Lysosome-Targeting Bacterial Outer Membrane Vesicles for Tumor Specific Degradation of PD-L1.

Increased expression of immune check point genes, such as PD-L1, is one of the main reasons for immunosuppression, especially for colon cancer. Development of novel therapeutic strategies is of great importance to improve the prognosis. In this study, outer membrane vesicles (OMV) derived from Gram-negative bacteria are engineered to immune checkpoint blockade nanosystem for efficient elicitation of anti-tumor immunity. Briefly, the OMVs are engineered with Lyp1-Traptavidin (S52G, R53D mutant of streptavidin) fusion protein displayed on the surface. The Lyp-1 endows the OMV with the capacity to target tumor tissues, while the Traptavidin ensures easy decoration of biotinylated anti-PD-L1 and biotinylated M6P (mannose 6-phosphate). The simultaneously anchored anti-PD-L1 and M6P (ligand for cation-independent mannose 6-phosphate receptor) on the engineered OMVs coordinately direct the membrane PD-L1 to lysosome for degradation, and thus unleash the anti-tumor immunity. With syngeneic tumor model, the engineered OMVs are confirmed to boost immunity, inhibit cancer growth, and thus prolong survival. Together, A proposed OMV-based modular nanosystem that enables assembly of biotinylated anti-PD-L1 and M6P on the surface for tumor-targeted immune checkpoint blockade.

Multipotent miRNA Sponge-Loaded Magnetic Nanodroplets with Ultrasound/Magnet-Assisted Delivery for Hepatocellular Carcinoma Therapy.

Gene therapy is likely to be the most promising way to tackle cancer, while defects in molecular strategies and delivery systems have led to an impasse in clinical application. Here, it is found that onco-miRNAs of the miR-515 and -449 families were upregulated in hepatocellular carcinoma (HCC), and the sponge targeting miR-515 family had a significant probability to suppress cancer cell proliferation. Then, we constructed non-toxic sponge-loaded magnetic nanodroplets containing 20% C6F14 (SLMNDs-20%) that are incorporated with fluorinated superparamagnetic iron oxide nanoparticles enhancing external magnetism-assisted targeting and enabling a direct visualization of SLMNDs-20% distribution in vivo via magnetic resonance imaging monitoring. SLMNDs-20% could be vaporized by programmable focused ultrasound (FUS) activation, achieving ∼45% in vitro sponge delivery efficiency and significantly enhancing in vivo sponge delivery without a clear apoptosis. Moreover, the sponge-1-carrying SLMNDs-20% could effectively suppress proliferation of xenograft HCC after FUS exposure because sponge-1-suppressing onco-miR-515 enhanced the expression of anti-oncogenes (P21, CD22, TIMP1, NFKB, and E-cadherin) in cancer cells. The current results indicated that ultrasonic cavitation-inducing sonoporation enhanced the intracellular delivery of sponge-1 using SLMNDs-20% after magnetic-assisted accumulation, which was a therapeutic approach to inhibit HCC progression.

High-Performance Delivery of a CRISPR Interference System via Lipid-Polymer Hybrid Nanoparticles Combined with Ultrasound-Mediated Microbubble Destruction for Tumor-Specific Gene Repression.

The dCas9-based CRISPR interference (CRISPRi) system efficiently silences genes without causing detectable off-target activity, thus showing great potential for the treatment of cancer at the transcriptional level. However, due to the large size of the commonly used CRISPRi system, effective delivery of the system has been a challenge that hinders its application in the clinic. Herein, a combination of pH-responsive lipid-polymer hybrid nanoparticles (PLPNs) and ultrasound-mediated microbubble destruction (UMMD) is used for the delivery of the CRISPRi system. The core-shell structure of PLPNs can effectively be loaded with the CRISPRi plasmid, and increases the time spent in the circulating in vivo, and "actively target" cancer cells. Moreover, the combination of PLPNs with UMMD achieves a higher cellular uptake of the CRISPRi plasmid in vitro and retention in vivo. Furthermore, when PLPNs loaded with a CRISPRi plasmid that targets microRNA-10b (miR-10b) are used in combination with UMMD, it results in the effective repression of miR-10b in breast cancer, simultaneous disturbance of multiple cell migration and invasion-related signaling pathways, and a significant inhibition of lung metastasis. Thus, the established system presents a versatile, highly efficient, and safe strategy for delivery of the CRISPRi system both in vitro and in vivo.

Enhanced Sonothrombolysis Induced by High-Intensity Focused Acoustic Vortex.

High-intensity focused ultrasound (HIFU) thrombolysis provides a targeted and non-invasive therapy for thrombosis-related diseases. Rapid thrombolysis and restoration of blood flow are vital to reduce the disability and death rate. The objective of this study was to explore the feasibility of using a high-intensity focused acoustic vortex (HIFAV) to enhance sonothrombolysis. The in vitro clots were treated with HIFU with a peak negative pressure (PNP) of 2.86 MPa (HIFU A) or 3.27 MPa (HIFU B) or HIFAV with a PNP of 2.14 MPa. The results revealed that HIFAV thrombolysis could achieve a significantly higher efficiency than HIFU (HIFAV: 65.4%, HIFU A: 24.1%, HIFU B: 31.6%, p < 0.01), even at a lower intensity. The average size of the debris particles generated in HIFAV thrombolysis was similar to that in HIFU. Additionally, the cavitation activities were found to be more intense in HIFAV thrombolysis. Although the efficiency of HIFAV thrombolysis was higher when the pulse repetition frequency increased from 100 to 500 Hz (41.4% vs. 65.4%, p < 0.05), it decreased when the PRF reached 1000 Hz (29.9%). Lastly, it was found that increasing the duty cycle from 5% to 15% led to a higher efficiency in HIFAV thrombolysis (40.3% vs. 75.2%, p < 0.001). This study illustrated that HIFAV provided enhanced thrombolysis and that its efficiency could be further increased by optimizing the ultrasound parameters.

Synergistic therapy for orthotopic gliomas via biomimetic nanosonosensitizer-mediated sonodynamic therapy and ferroptosis.

Ferroptosis is an emerging form of programmed cell death, and its combination with sonodynamic therapy (SDT) for anti-tumor activity is gradually attracting attention. However, their application against gliomas has not been studied. Herein, multifunctional cancer homologous targeting biomimetic nanoparticles (PIOC@CM NPs) encapsulating both Fe3O4 and Ce6 were constructed as a nanosonosensitizer. Based on focused ultrasound (US) combined with circulating microbubbles (MBs) to open the blood-brain barrier (BBB) in a safe and transient manner, the development of a therapeutic strategy to integrate the biomimetic nanosonosensitizer-mediated SDT and ferroptosis could achieve synergistic therapeutic effects against gliomas. We demonstrated that the glioma C6 cell membrane (CM) on the surface of the NPs allowed the nanosonosensitizer to accumulate selectively in tumors through homologous targeting in vitro. After efficient internalization in C6 cells, the PIOC@CM NPs could significantly increase the level of reactive oxygen species (ROS) and deplete glutathione (GSH) upon ultrasonic irradiation, resulting in the loss of glutathione peroxidase-4 (GPX4) activity, which facilitated SDT and ferroptosis to kill glioma C6 cells. Furthermore, the PIOC@CM NPs were intravenously injected after noninvasively opening the BBB via US-MBs, which enhanced the accumulation of the nanosonosensitizer in tumor tissues. Crucially, an attractive phenomenon of the significant reduction in orthotopic gliomas after the second US pulse-triggered SDT and ferroptosis was observed. Taken together, this study presents a novel combinatorial glioma therapeutic strategy based on noninvasive BBB opening with a biomimetic sonotheranostic system-mediated SDT and ferroptosis.

Focused Acoustic Vortex-Regulated Composite Nanodroplets Combined with Checkpoint Blockade for High-Performance Tumor Synergistic Therapy.

The combination of checkpoint blockade with focused ultrasound (FUS) physical therapy can enhance antitumor immune response by improving the precision and efficiency of immunotherapy. However, one of the major disadvantages of conventional FUS treatment is the small lesion size, which prolongs treatment duration. We constructed a focused acoustic vortex (FAV) system with a hollow cylindrical focal region, which exhibited a larger focal region compared to conventional FUS of the same frequency. We developed an all-in-one synergistic therapy against metastatic breast cancer based on integrated FAV double combination sequence-regulated phase-transformation nanodroplets (CPDA@PFH) with checkpoint blockade immunotherapy. A single treatment with FAV + CPDA@PFH resulted in 2.25-fold higher inhibition of tumor growth compared to that with FUS + CPDA@PFH. In addition, FAV-regulated CPDA@PFH combined with ICB induced a systemic immune response that not only inhibited the growth of primary (98.41% inhibition rate) and distal (80.71%) 4T1 tumors but also reduced the progression of lung metastasis. In addition, the synergistic therapy achieved long-term immune memory that effectively prevented tumor growth and improved the survival time of mice. The long-term survival rate of 4T1 tumor-bearing mice treated with FAV + CPDA@PFH + Anti-PD-L1 was 57.14% on day 60 after treatment. Our study is a proof-of-concept of cascade-amplified synergistic tumor therapeutics based on ultrasonic-hyperthermia, cavitation, sonodynamic therapy (SDT), and checkpoint blockade immunotherapy through FAV-regulated CPDA@PFH phase-transformation nanodroplets.

Identification of psychological stressors in cancer patients based on a computer decision support nursing system.

OBJECTIVE: We aim to improve the decision-making process of nursing evaluation, and the purpose of this paper was to introduce nursing outcome classifications based on standardized nursing language, as well as build a comprehensive nursing evaluation decision-making system model based on an artificial neural network and fuzzy comprehensive evaluations. METHODS: Based on the principle and method of the decision support system (DSS), this paper proposed a framework of DSS and developed an intelligent nursing decision support system which integrates expert systems, data, models and knowledge. RESULTS: Taking cancer patients as examples, based on the analysis and comparison of cancer stressors and their frequency of occurrence, this paper found that the 5 major factors for cancer patients' stress events were lack of privacy, attitude of the medical workers, unfamiliar medical workers and uncomfortable temperature in wards. In addition, through the single factor analysis of the stressors, it was found that "the impact of hospitalization on individuals and their families", "the professional level and service attitude of medical workers", and "partial loss of free social contact in the hospital" were all positively correlated with stress level. The degree of cancer patients' participation in treatment decision-making was lower than the expectation of the patients. There was a statistically significant difference between the actual participation and the anticipated participation of cancer patients in nursing decision-making (P < 0.0001). In addition, the system helped patients adapt to the hospital environment as quickly as possible, so that they could feel comfortable in the hospital environment, as well as a relaxed and pleasant with the humanistic environment. CONCLUSION: Cancer patients have a variety of stressors, and the pressure is high. Our computer decision support nursing system assisted nurses to help patients to take positive coping measures to relieve pressure as soon as possible, so as to improve their quality of life.

Retraction: Enhanced anti-tumor efficacy of hyaluronic acid modified nanocomposites combined with sonochemotherapy against subcutaneous and metastatic breast tumors.

Retraction of 'Enhanced anti-tumor efficacy of hyaluronic acid modified nanocomposites combined with sonochemotherapy against subcutaneous and metastatic breast tumors' by Pengying Wu et al., Nanoscale, 2019, 11, 11470-11483, https://doi.org/10.1039/C9NR01691K.

Retraction: Cell membrane based biomimetic nanocomposites for targeted therapy of drug resistant EGFR-mutated lung cancer.

Retraction of 'Cell membrane based biomimetic nanocomposites for targeted therapy of drug resistant EGFR-mutated lung cancer' by Pengying Wu et al., Nanoscale, 2019, 11, 19520-19528, https://doi.org/10.1039/C9NR05791A.

Fluidity and elasticity form a concise set of viscoelastic biomarkers for breast cancer diagnosis based on Kelvin-Voigt fractional derivative modeling.

Cancer progression involves biomechanical changes within transformed cells and the surrounding extracellular matrix (ECM). The viscoelastic features of fluidity and elasticity that are based on a novel Kelvin-Voigt fractional derivative (KVFD) model were found capable of discriminating normal, benign and malignant breast biopsy tissues on the cellular scale. The improved specificity of KVFD model parameters derives from greater accuracy of fitting the entire approaching force-indentation measurement curve ([Formula: see text] > 0.99) compared with traditional elastic models ([Formula: see text] < 0.86). Moreover, model parameters can be interpreted in terms of histopathological features. First, statistical comparisons reveal there are significant differences (p < 0.001) in elasticity E0, fluidity [Formula: see text], and viscosity [Formula: see text] among healthy, benign, and malignant groups. Malignant breast tissues show low-value, broad-distributions in E0 and with high fluidity [Formula: see text] as compared with healthy and benign tissues. Second, histograms of E0 and [Formula: see text] provide distinctive features by fitting to Gaussian mixture (GM) models. The histograms of E0 and [Formula: see text] are best fit by two kernels GM for malignant tissues, indicating that the cells are soft but with high fluidity and the ECM is stiff but with low fluidity. However, the data suggest one-kernel GM model for benign tissue and a patched uniform distribution for healthy tissue. Third, using fluidity [Formula: see text] as the test statistic, the area under the receiver operator characteristic curve (AUC) is 0.701 ± 0.012 (p < 0.0001) for control versus malignant and 0.706 ± 0.013 (p < 0.0001) for benign versus malignant group. Variations in tissue fluidity and elasticity offer a concise set of viscoelastic biomarkers that correlate well with histopathological features.

Ultrasound-Mediated Gene Therapy of Hepatocellular Carcinoma Using Pre-microRNA Plasmid-Loaded Nanodroplets.

The PIK3 CA gene encodes the p110α protein subunit and is one of the most efficient cancer genes in solid and hematological tumors including hepatocellular carcinoma (HCC). There are currently ongoing therapies against tumors based on PIK3 CA inhibition. Because microRNAs (miRNAs) play an important role in post-transcriptional regulation and are also involved in the inhibition of PIK3 CA expression to suppress cancer cell proliferation, overexpression of tumor-suppressive miRNA is a promising therapeutic approach for HCC therapy. The successful and localized delivery of miRNA overexpression vectors (pre-miRNA plasmids) is very important in improving the therapeutic efficacy of this miRNA therapy strategy. In the study described here, submicron acoustic phase-shifted nanodroplets were used to efficiently deliver pre-miRNA plasmid in vitro and in vivo for HCC therapy under focused ultrasound (US) activation. Briefly, six miRNAs, inhibiting PIK3 CA and downregulated in HCC, were selected through summary and analysis of the currently existing literature data. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blot and cell apoptosis assay revealed that pre-miR-139, -203a, -378a and -422a plasmids among the six miRNA overexpression vectors could suppress growth of the hepatoma cell line SMMC-7721. These four pre-miRNA plasmids were then electrostatically adhered to positively charged lipid-shelled nanodroplets to obtain plasmid-loaded nanodroplets (PLNDs). The PLND-generated microbubbles oscillated and even collapsed under US exposure to release the loaded pre-miRNA plasmids and enhance their cellular uptake through consequent sonoporation, that is, formation of small pores on the cell membrane induced by the mechanical effects of PLND cavitation. Fluorescence microscopy results revealed that PLNDs could effectively deliver the aforementioned four pre-miRNA plasmids into SMMC-7721 cells in vitro under 1.2-MHz 60-cycle sinusoid US exposure with a peak negative pressure >5.5 MPa at a 40-Hz pulse repetition frequency. Plasmid delivery efficiency and cell viability positively correlated with the inertial cavitation dose that was determined mainly by peak negative pressure. Furthermore, PLNDs combined with US were evaluated in vivo to deliver these four pre-miRNAs plasmids and verify their therapeutic efficacy in subcutaneous tumor of the mouse xenograft HCC model. The results revealed that the PLNDs loaded with pre-miR-139 and -378a plasmids could effectively suppress tumor growth after US treatment. Thus, combination of pre-miRNA PLNDs with US activation seems to constitute a potential strategy for HCC therapy.

Plasmid-loadable magnetic/ultrasound-responsive nanodroplets with a SPIO-NP dispersed perfluoropentane core and lipid shell for tumor-targeted intracellular plasmid delivery.

Using ultrasound activating contrast agents to induce sonoporation is a potential strategy for effective lesion-targeted gene delivery. Previous reports have proven that submicron nanodroplets have a better advantage than microbubbles in that they can pass through tumor vasculature endothelial gaps by passive targeting; however, they cannot achieve an adequate dose in tumors to facilitate ultrasound-enhanced gene delivery. Additionally, a few studies focused on delivering macromolecular genetic materials (i.e. overexpression plasmid and CRISPR plasmid) have presented more unique advantages than small-molecular genetic materials (i.e. miRNA mimics, siRNA and shRNA etc.), such as enhancing the expression of target genes with long-term effectiveness. Thereby, we constructed novel plasmid-loadable magnetic/ultrasound-responsive nanodroplets, where superparamagnetic iron oxide nanoparticle dispersed perfluoropentane was encapsulated with lipids to which plasmids could be adhered, and branched polyethylenimine was used to protect the plasmids from enzymolysis. Furthermore, in vitro and in vivo studies were performed to verify the magnetic tumor-targeting ability of the plasmid-loadable magnetic/ultrasound-responsive nanodroplets and focused ultrasound enhanced intracellular plasmid delivery. The plasmid-loadable magnetic/ultrasound-responsive nanodroplets, carrying 16-19 plasmids per droplet, had desirable diameters less than 300 nm, and integrated the merits of excellent magnetic targeting capabilities and phase transition sensitivity to focused ultrasound. Under programmable focused ultrasound exposure, the plasmid-loadable magnetic/ultrasound-responsive nanodroplets underwent a phase-transition into echogenic microbubbles and the subsequent inertial cavitation of the microbubbles achieved an ∼40% in vitro plasmid delivery efficiency. Following intravenous administration, T2-weighted magnet resonance imaging, scanning electron microscopy and inductively coupled plasma optical emission spectrometry of the tumors showed significantly enhanced intratumoral accumulation of the plasmid-loadable magnetic/ultrasound-responsive nanodroplets under an external magnetic field. And a GFP ELISA assay and immunofluorescence staining indicated that focused ultrasound-induced inertial cavitation of the plasmid-loadable magnetic/ultrasound-responsive nanodroplets significantly enhanced the intracellular delivery of plasmids within the tumor after magnet-assisted accumulation, while only lower GFP levels were observed in the tumors on applying focused ultrasound or an external magnet alone. Taken together, utilizing the excellent plasmid-loadable magnetic/ultrasound-responsive nanodroplets combined with magnetism and ultrasound could efficiently deliver plasmids to cancer cells, which could be a potential strategy for macromolecular genetic material delivery in the clinic to treat cancer.

IR780 loaded perfluorohexane nanodroplets for efficient sonodynamic effect induced by short-pulsed focused ultrasound.

Inertial cavitation is crucial for the therapeutic effects of sonodynamic. Therefore, approaches that can induce highly efficient inertial cavitation should be of benefit for sonodynamic effect. Our previous study demonstrated that highly efficient inertial cavitation activity can be achieved through the combinatorial use of a short-pulsed focused ultrasound (SPFU) sequence and perfluorohexane (PFH) nanodroplets. Herein, we applied the SPFU sequence and PFH nanodroplets in sonodynamic. A hydrophobic sonosensitizer, IR780 iodine, was loaded inside denatured bovine serum albumin-shelled PFH (PFH@BSA-IR780) nanodroplets. The sonodynamic efficacy was validated by treating HeLa cervical cancer cells. Under SPFU exposure, PFH@BSA-IR780 nanodroplets were highly effective in promoting reactive oxygen species generation and inducing cancer cell death. A significant decrease in cell viability was achieved within just 10 s. Besides the cytotoxicity of ROS, the mechanical bioeffects of inertial cavitation also led to severe cell death resulting from higher acoustic power or the longer treatment time. The application of the SPFU sequence coupled with PFH@BSA-IR780 nanodroplets is a promising strategy for efficient sonodynamic.

Cell membrane based biomimetic nanocomposites for targeted therapy of drug resistant EGFR-mutated lung cancer.

The therapeutic efficacy of anti-cancer nanomedicines is generally constrained due to limited accumulation in the solid tumors. In this study, we developed a biomimetic nano-carrier to enhance the chemo-therapeutic efficacy of doxorubicin and icotinib in a chemo-resistant non-small cell lung cancer (NSCLC) cell line harboring a mutation in the epidermal growth factor receptor (EGFR). The unique nanomedicine was prepared by coating with targeting cancer cell membrane proteins as highly specific ligands. The resulting biomimetic nanoparticles were highly stable and exhibited superior homologous targeting ability in vitro compared with control groups. In a mouse EGFR-mutated NSCLC xenograft model, intravenous injection of the biomimetic nanomedicine led to a high tumour inhibition rate (87.56%). Histopathological analysis demonstrated that the biomimetic nanomedicine had minimal side effects. Taken together, a cancer cell membrane-based biomimetic drug carrier can significantly enhance drug accumulation and improve therapeutic efficacy in cancers.

ROS-Responsive Blended Nanoparticles: Cascade-Amplifying Synergistic Effects of Sonochemotherapy with On-demand Boosted Drug Release During SDT Process.

Sonodynamic therapy (SDT) not only has greater tissue-penetrating depth compared to photo-stimulated therapies, but also can also trigger rapid drug release to achieve synergistic sonochemotherapy. Here, reactive oxygen species (ROS)-responsive IR780/PTL- nanoparticles (NPs) are designed by self-assembly, which contain ROS-cleavable thioketal linkers (TL) to promote paclitaxel (PTX) release during SDT. Under ultrasound (US) stimulation, IR780/PTL-NPs produce high amounts of ROS, which not only induces apoptosis in human glioma (U87) cells but also boosts PTX released by decomposing the ROS-sensitive TL. In the U87 tumor-bearing mouse model, the IR780/PTL-NPs releases the drug at the target sites in a controlled manner upon US irradiation, which significantly inhibits tumor growth and induces apoptosis in the tumor tissues with no obvious toxicity. Taken together, the IR780/PTL-NPs are a novel platform for sonochemotherapy, and can control the spatio-temporal release of chemotherapeutic drugs during SDT.

Enhanced anti-tumor efficacy of hyaluronic acid modified nanocomposites combined with sonochemotherapy against subcutaneous and metastatic breast tumors.

Sonochemotherapy is a promising strategy for inhibiting tumor growth. However, achieving highly targeted and effective sonochemotherapy is still an enormous challenge. In this study, a novel chemotherapeutic-carrying nanocomposite (HPCID) was developed, which can effectively target metastatic cancer cells and provide an enhanced therapeutic effect. In detail, HPCID was composed of hyaluronic acid (HA), carboxyl-terminated PAMAM dendrimer, fluorochrome indocyanine green (ICG), and doxorubicin hydrochloride (Dox). The efficacy of this drug delivery system (DDS) in sonochemotherapy was assessed on the CD44-overexpressing metastatic breast cancer cell line 4T1 both in vitro and in vivo. The HA modification significantly improved the cellular internalization of HPCID, and the degradation of the HA shell by hyaluronidase that is abundant in the 4T1 cells resulted in enzyme-responsive drug release. Under ultrasound (US) stimulation, HPCID produced a high amount of reactive oxidant species (ROS), which induced significant cell apoptosis when combined with chemotherapy. In addition, the administration of HPCID in 4T1 xenograft-bearing mice combined with ultrasonic exposure significantly inhibited tumor growth and pulmonary metastasis, with no systemic toxicity. Taken together, the proposed HPCID-mediated sonodynamic therapy (SDT) is a novel strategy against breast cancer progression and metastasis.

Ultrasound-Responsive Polymeric Micelles for Sonoporation-Assisted Site-Specific Therapeutic Action.

Targeting drug delivery remains a challenge in various disease treatment including cancer. The local drug deposit could be greatly enhanced by some external stimuli-responsive systems. Here we develop pluronic P123/F127 polymeric micelles (M) encapsulating curcumin (Cur) that are permeabilized directly by focused ultrasound, in which ultrasound triggers drug release. Tumor preferential accumulation and site-specific sonochemotherapy were then evaluated. Cur-loaded P123/F127 mixed micelles (Cur-M) exhibited longer circulating time and increased cellular uptake compared to free Cur. With the assistance of focused ultrasound treatment, Cur-M showed tumor-targeting deposition in a time-dependent manner following systemic administration. This was due to enhanced permeabilization of tumor regions and increased penetration of Cur-M in irradiated tumor cells by ultrasound sonoporation. Furthermore, Cur-M self-assembly could be regulated by ultrasound irradiation. In vitro Cur release from mixed micelles was greatly dependent on ultrasound intensity but not on duration, suggesting the cavitational threshold was necessary to initiate subsequent sonochemotherapy. In vivo site-specific drug release was demonstrated in dual-tumor models, which showed spatial-temporal release of entrapped drugs following intratumoral injection. The sonoporation-assisted site-specific chemotherapy significantly inhibited tumor growth and the decrease in tumor weight was approximately 6.5-fold more than without exposure to ultrasound irradiation. In conclusion, the established ultrasound-guided nanomedicine targeting deposit and local release may represent a new strategy to improve chemotherapy efficiency.