagonist. In summary, we demonstrated that AML-exos possess a PD-L1-dependent tumor-promoting effect which may contribute to immune tolerance in antitumor therapy, but blocking the PD-1/PD-L1 pathway may alleviate the tumor immunosuppression induced by AML-exos. Our findings in this study may offer a new immunotherapy strategy to cure AML.

The developmental characteristics of proactive and reactive aggression in late childhood: The effect of parental control.

Previous research has confirmed that parental control is related to children's aggressive behavior. However, few studies have focused on proactive and reactive aggression to distinguish the different effects of parental psychological and behavioral control. Moreover, additional longitudinal evidence is needed to understand these links. In the current paper, a three-wave longitudinal study was conducted to examine the developmental characteristics of proactive and reactive aggression and the role of parental control in China. A total of 484 4th- and 7th-grade students participated at wave 1 (51.65% in 4th-grade, Mage = 11.66 ± 1.52 years), 465 students (52.04% in 4th-grade) at wave 2, and 447 children (51.90% in 4th-grade) at wave 3. The results showed that: (1) Proactive aggression in late childhood remained stable overall, while reactive aggression displayed a clear upward trend. (2) In proactive aggression, boys and girls had a consistent developmental trend. The initial level of boys was higher than that of girls. In reactive aggression, the growth rate was inversely associated with their initial level and the initial level of boys in 7th-grade was significantly higher than that of girls. (3) Both parental psychological and behavioral control positively predicted students' reactive aggression in 4th- and 7th-grade, whereas only parental behavioral control positively predicted proactive aggression in 7th-grade students, with no gender differences.

CD93 promotes acute myeloid leukemia development and is a potential therapeutic target.

CD93 is a transmembrane receptor belonging to the Group XIV C-Type lectin family. It is expressed in a variety of cellular types such as monocytes, neutrophils, platelets, microglia, and endothelial cells. CD93 has been reported to play important roles in cell proliferation, cell migration, and tumor angiogenesis. Here, we show CD93 is highly expressed in M4 and M5 subtypes of acute myeloid leukemia (AML) patients, and highly expressed in leukemia stem cells, AML progenitor cells, as well as more differentiated AML cells. We found that CD93 promotes AML cell proliferation, while CD93 deficient AML cells commit to differentiation. We further show that CD93 exerts its proliferative function through downstream SHP-2/Syk/CREB cascade in AML cells. Moreover, human AML cells treated with CD93 mAb combined with αMFc-NC-DM1 (an IgG Fc specific antibody conjugated to maytansinoid DM1), showed a striking reduction of proliferation. Our study revealed that CD93 is a critical participator of AML development and provides a potential therapeutic cell surface target. (160 words).

School bullying and its risk and protective factors in Chinese early adolescents: A latent transition analysis.

Bullying perpetration and victimization are common and problematic occurrences during adolescence. Typically, bullying incidents involve different bullying roles. However, little is known about the developmental stability and changes in these roles. In the present study, we aimed to assess the stability and changes in bullying roles and examine risk and protective factors associated with bullying involvement. A total of 1711 Chinese early adolescents (47.4% girls, Mage = 11.99) participated in the study at two time points approximately 6 months apart. Three subgroups of bullying were identified: bully-victims, victims, and the uninvolved. In terms of stability and changes, the uninvolved were the most stable over time, while victims and bully-victims tended to become the uninvolved. Bully-victims also tended to become victims. Early adolescents with higher levels of parental psychological control and depression symptoms were more likely to be victims or bully-victims. Higher levels of depression symptoms increased the risk of transitioning from being the uninvolved or bully-victims to becoming victims. Higher levels of friendship quality were associated with higher odds of being the uninvolved or transitioning from being victims or bully-victims to becoming the uninvolved. Our findings indicate that bullying roles were relatively stable, with some changes over time. The results also highlight the important function that parental psychological control, friendship quality, and depression symptoms can play in preventing and intervening in bullying.

Exosomes derived from tendon stem cells promote cell proliferation and migration through the TGF ß signal pathway.

Tendon stem cells (TSCs) are a kind of progenitor cells found in tendon niches, which play a key role in the repair of tendon injuries. Exosomes that mediate cell communication are involved in physiological processes and various diseases, while the effect of exosomes derived from TSCs (TSC-exo) on TSCs is still unclear. The purpose of this study is to explore the effect of TSC-exo on TSCs. Analyzing the characteristics of TSC-exo, we found that the TSC-exo were enriched in a large amount of transforming growth factor ß (TGF ß) by western blotting. We also found that the TGF ß carried by TSC-exo can effectively accelerate the proliferation and migration of TSCs. We further found that TGF ß carried by TSC-exo can activate the TGF ß-Smad2/3 and the ERK1/2 signaling pathway in TSCs. Furthermore, matrix metalloenzyme 2 (MMP2), a downstream molecule of Smad2, is regulated by TGF ß carried by TSC-exo. Collectively, our findings provide molecular insights into TSC-exo and indicate that TSC-exo are a potential strategy for treating tendon injuries.

[Application of Ocular Trauma Score in Mechanical Ocular Injury in Forensic Medicine].

OBJECTIVE: To evaluate the application value for the prognosis of mechanical ocular injury cases using ocular trauma score (OTS). METHODS: Four hundred and eleven cases of mechanical ocular trauma were retrospectively reviewed. Of the 449 eyes, there were 317 closed globe injury and 132 open globe injury. OTS variables included numerical values as initial visual acuity, rupture, endophthalmitis, perforat- ing or penetrating injury, retinal detachment and relative afferent pupillary block. The differences be- tween the distribution of the final visual acuity and the probability of standard final visual acuity were compared to analyze the correlation between OTS category and final visual acuity. The different types of ocular trauma were compared. RESULTS: Compared with the distribution of final visual acuity in standard OTS score, the ratio in OTS-3 category was statistically different in present study, and no differences were found in other categories. Final visual acuity showed a great linear correlation with OTS category (r = 0.71) and total score (r = 0.73). Compared with closed globe injury, open globe injury was generally associated with lower total score and poorer prognosis. Rupture injury had poorer prognosis compared with penetrating injury. CONCLUSION: The use of OTS for the patients with ocular trauma can provide re- liable information for the evaluation of prognosis in forensic medicine.

Forensic discrimination of three common brands of kitchen knives in China by ICP-AES and infrared absorption.

A block of an injury instrument will be left in wounds sometimes, and the suspect instrument can be discriminated by comparison with the block that was left through elemental analysis. In this study, three brands (Shibazi, Zhangxiaoquan, Qiaoxifu) of kitchen knives with forged, chop, and slice application series were analyzed by inductively coupled plasma atomic emission spectroscopy (ICP-AES) and Infrared Absorption to investigate the type, number of elements and the reference range used for comparing. The results show that when regarding one or more element as the discriminative threshold, together with 5% relative standard deviation (RSD) as the reference range, all the samples could be distinguished among different series. Furthermore, within the same series, the discriminative capability could reach up to 88.57% for all samples. In addition, elements with high content, such as Cr, Mn, and C, were useful to discriminate among different series, and trace elements, such as Ni, Si, and Cu, were useful within the same series. However, in practice, it is necessary to evaluate the accuracy of the method by Standard Reference Material (SRM) before an examination is performed.

Dual-targeting of tumor cells and subcellular endoplasmic reticulum via AgPPIX-based Janus nanoparticles for photodynamic/immunotherapy against TNBC.

Triple-negative breast cancer (TNBC) is known for its strong invasiveness, high recurrence rates, and poor prognosis. Heme oxygenase-1 (HO-1) is closely related to tumor invasion, metastasis, recurrence and formation of tumor immunosuppression. The expression of HO-1 is high in TNBC and low in normal tissues. In this study, AgPPIX was synthesized as a heme oxygenase-1 (HO-1) inhibitor and a photosensitizer for TNBC therapy. PDA nanoparticles were synthesized and modified with anti-CD24 and p-toluenesulfonamide (PTSC) on their both sides to obtain PTSC@AgPPIX/PDA@anti-CD24 Janus nanoparticles (PAPC) for AgPPIX-targeted delivery. Anti-CD24 is targeted to CD24 on tumor cells and the PTSC moiety is targeted to endoplasmic reticulum (ER), where HO-1 is located. The results indicated that PAPC Janus nanoparticles exhibited higher cytotoxicity in 4T1 cells than that of the mono-modified nanoparticles. PAPC not only inhibited the expression of HO-1 and VEGF but also reduced TrxR activity significantly. Furthermore, PAPC not only promoted intracellular ROS production under laser irradiation for tumor photodynamic therapy (PDT) but also polarized TAMs from M2-type to M1 for tumor immunotherapy. In vivo experiments confirmed that PAPC could remodel the tumor immune microenvironment and almost completely inhibit the tumor growth in mouse models. Therefore, PAPC Janus nanoparticles are a promising nanoplatform with a dual-targeting capacity for TNBC immune/PDT synergistic therapy.

A short-term follow-up study on the relationship between early adolescent proactive/reactive aggression and sleep quality.

OBJECTIVE/BACKGROUND: Sleep quality is closely related to aggressive behavior. Previous studies rarely focused on the relationship between proactive/reactive aggression and sleep quality through a person-centered approach. METHODS: The Pittsburgh Sleep Quality Index Scale and the Reactive-Proactive Aggression Questionnaire were used to assess 553 elementary and middle school students twice at 6-month intervals to better understand the relationship between proactive/reactive aggression and sleep quality in early adolescence. RESULTS: Findings revealed that (1) Sleep quality was positive longitudinally related to both proactive aggression and reactive aggression; Proactive aggression negatively influenced sleep quality, and reactive aggression did not influence sleep quality longitudinally. (2) The sleep quality of persistent non-aggressors and stopped aggressors was significantly better than that of persistent aggressors and new aggressors. CONCLUSION: In early adolescence, proactive aggression was mutually related to sleep quality. Therefore, future research should focus on the bidirectional association between aggression and sleep quality. In addition, we should improve the sleep quality for different types of aggressors and transformers, especially for new aggressors.

Cobalt Doped in Zn-MOF-5 Nanoparticles to Regulate Tumor Microenvironment for Tumor Chemo/Chemodynamic Therapy.

Metal-organic frameworks are often used as a chemotherapeutic drug carrier due to their diverse metal sites and good acid degradation ability. Herein Co-doped Zn-MOF-5 nanoparticles with a high Co doping rate of 60% were synthesized for chemo-chemodynamic synergistic therapy of tumor. Co ions can mediate chemodynamic therapy through Fenton-like reaction and regulate the tumor microenvironment by consuming the reduced glutathione. The CoZn-MOF-5 shows high drug loading capacity with doxorubicin loading rate of 72.8%. The CoZn-MOF-5@PEG@DOX nanodrugs has a strong killing effect on 4T1 cancer cells, suggesting the chemo-chemodynamic synergistic effect on tumor therapy.

Biomimetic Cucurbitacin B-Polydopamine Nanoparticles for Synergistic Chemo-Photothermal Therapy of Breast Cancer.

Breast cancer is the most common malignant tumor in women. Researchers have found that the combined use of multiple methods to treat tumors is a promising strategy. Here, we have developed a biomimetic nano-platform PDA@MB for tumor targeted photothermal therapy (PTT) combined with chemotherapy. The 4T1 cell membrane loaded with cucurbitacin B (CuB) was used to coat polydopamine (PDA) nanoparticles, which gave PDA@MB nanoparticles the ability to target tumors and escape immune cells from phagocytosis. PDA@MB showed excellent photothermal performance including high photothermal conversion efficiency and photostability, and exhibited outstanding in vitro PTT effect under NIR laser irradiation. The high temperature ruptured the PDA@MB membrane to release CuB, which changed the tumor hypoxic environment, down-regulated the FAK/MMP signaling pathway, and significantly inhibited the metastasis and proliferation of tumor cells. The results of in vivo experiments indicated that the tumor growth of the 4T1 mouse tumor model was significantly inhibited. Additionally, toxicity studies showed that PDA@MB had good biocompatibility and safety. In conclusion, this study provides a promising chemo-photothermal therapy (CPT) nano-platform for precise and effective breast cancer therapy.

The role of family and peer factors in the development of early adolescent depressive symptoms: A latent class growth analysis.

Few studies have explored the trajectories of Chinese early adolescent depressive symptoms or comprehensively considered the factors of family and peers. The present study aimed to identify the trajectories of depressive symptoms in early adolescence using a school-based sample assessed in three waves. The study also examined whether family and peer factors were significant predictors. A total of 586 Chinese primary and middle school students participated in the survey. A growth mixture model was used to find the trajectories of depressive symptoms, and multinominal logistic regression was used to identify the predictors. Three trajectories were identified, including a stable-low class, an increasing class, and a high-decreasing class. Results indicated that gender, parental psychological aggression and neglect, parental psychological control, traditional bullying/cyberbullying victimization, and friendship quality were significant predictors. However, witnessing intimate partner violence, parental behavior control, and traditional bullying/cyberbullying perpetration could not significantly predict the trajectories. The findings of this study can provide an empirical basis for teachers and clinical interveners to determine different development trajectories of depressive symptoms and carry out prevention and intervention.

Dual-Responsive multifunctional "core-shell" magnetic nanoparticles promoting Fenton reaction for tumor ferroptosis therapy.

Ferroptosis is a newly found promising cell death pathway, which bypasses apoptosis and overcomes multidrug resistance of tumor. In this study, acid and redox dual-responsive multifunctional magnetic nanoparticles loading with Sorafenib (Sor), namely FMMHG/Sor, were prepared for tumor ferroptosis therapy. Fe3O4 nanoparticles as the core provided sufficient iron ion for ferroptosis and magnetic targeting. Mesoporous organosilica nanoparticles (MON) was coated on the outside of Fe3O4 to form "core-shell" structure, which contained the disulfidebond with redox-responsive. MnO2 was dropped on the surface of MON as gatekeeper, which was decomposed at low pH into O2 to promote drug release. Glucose oxidase (GOD) catalyzed glucose to produce H2O2, which reacted with iron ion to generate hydroxylradical (OH•) vie Fenton reaction. OH• inhibited GPX4 expression to induce ferroptosis with Sor as a synergistic inducer. Hyaluronic acid (HA) protected nanoparticles from removed by immune system and actively targeted to tumor cells. Overall, pH and redox dual-responsive FMMHG/Sor is a promising antitumor nanomedicine with magnetic targeting and active targeting for efficient tumor ferroptosis therapy.

Multifunctional "ball-rod" Janus nanoparticles boosting Fenton reaction for ferroptosis therapy of non-small cell lung cancer.

Ferroptosis is a newly found cell death mechanism, which could bypass apoptosis and reverse multidrug resistance of tumors. However, efficient induction of tumor ferroptosis remains a challenge. In this study, multifunctional "ball-rod" Janus nanoparticles (FTG/L&SMD) were constructed for non-small cell lung cancer (NSCLC) ferroptosis treatment. Protected by tannic acid (TA), FTG/L&SMD maintains long-term function in blood circulation, while modification by 2, 3-dimethylmaleic anhydride (DMMA) confers the FTG/L&SMD with pH-responsive charge reversal. Glucose oxidase (GOD) on FTG/L&SMD catalyzes glucose to produce H2O2. Then, iron ion converts H2O2 to highly active hydroxyl radicals (OH•) via Fenton reaction, leading to lethal lipid peroxidation (LPO) accumulation. Meanwhile, TA reduces Fe3+ to Fe2+ to boost Fenton reaction cycle. Sor down-regulated glutathione peroxidase 4 (GPX4) expression in another pathway to induce ferroptosis synergistically. In vitro studies have shown that compared with sorafenib (Sor), FTG/L&SMD not only has more efficient tumor targeting and higher cytotoxicity, but also inhibits tumor migration. In vivo antitumor therapy experiments demonstrate that FTG/L&SMD inhibits tumor growth efficiently, and its toxicity is negligible. In general, FTG/L&SMD can initiate Fenton reaction cycle and reinforced ferroptosis to kill tumor cells, which is a promising anti-tumor nano-drug for NSCLC.

Effect of ROS generation on highly dispersed 4-layer O-Ti7O13 nanosheets toward tumor synergistic therapy.

Ultra-thin two-dimensional nanosheets have attracted increasing attention due to their great application prospects in nanomaterial science and biomedicine. Herein, we report the preparation of exfoliated raw and oxidized 4-layer Ti7O13 (O-Ti7O13) and their ability to produce reactive oxygen species (ROS). The results show that O-Ti7O13 nanosheets can effectively produce ROS induced by X-ray irradiation. The 4-layer nanosheets can quickly load doxorubicin (DOX) within 5 min with a high loading rate to obtain a novel nanodrug system through their electrostatic adsorption capacity, and they exhibit a sustained release behavior. In this way, chemotherapy, radiation therapy and photodynamic therapy effectively combine for cancer synergistic treatment. We evaluated the cytotoxicity, cellular uptake and intracellular location of the O-Ti7O13 nanosheet-based drug delivery system in A549 lung cancer cells. Our results show that the O-Ti7O13/DOX complex is more cytotoxic to A549 cells than free DOX since a low concentration of loaded DOX (10 µg/mL) with a low dose of X-rays can cause the complete apoptosis of tumor cells. This work reveals that the therapeutic effect of DOX-loaded O-Ti7O13 nanosheets is strongly dependent on their loading mode, and the effects of chemotherapy and photodynamic therapy are enhanced under X-ray irradiation, which allows O-Ti7O13 nanosheet use as a photo-activated drug carrier. This work provides a new strategy for preparing 2D metal oxide nanosheets toward biomedical applications.

Cantharidin-loaded biomimetic MOF nanoparticle cascade to enhance the Fenton reaction based on amplified photothermal therapy.

The treatment efficiency of the Fenton reaction is expected to be greatly restricted due to problems such as inefficient delivery of Fenton catalysis, limited H2O2 concentration and uneven tumour tissue. Accurate photothermal therapy (PTT) could improve the efficiency of Fenton catalysis to some extent by raising the temperature. However, the heat shock response (HSR) of tumour cells caused by PTT and Fenton reaction would attenuate the treatment effect. In this study, we developed an iron ions-mediated Fenton reaction combined with a PTT treatment platform based on a metal-organic framework, i.e., PPy-CTD@MIL-100@MPCM nanoparticles (PCMM NPs), and further explored the inhibitory effect of PCMM NPs on the heat shock response (HSR). PCMM NPs could accumulate in tumour tissue via the coated macrophage cell membranes (MPCMs) to target inflammatory tissues. The photothermal effect of polypyrrole (PPy) accelerated the release of cantharidin (CTD) and iron ions loaded in the PCMM NPs. CTD, as an HSR inhibitor, could inhibit this response of tumour cells and improve the effect of PTT. Meanwhile, the heat generated during the PTT process could improve the efficiency of the Fenton reaction. This study suggested that PCMM NPs could serve as a combined treatment platform to enhance the Fenton reaction based on amplified photothermal therapy.

Anti-CD19 mAb modified mesoporous titanium dioxide as exclusively targeting vector for efficient B-lymphoblastic leukemia therapy.

B lymphoblastic leukemia (B-LL) is a clonal hematopoietic stem cell neoplasm derived from B-cell progenitors, which mainly occurs in children and adolescents and is one of the main causes of death from malignant tumors in this population. The surface marker CD19 is specifically expressed on the membrane of most malignant B-cells, which is widely used as a marker of B-LL antigen-specific immunotherapy. In this study, mesoporous titanium dioxide nanoparticles (MTNs)-based antibody drug delivery system was designed for B-LL treatment. Anti-CD19 monoclonal antibody was conjugated to PEGylated MTNs, and doxorubicin (DOX) was loaded in the nanoparticle. The CD19-PEG-MTN/DOX nanoparticle could recognize CD19+B-LL cell lines and induced them apoptosis, but nontoxic for the normal cells. Further, after treated with CD19-PEG-MTN/DOX nanoparticle, pro-apoptotic proteins Bax and Caspase-3 in KOPN 8 and NALM-6 cells were significantly upregulated, but anti-apoptotic proteins Bcl2, MCL-1, HSP 70, and BAG 3 were downregulated, which indicated the activation of the apoptosis pathway by the nanodrug. By contrast, CD19-PEG-MTN/DOX didn't play a part on CD19-cell line U937. Besides, the cytotoxicity of CD19-PEG-MTN/DOX was low with good biocompatibility. Collectively, CD19-PEG-MTN/DOX is a promising antitumor nanodrug for the treatment of B-LL.

Synergistic multiple active species driven fast estrone oxidation by δ-MnO2 in the existence of methanol.

Endocrine-disrupting chemicals (EDCs) cause serious threats to human health. Five types of MnO2 were synthesized and characterized. They exhibited different removal performances for three EDCs, i.e., estrone (E1), ethynylestradiol (EE2) and bisphenol A (BPA). Only δ-MnO2 can completely remove E1 within 120 min at pH 3.0. Free Mn (III) was determined at the beginning of the reaction and participated in the EDCs removal process. Electron spin resonance (ESR) indicated that δ-MnO2 could produce superoxide anions (·O2-) and singlet oxygen (1O2) in the existence of methanol. The reactive oxygen species (ROS) quenching experiments showed 1O2 have certain contribution to the E1 removal by δ-MnO2. The source of ROS is mainly the lattice oxygen from δ-MnO2, and can be replenished through the layer structure destruction caused by the reaction between Mn(III) and E1. The ROS dependent EDCs removal by δ-MnO2 leads to a deep understanding on this well-known oxidant.

Functionalized PDA/DEX-PEI@HA nanoparticles combined with sleeping-beauty transposons for multistage targeted delivery of CRISPR/Cas9 gene.

CRISPR/Cas9 system has been used as the most powerful gene editing tool for precision medicine and advanced gene therapy. However, its wide applications are limited by the poor biosafety of lentivirus delivery vectors though with high-efficiency transduction. To construct a safer vector and promote genome integration, the CRISPR/Cas9 gene is cloned into a plasmid-based non-viral safe vector Sleeping-Beauty (SB) transposon in this study to obtain pT2SpCas9. Meanwhile, PDA/DEX-PEI@HA (PDPH) nanoparticles are constructed to facilitate the precise CRISPR/Cas9 targeting delivery, by using polydopamine (PDA) as the carrier, hyaluronic acid (HA) as the cell-targeting ligand and dexamethasone (DEX) as the nuclear localization signal (NLS). The results showed that PDPH could deliver pDNA efficiently into the cell and further into the nucleus. The transfection efficiency of PDPH is much higher than that of NPs without HA and DEX. Remarkably, the cytotoxicity of PDPH is negligible in comparison to PEI25k and PEI10k. Western blots showed that after the transfection of PDPH/pT2SpCas9-Nanog/SB11, Nanog protein in HeLa cells is knocked out, and the proliferation and migration abilities of tumor cells are significantly decreased. This study demonstrates that PDA/DEX-PEI25k@HA/pT2SpCas9 (PDPH25 K/pT2SpCas9) has the great potential as a non-viral gene vector for CRISPR/Cas9 delivery and clinical medication.

PEGylated DOX-coated nano graphene oxide as pH-responsive multifunctional nanocarrier for targeted drug delivery.

Nano graphene oxide (NGO) has high drug-loading capacity due to its huge surface area. However, the limited stability and the poor biocompatibility of NGO hampered its application as drug delivery carrier under physiological conditions. Thereby, a new strategy of using chemical conjugation on NGO with hydrophilic polymers was adopted but currently was too complicated, low yield and costly. In this study, doxorubicin-hyd-PEG-folic acid (DOX-hyd-PEG-FA) polymers were coated on the surface of NGO via π-π stocking and the hydrophobic effect between DOX and NGO. With the PEG shell protection, the biocompatibility of NGO was significantly improved. The drug-loading capacity of nanoparticles was more than 100%. FA ligands on the nanoparticle could guide the nanoparticles actively targeting to tumour cells. The hydrazone bond between DOX and PEG was decomposed spontaneously in the weakly acidic environment, which made PEG layer dissociated from NGO. Furthermore, DOX was easily protonized at low pH conditions, which weakened the interaction between DOX and NGO. Thus, DOX could be released rapidly from the nanoparticles in tumour cells. In summary, NGO@DOX-hyd-PEG-FA is an easy-prepared nanoparticle with excellent biocompatibility, high pH-sensitivity and active tumour targeting. Therefore, it is a promising multifunctional nanocarrier effective for targeted drug delivery.