Engineering a targeted and safe bone anabolic gene therapy to treat osteoporosis in alveolar bone loss.

Alveolar bone loss in elderly populations is highly prevalent and increases the risk of tooth loss, gum disease susceptibility, and facial deformity. Unfortunately, there are very limited treatment options available. Here, we developed a bone-targeted gene therapy that reverses alveolar bone loss in patients with osteoporosis by targeting the adaptor protein Schnurri-3 (SHN3). SHN3 is a promising therapeutic target for alveolar bone regeneration, because SHN3 expression is elevated in the mandible tissues of humans and mice with osteoporosis while deletion of SHN3 in mice greatly increases alveolar bone and tooth dentin mass. We used a bone-targeted recombinant adeno-associated virus (rAAV) carrying an artificial microRNA (miRNA) that silences SHN3 expression to restore alveolar bone loss in mouse models of both postmenopausal and senile osteoporosis by enhancing WNT signaling and osteoblast function. In addition, rAAV-mediated silencing of SHN3 enhanced bone formation and collagen production of human skeletal organoids in xenograft mice. Finally, rAAV expression in the mandible was tightly controlled via liver- and heart-specific miRNA-mediated repression or via a vibration-inducible mechanism. Collectively, our results demonstrate that AAV-based bone anabolic gene therapy is a promising strategy to treat alveolar bone loss in osteoporosis.

Tumor Microenvironment-Triggered Self-Adaptive Polymeric Photosensitizers for Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT) employs photosensitizers to convert nearby oxygen into toxic singlet oxygen (1O2) upon laser light irradiation, showing great potential as a noninvasive approach for tumor ablation. However, the therapeutic efficacy of PDT is essentially impeded by π-π stacking and the aggregation of photosensitizers. Herein, we propose a tumor microenvironment-triggered self-adaptive nanoplatform to weaken the aggregation of photosensitizers by selenium-based oxidation at the tumor site. The selenide units in a selenium-based porphyrin-containing amphiphilic copolymer (PSe) could be oxidized into hydrophilic selenoxide units, leading to the nanoplatform self-expansion and stretching of the distance between intramolecular porphyrin units. This process could provide a better switch to greatly reduce the aggregation of photosensitive porphyrin units, generating more 1O2 upon laser irradiation. As verified in a series of in vitro and in vivo studies, PSe could be efficiently self-adapted at tumor sites, thus significantly enhancing the PDT therapeutic effect against solid tumors and minimizing side effects.

Fabrication of a MXene-based shape-memory hydrogel and its application in the wound repair of skin.

Wound dressings can generally complete hemostasis and provide temporary protection after skin damage. Herein, a MXene-based hydrogel was prepared from MXene, gelatin, poly(ethylene glycol)diacrylate (PEGDA) and N,N'-methylenebis(acrylamide) (HEAA) to prepare wound-dressing hydrogels for skin repair. HEAA and PEGDA crosslink polymerization formed the first layer of the network. Hydrogen bonds between MXene, PHEAA, and gelatin formed the second layer of the network. To make the hydrogel more suitable for skin repair, the mechanical properties of the hybrid hydrogel were adjusted. The MXene-based hydrogel could recover its original shape in 16 s upon immersion in water or for a few minutes under light irradiation. The obtained hydrogel showed good photothermal properties upon light irradiation (808 nm, 1 W cm-2) for 20 s, and its temperature on the surface could reach 86.4 °C. Due to its good photothermal properties, this MXene-based hydrogel was suitable for skin repair.

Designing highly stable ferrous selenide-black phosphorus nanosheets heteronanostructure via P-Se bond for MRI-guided photothermal therapy.

BACKGROUND: The design of stable and biocompatible black phosphorus-based theranostic agents with high photothermal conversion efficiency and clear mechanism to realize MRI-guided precision photothermal therapy (PTT) is imminent. RESULTS: Herein, black phosphorus nanosheets (BPs) covalently with mono-dispersed and superparamagnetic ferrous selenide (FeSe2) to construct heteronanostructure nanoparticles modified with methoxy poly (Ethylene Glycol) (mPEG-NH2) to obtain good water solubility for MRI-guided photothermal tumor therapy is successfully designed. The mechanism reveals that the enhanced photothermal conversion achieved by BPs-FeSe2-PEG heteronanostructure is attributed to the effective separation of photoinduced carriers. Besides, through the formation of the P-Se bond, the oxidation degree of FeSe2 is weakened. The lone pair electrons on the surface of BPs are occupied, which reduces the exposure of lone pair electrons in air, leading to excellent stability of BPs-FeSe2-PEG. Furthermore, the BPs-FeSe2-PEG heteronanostructure could realize enhanced T2-weighted imaging due to the aggregation of FeSe2 on BPs and the formation of hydrogen bonds, thus providing accurate PTT guidance and generating hyperthermia to inhabit tumor growth under NIR laser with negligible toxicity in vivo. CONCLUSIONS: Collectively, this work offers an opportunity for fabricating BPs-based heteronanostructure nanomaterials that could simultaneously enhance photothermal conversion efficiency and photostability to realize MRI-guided cancer therapy.

Axial-Circular Magnetic Levitation: A Three-Dimensional Density Measurement and Manipulation Approach.

Magnetic levitation (MagLev) is a promising technology for density-based analysis and manipulation of diamagnetic objects of various physical forms. However, one major drawback is that MagLev can be performed only along the central axis (one-dimensional MagLev), thereby leading to (i) no knowledge about the magnetic field in regions other than the axial region, (ii) inability to handle objects of similar densities, because they are aggregated in the axial region, and (iii) objects that can be manipulated (e.g., separated or assembled) in only one single direction, that is, the axial direction. This work explores a novel approach called "axial-circular MagLev" to expand the operational space from one dimension to three dimensions, enabling substances to be stably levitated in both the axial and circular regions. Without noticeably sacrificing the total density measurement range, the highest sensitivity of the axial-circular MagLev device can be adjusted up to 1.5 × 104 mm/(g/cm3), approximately 115× better than that of the standard MagLev of two square magnets. Being able to fully utilize the operational space gives this approach greater maneuverability, as the three-dimensional self-assembly of controllable ring-shaped structures is demonstrated. Full space utilization extends the applicability of MagLev to bioengineering, pharmaceuticals, and advanced manufacturing.

Golgi membrane protein GP73 modified-liposome mediates the antitumor effect of survivin promoter-driven HSVtk in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide, and there is currently no effective therapeutic strategy in clinical practice. Gene therapy has great potential for decreasing tumor-induced mortality but has been clinically limited because of the lack of tumor-specific targets and insufficient gene transfer. The study of targeted transport of therapeutic genes in HCC treatment seems to be very important. In this study, we evaluated a gene therapy approach targeting HCC using the herpes simplex virus thymidine kinase/ganciclovir (HSVtk/GCV) suicide gene system in HCC cell lines and in an in vivo human HCC xenograft mouse model. GP73-modified liposomes targeted gene delivery to the tumor tissue, and the survivin promoter drove HSVtk expression in the HCC cells. Our results showed that the survivin promoter was specifically activated in tumor cells and HSVtk was expressed selectively in tumor cells. Combined with GCV treatment, HSVtk expression resulted in suppression of HCC cell proliferation via enhancing apoptosis. Moreover, tail vein injection of GP73-HSVtk significantly suppressed the growth of xenograft tumors through an apoptosis-dependent pathway and extended the survival of tumor-bearing mice without damaging the mice liver functions. Taken together, this study demonstrates an effective cancer-specific gene therapy strategy using the herpes simplex virus thymidine kinase/ganciclovir (HSVtk/GCV) suicide gene system for HCC that can be further developed for future clinical trials.

A Novel Conductive Polypyrrole-Chitosan Hydrogel Containing Human Endometrial Mesenchymal Stem Cell-Derived Exosomes Facilitated Sustained Release for Cardiac Repair.

Myocardial infarction (MI) results in cardiomyocyte necrosis and conductive system damage, leading to sudden cardiac death and heart failure. Studies have shown that conductive biomaterials can restore cardiac conduction, but cannot facilitate tissue regeneration. This study aims to add regenerative capabilities to the conductive biomaterial by incorporating human endometrial mesenchymal stem cell (hEMSC)-derived exosomes (hEMSC-Exo) into poly-pyrrole-chitosan (PPY-CHI), to yield an injectable hydrogel that can effectively treat MI. In vitro, PPY-CHI/hEMSC-Exo, compared to untreated controls, PPY-CHI, or hEMSC-Exo alone, alleviates H2O2-induced apoptosis and promotes tubule formation, while in vivo, PPY-CHI/hEMSC-Exo improves post-MI cardiac functioning, along with counteracting against ventricular remodeling and fibrosis. All these activities are facilitated via increased epidermal growth factor (EGF)/phosphoinositide 3-kinase (PI3K)/AKT signaling. Furthermore, the conductive properties of PPY-CHI/hEMSC-Exo are able to resynchronize cardiac electrical transmission to alleviate arrythmia. Overall, PPY-CHI/hEMSC-Exo synergistically combines the cardiac regenerative capabilities of hEMSC-Exo with the conductive properties of PPY-CHI to improve cardiac functioning, via promoting angiogenesis and inhibiting apoptosis, as well as resynchronizing electrical conduction, to ultimately enable more effective MI treatment. Therefore, incorporating exosomes into a conductive hydrogel provides dual benefits in terms of maintaining conductivity, along with facilitating long-term exosome release and sustained application of their beneficial effects.

An optimum biomass fractionation strategy into maximum carbohydrates conversion and lignin valorization from poplar.

Appropriate fractionation of lignocellulosic biomass into useable forms is a key challenge to achieving an economic bioethanol production. In the present study, four different fractionation strategies of hydrothermal-, NaOH-, ethanol-, and NaOH catalyzed ethanol pretreatment were investigated to compare their abilities of cellulose conversion. Results showed that NaOH catalyzed ethanol pretreatment showed a rather high extent of delignification of 85.92%, which also enhanced the retention of cellulose (92.56%) and hemicellulose (76.57%); while other pretreatments tended to produce cellulose fraction which was insufficient to achieve the whole component utilization. After simultaneous saccharification and fermentation at high solids loading, synergistic maximization of xylose (42.47 g/L) and ethanol (85.74 g/L) output was achieved via alkaline ethanol pretreatment. Lignin characterization information showed that alkaline ethanol pretreatment facilitates the cleavage of ß-O-4 linkage and further converts into arylglycerol. Moreover, less condensed substructure units with high processing activity were also generated in S- and G- lignin.

[Accuracy evaluation of recording maxillomandibular relation with the mandibular kinesiography].

PURPOSE: To evaluate the accuracy of recording maxillomandibular position relationship with the mandibular kinesiography by surface electromyography analysis of the masticatory muscles and MRI of temporomandibular joint (TMJ). METHODS: Eight edentulous patients were selected randomly, and the maxillomandibular position relationship was determined by mandibular kinesiography and traditional method respectively. Then the corresponding bite plates were made to wear. Surface electromyography test of left and right anterior temporal and masseter muscle and magnetic resonance scan of the temporomandibular joint were performed on closed mouth position to record peak potentials, calculate asymmetric indexes, analyze the position relationship between the joint disc and the condyle, measure TMJ joint space. SPSS 18.0 software package was used for data analysis. RESULTS: There was no significant difference in the amplitude of the anterior temporal or masseter muscle, the asymmetry index of total, asymmetry index of masseter, asymmetry index of temporalis, the anterior, upper and posterior spaces of TMJ between the mandibular kinesiography group and the traditional group (P＞0.05). The temporomandibular articular disc process relationship of the two groups were conformed to the normal physiological position relationship. CONCLUSIONS: Mandibular kinesiography could accurately record the maxillomandibular position relationship in patients with edentulous jaws.

Effects of Y-nodes in DGEBA/TDE-85/MTHPA blends on their thermal and mechanical properties: MD simulation and experimental study.

With the development of alternate electrical power system and the improvement of voltage level, the operation conditions faced by epoxy resin (ER) insulation materials are becoming more and more complex. The traditional ER materials have been difficult to meet the increasingly stringent requirements. In this paper, the thermal and mechanical properties of DGEBA/TDE-85/MTHPA blend system were studied by molecular dynamics (MD) simulation and experiment. The results show that the addition of TDE-85 can significantly improve the thermal and mechanical properties, and the comprehensive improvement effect is the best when the molar ratio of DGEBA and TDE-85 is about 8:2. The experimental results are consistent with the simulation results. Further analysis of the micro-parameters of the monomer and the cross-linking network found that the torsional energy barrier of TDE-85 is higher than DGEBA. And the compatibility of the two ER is better when the ratio is 8:2. In addition, TDE-85 can introduce high-stability Y-nodes into the system, making the cross-linked network more stable, which has a significant effect on improving the thermal and mechanical properties. The research provide a reference for the blending modification of high-performance ER for high-voltage insulation.

[Characterization of Microplastic Leachate from Different Polymers and Its Effect on Seed Germination of Lettuce].

Accumulation of microplastics in soil could interfere with the germination and growth of plants. However, the chemical risks raised by leachate of microplastics remain unknown. Here, we prepared microplastic leachate at different extraction temperatures (25 and 50℃) using microplastic fibers derived from polyamide (PA) and polyethylene (PE) and conducted the seed germination test of microplastic leachates to investigate the toxic effects of microplastic leachates on lettuce (Lactuca sativa L.). Furthermore, characteristics of the microplastic leachate, such as DOC and DON concentrations and parameters of UV-vis, were measured. The results revealed that the concentration of DOC and DON in the leachate of PA was significantly higher than that of PE. DOC and DON concentration in the leachate of PA increased with extraction temperature. Additionally, the aromaticity, hydrophobic component content, and molecular weight of leachates were significantly affected by the polymers of microplastic, whereas the extraction temperature had no effect. Compared to those in CK, the microplastic leachates reduced the indicators such as germination vigor, germination index, and vigor index of lettuce seeds; however, it had no impact on agronomic traits, such as plant height, root length, fresh weight, and dry weight. Meanwhile, some seeds had abnormal developments of radicles and cotyledons under the microplastic leachate treatments. This demonstrates that the substances leached from microplastics could interfere with the germination process of lettuce seeds. Therefore, the chemical risks exerted by the microplastics to the soil and plant system require further attention.

Improving the solubility of melanin nanoparticles from apricot kernels is a potent drug delivery system.

BACKGROUND: Melanin can be used in biomedical nanomaterials, but its solubility in water and bioavailability are low. AIM: Melanin nanoparticles were prepared and then PEG-natural melanin nanoparticles (NMNP-PEG) were obtained with good performance and optimize their (water solubility, dispersion stability, chelating metal ions, photothermal stability, drug delivery, and biocompatibility), therefore improve the water solubility of melanin and broaden its application scope in biology, medicine, food, and other fields. METHODS: MFAK (melanin from apricot kernels) and NMNP-PEG were prepared and characterized using ultraviolet-visible spectrophotometry (UV-Vis), high-performance liquid chromatography (HPLC), Fourier-transform infrared spectroscopy (FTIR), 1H nuclear magnetic resonance (NMR), and electron microscopy. The chelation rate of metal ions, photothermal effect, doxorubicin loading, and cytotoxicity (MCF-7 cells) were examined. RESULTS: UV-Vis, HPLC, FTIR, and NMR indicated that NMNPs contained melanin. NMNPs could be successfully modified using PEG. Under physiological pH conditions (pH 7.4), the metal ion chelation rate of NMNP-PEG increased with time and peaked at 12 h. The photothermal assay showed a temperature enhancement of 26.3°C with 1 mg/mL NMNP-PEG, compared with 1.9℃ with water. The NMNP-PEGs had a typical peak for doxorubicin in the FTIR spectrum, and the peak intensity was proportional to the drug loading. The release of doxorubicin in an acidic buffer was 40.8% at 24 h, almost threefold that in a neutral buffer (11.9%). There was no obvious cytotoxicity from NMNP-PEG. CONCLUSION: NMNP-PEG displays good stability, high metal ion chelation ability, efficient photothermal conversion potential, drug-retaining capability, sustained controlled drug release, and biocompatibility. This study provides a theoretical basis for NMNP-PEG applications in medicine (targeting specific sites to diagnose and treat diseases), food (extending the shelf life of food), and biology (as metal ion chelating agents to remove heavy metals from wastewater).

Chemiexcited Photodynamic Therapy Integrated in Polymeric Nanoparticles Capable of MRI Against Atherosclerosis.

Background: Photodynamic therapy (PDT) has achieved continued success in the treatment of tumors, but its progress in the treatment of atherosclerosis has been limited, mainly due to the low tissue-penetration ability of the excitation light for photosensitizers. Methods: In this study, we designed a chemiexcited system producing singlet oxygen in an attempt to apply PDT for the treatment of atherosclerosis without the irradiation of external light. The system designed was polymeric nanoparticles (NPs) equipped with chemical fuel and photosensitizers, cross-linked with an Fe3+-catechol complex for stabilization and magnetic resonance imaging (MRI). Results: The system (FeCNPs for short) accumulated effectively in plaques, providing persistent and enhanced T 1-weighted contrast ability. FeCNPs also prevented progression of atherosclerosis via macrophage elimination, and obviously reduced plaque size and thickness revealed by T 1-weighted MRI. Expression of CD68, MCP1, and TNFα was significantly reduced after treatment. However, low doses of FeCNPs exhibited better therapeutic efficacy than high doses. Furthermore, low-dose FeCNPs exhibited effective macrophage elimination in aortic arches and abdominal aortae, but inefficiency in the thoracic aorta, aortic hiatus, and aorta-iliac bifurcation. Conclusion: This study provides the first example of a combination of MRI and chemiexcited PDT for atherosclerosis, evidencing the effectiveness of PDT and providing significant pointers for developing nanotherapy on atherosclerosis.

[Study on preparation and tissue distribution of hydroxycamptothecin liposomes].

OBJECTIVE: To develop HCPT liposome with small diameter and to study the tissue distribution of the HCPT liposome in rats. METHOD: Modified solvent-injection method was used to prepare HCPT liposome. The entrapment efficiency, morphology, size and zeta potential were also investigated. The transformation temperature and the ratio of cholesterol to phospholipids were determined by fluorescence spectrophotometry. HCPT liposome and HCPT injection (5 mg x kg(-1)) were injected by tail vein in mice, respectively. The tissue concentrations of HCPT were determined by LC-MS/MS. RESULT: Under selected process conditions, the HCPT liposomes were spherical and integrated with the mean entrapment efficiency of (96.83 +/- 2.32)%, the size of (180.5 +/- 4.5) nm and the zeta potential of--(32.1 +/- 1.3) mV. It showed that the optimum proportion of cholesterol to phospholipids was 1.5: 10, the optimum transformation temperature was 32.5 degrees C; HCPT liposome at a dose of 5 mg x kg(-1) led to higher concentration and longer duration of action compared with HCPT injection on market. CONCLUSION: HCPT liposome prepared by solvent-injection method was characteristic of small mean diameter, high encapsulation efficiency and long circulation in vivo.

Hydrothermal co-hydrolysis of corncob/sugarcane bagasse/Broussonetia papyrifera blends: Kinetics, thermodynamics and fermentation.

Biorefinery of biomass blends can achieve sustainable development of biofuel production. Herein, three lignocellulosic wastes with significant differences in chemical composition-namely corncob (CC), sugarcane bagasse (SB), and Broussonetia papyrifera (BP)-were selected to investigate their hydrothermal co-hydrolysis kinetics and thermodynamics of different biomass blends. Activation energies of hemicellulose decomposition (Ea1, 90.59 kJ/mol) for CC/SB were lower than those for CC (126.12 kJ/mol) and CC/SB/BP (153.62 kJ/mol). BP (having a high content of nitrogen sources) loading weakened the acidic autohydrolysis of CC/SB hemicellulose, but yielded stable products as indicated by the negative entropy value for CC/SB/BP hydrolysis. Cumulative feedback inhibition occurred among different biomass, and it could be minimized by controlling the blending ratio. The highest total xylose yield was 83.64% for CC/SB with a mass ratio of 2:1. Moreover, biomass blend of CC/SB/BP enabled complete utilization of hexose, pentose and amino acids by co-production of ethanol and microalga biomass.

Sodium hydroxide catalytic ethanol pretreatment and surfactant on the enzymatic saccharification of sugarcane bagasse.

The effect of NaOH catalytic ethanol pretreatment under various temperatures (130-180 °C) and time (15-90 min) on the chemical composition and enzymatic saccharification of sugarcane bagasse was investigated in this study. The results showed that NaOH catalytic ethanol pretreatment assisted delignification and the reservation of cellulose and hemicellulose. When sugarcane bagasse was pretreated at 180 °C for 30 min, a substantial glucose yield of 91.6% was obtained after hydrolysis for 72 h, representing 94.6% of glucose in pretreated residue. This yield was promoted with respect to the compositional change and surface alteration of pretreated substrate. With the supplement of Tween 80, the enzyme usage would be saved by 50% and the enzymolysis time could be shortened to 24 h while obtaining comparable glucose yield. This study provided an economical feasible and gradual process for the generation of glucose, which was followed by fermentation and conversion to platform chemicals.

Molecular simulation of nano polyhedral oligomeric silsesquioxane doping effect on the properties of two-component crosslinked epoxy resin.

Epoxy resin (EP) has been extensively used in the field of insulation for its excellent electrical strength, mechanical property, chemical stability, and low cost. In this paper, computer molecular simulation is used to analyze the influence of nano-POSS (Nano-Polyhedral Oligomericsils Esquioxane) doping on the properties of epoxy composite from the micro point of view, which can provide a scientific basis for the optimization of the epoxy system. Two kinds of nano-POSS fillers with different mass fractions were doped into the base material of diglycidyl ether of bisphenol A (DGEBA) and 3,4-epoxycyclohexylmethyl 3,4-epoxycyclohexanecar (OSC). By molecular dynamics (MD) simulation the influence of nanofillers on the microstructure, thermal and mechanical properties of the composite were analyzed. Simulation results show that the doping of nano-POSS can improve the thermal and mechanical properties of the epoxy composite. Different nano-POSS has little effect on the glass transition temperature (Tg), coefficient of thermal expansion (CTE), and mechanical properties of the epoxy system, while the filling amount has an obvious improvement effect. Compared with EP/methyl-POSS system, the thermal and mechanical properties of the EP/phenyl-POSS system are better. At the same time, the doping of nano-POSS changed the microstructure parameters of epoxy composite. With the increase of nano-POSS filler content, fractional free volume (FFV) and mean square displacement (MSD) of both EP/POSS systems increased after the first drop. Besides, when the content of nano-POSS exceeded a certain range, the aggregation of filler itself hindered the accumulation of epoxy molecular chain segments.

Intensification of sugar production by using Tween 80 to enhance metal-salt catalyzed pretreatment and enzymatic hydrolysis of sugarcane bagasse.

In this study, different metal-salt catalyzed pretreatment was presented to disorganize the obstinate structure by eliminating the majority of hemicellulose, fractional of lignin, and improve the enzymatic saccharification of sugarcane bagasse. With the accession of Tween 80 during enzymolysis, all metal-salt pretreated substrates presented higher glucose yields, especially for CuCl2. Furthermore, Tween 80 was added to the pretreatment, enhancing the elimination of hemicellulose and lignin, decreasing the degradation of sugars to inhibitors, and presenting superior performance on improving glucose yield. In addition, the maximum glucose yield of 88.0% was achieved by using Tween 80 concomitantly with AlCl3 pretreatment and enzymolysis. It was also found that adding Tween 80 during pretreatment or/and enzymolysis after 24 h could liberate the similar glucose without Tween 80 after 72 h. However, the enhancement of Tween 80 at 6 h was higher than that at 72 h.

Succession of diazotroph community and functional gene response to inoculating swine manure compost with a lignocellulose-degrading consortium.

Diazotroph community contributes to the nitrogen mass and improves the agronomic quality of composting product, but their responses to microbial inoculation during composting are unclear. In this study, the lignocellulose-degrading consortium was inoculated at different levels (0%: CK (control) and 10%: T) to investigate their effects on the variations in the diazotroph community and functional gene during composting. In the later composting phase, the nifH gene copy number was 17.50-25.28% higher in T than CK. The nitrogenase abundance in CK and T were 0.042% and 0.046% in composting product, respectively. Network analysis indicated that inoculation affected the co-occurrence patterns of the diazotroph community and changed the keystone species composition. Partial least-squares path modeling showed that available carbon sources and the succession of the diazotroph community mainly determined the increased abundance of nifH gene. Microbial inoculation stimulated the diazotrophs activities, and was conducive to the nitrogen production in composting product.

Paclitaxel-loaded magnetic nanocrystals for tumor neovascular-targeted theranostics: an amplifying synergistic therapy combining magnetic hyperthermia with chemotherapy.

A combination of chemotherapy and targeted magnetic hyperthermia (TMH) via a designed magnetic nanocrystal (MNC) drug delivery system was considered as an effective tumor synergistic therapy strategy. In this paper, we successfully synthesized tumor neovascular-targeted Mn-Zn ferrite MNCs, which encapsulated paclitaxel (PTX) in a biocompatible PEG-phospholipid (DSPE-PEG2000) layer and surface, simultaneously coupled with a tripeptide of arginine-glycine-aspartic acid (RGD). The high-performance RGD-modified MNC loaded with PTX (MNCs-PTX@RGD) embodied excellent magnetic properties, including high-contrast magnetic resonance imaging (MRI) and remarkable magnetically induced heat generation ability. We established the mouse model bearing subcutaneous 4T1 breast tumor, and demonstrated that MNCs-PTX@RGD could be effectively located in the tumor neovascular epithelial cells under the guidance of in vivo MRI. Notably, MNCs-PTX@RGD could easily penetrate into the tumor tissue from the tumor-fenestrated vascular networks for capturing a sufficient temperature (around 43 °C) exposed to an alternative current magnetic field (ACMF, 2.58 kA m-1, 390 kHz), leading to an effective TMH effect. Subsequently, the TMH-mediated temperature elevation accelerated the PTX release from the inner lipid layer, promoting the synergetic thermo-chemotherapy in vivo. The amplifying synergistic treatment strategy obviously improved the anti-tumor efficacy of MNCs-PTX@RGD, and simultaneously increased the survival time of the mice to more than 46 days, which provided a broad development prospect in clinical applications.