718results about "Disrupted materials" patented technology

Sonodynamic therapy systems and methods use short, high-pressure ultrasound pulses that produce small (and therefore clinically safe) increases (up to 1-2° C.) in tissue temperature but nonetheless activate sonodynamic agents, allowing isolated single-cav-itation events to produce therapeutically beneficial effects (e.g., cytotoxicity) on diseased tissue. An escalating sonication strategy may be employed whereby the focal pressure is gradually increased until maximum clinically tolerable parameters such as the degree of heating of intervening tissue (e.g., the skull when treating brain cancer) or undesired induced cavitation effects are reached.

The present invention relates to an immunomicrobubble complex and its uses. The immunomicrobubble complex (IMC) according to the present invention comprises microbubbles conjugated with an antibody, wherein the microbubbles have excellent stability and excellent antibody binding strength, and it has been confirmed that when the immunomicrobubble complex is treated with high-intensity focused ultrasound (HIFU), the anti-tumor effect is significantly enhanced and an immune-enhancing effect is exhibited. Therefore, the immunomicrobubble complex according to the present invention is expected to improve the delivery efficiency of the conjugated antibody and can be used for the diagnosis and treatment of cancer, and exhibits various functions in the field of immunotherapy, including a contrast effect, improvement of half-life, improvement of drug delivery, lymphocyte concentrating effect, cancer immunotherapy, and ultrasound-induced immunotherapy.

The invention belongs to the technical field of biomedical materials, and relates to ultrasonic response adhesion integrated hydrogel as well as a preparation method and application thereof, the hydrogel comprises a hydrogel matrix, an interface anchoring agent and a functional load component; the preparation method comprises the following steps: 1, preparing a hydrogel precursor solution, and preparing a hydrogel matrix into a solution; 2, carrying out mold molding or injection crosslinking on the solution prepared in the step 1 to form hydrogel; 3, preparing an interface anchoring agent solution, and dissolving or dispersing an interface anchoring agent in a solvent to prepare the interface anchoring agent solution; the ultrasonic responsive adhesive hydrogel platform provided by the invention can provide an efficient, controllable and universal solution for tissue adhesion, targeted therapy, wearable attachment and the like in a complex microenvironment, and is suitable for a plurality of clinical scenes such as chronic wound management, surgical postoperative closure, infection control, adhesive bioelectronic fixation, soft tissue engineering and the like.

The present invention relates to sonosensitive liposomes and a method for preparing the same. The sonosensitive liposomes according to the present invention improve the delivery efficiency of encapsulated drugs, and are expected to exhibit various functions in the fields of cancer treatment and drug delivery carriers by improving drug delivery effects through targeted cancer cells when used in combination with ultrasonic treatment.

Hydrogen-bonded framework nanoparticles comprising a chemiluminescent compound (e.g., L-012) are provided and can be used, e.g., for sono-optogenetic treatment of neurodegenerative diseases such as Parkinson's disease. Related in vivo and therapeutic methods are also provided.

The present invention provides ultrasound-responsive liposome nanoparticles and a preparation method and use thereof. The liposome nanoparticles include dimyristoylphosphatidylcholine, 1,2-dioleoyl-3-trimethyl ammonium-propane, distearoylphosphatidylethanolamine-polyethylene glycol, a sonosensitizer, an antibiotic, and perfluoropentane. The liposome nanoparticles are used for the treatment of bacterial biofilm infections. The preparation method involves preparing a liposome film.

The present invention relates to ultrasound (US) mediated delivery of therapeutic agents, such as the delivery of a drug, gene, nanoparticle or radioisotope, using a bi-phasic microparticle system comprising gas microbubbles, emulsion microdroplets and clusters thereof. Thus, the present invention relates to a cluster composition and a pharmaceutical composition, and their use for delivery of therapeutic agents and as a contrast agent for ultrasound imaging. It further relates to methods for delivering such therapeutic agents and to the use of said compositions.

The invention relates to the technical field of nano-drugs, in particular to low-intensity focused ultrasound response nanoparticles for enhancing thrombus targeting and penetration, a preparation method of the nanoparticles and application of the nanoparticles in anti-thrombus treatment. The low-intensity focused ultrasound response nanoparticle for enhancing thrombus targeting and penetration comprises a platelet membrane shell, and a core is formed by wrapping perfluoropentane and L-arginine with polylactic acid-glycolic acid copolymer-polyethylene glycol. The platelet membrane ensures that the nanoparticles specifically target a thrombus part; under the stimulation of LIFU, the nanobubbles penetrate through the deep layer of thrombus, L-arginine is oxidized into L-citrulline, and nitric oxide is formed. Meanwhile, the LIFU triggers liquid-gas phase change and nitric oxide release, the ultrasonic cavitation effect is enhanced through the synergistic effect, thrombus structures including red blood cells, blood platelets and fibrin are specifically attacked, and efficient thrombolysis treatment is achieved. According to the technical scheme, the technical problem that the thrombolysis effect of ultrasonic nanoparticles is not ideal can be solved, and good clinical application prospects are achieved.

An improved method for MRI-guided sonosensitized focused ultrasound treatment of malignant tissue is disclosed herein.

The invention discloses a preparation method of dual-crosslinking ultrasonic response hyaluronic acid hydrogel, and belongs to the field of drug delivery, the preparation method comprises the following steps: taking hyaluronic acid as a raw material, and preparing hyaluronic acid dopamine through amidation reaction; then synthesizing a block polymer poly (polyethylene glycol metacrylic acid-co-4-vinyl phenylboronic acid) through a copolymerization reaction, mixing the block polymer poly (polyethylene glycol metacrylic acid-co-4-vinyl phenylboronic acid) with hyaluronic acid dopamine, dissolving the mixture in deionized water to obtain a mixed solution, preparing drug-loaded iron oxide nano magnetic microbubbles, adding the drug-loaded iron oxide nano magnetic microbubbles into the mixed solution to obtain a hydrogel solution, adjusting the pH value to 5-6, and standing to obtain the hydrogel. The problems that traditional single hyaluronic acid hydrogel is often insufficient in mechanical strength and elasticity are solved, and the prepared hyaluronic acid hydrogel has excellent mechanical strength and structural stability, can release drugs through ultrasound, has a good release effect, also has the characteristics of low toxicity and good biocompatibility, and can be used for preparing the hydrogel. The method has a good application prospect in the field of biological application.

The invention discloses a new medicine application of a local injection acoustic response stent in enhancing ultrasound histotripsy. The acoustic response scaffold (ARS) comprises a scaffold material, fluorocarbon gas or liquid fluorocarbon particles with liquid-vapor phase change capacity, and microbubble cloud in the scaffold generates a strong cavitation ablation treatment effect in a target area under the action of low-frequency and low-sound-pressure ultrasound. Fluorocarbon gas or liquid fluorocarbon particles contained in the ARS form microbubble cloud and ideal cavitation nuclei under low-frequency low-sound-pressure ultrasonic excitation, inertia cavitation resonance is achieved under the ultrasonic action, and then cavitation mechanical damage with local tissue controllable strength is generated. The low-intensity ultrasonic histotripsy has the characteristics of low sound pressure, low sound intensity, high targeting property, small tissue damage outside a target region, simplicity in instrument manufacturing and the like, and the targeting property and the safety of treatment are improved. The method does not need very accurate ultrasonic focusing, reduces the operation difficulty, and has application prospects in multiple medical fields such as prostatic hyperplasia, tumor ablation and tumor immunotherapy.

The invention provides dual-response antibacterial repair-promoting injectable hydrogel as well as a preparation method and application thereof, and belongs to the technical field of biomedical materials. Two-dimensional titanium carbide (TiO2 (at) MXene) with the surface modified with titanium dioxide and a bioactive substance are introduced into a hydrogel matrix to serve as functional additives, TiO2 (at) MXene is a photo-thermal and ultrasonic response material, can emit heat under 808 nm near-infrared (NIR) light irradiation and low-intensity pulsed ultrasound (LIPUS) stimulation, and can generate reactive oxygen species (ROS) for sterilization under LIPUS stimulation; when the temperature of the hydrogel is increased, the bioactive substances can be slowly released from the hydrogel, and cell proliferation and tissue repair are promoted. The hydrogel provided by the invention can be coated on the surface of skin or injected under soft tissue, so that the functions of resisting bacteria in the early stage of inflammation and promoting tissue repair in the later stage are realized.

The invention discloses a preparation method of a cell membrane modified ultrasonic response type copper / ferroptosis activated nano-carrier. The nano-carrier is used for in-vivo and in-vitro treatment of ultrasonically activated tumors. The carrier is used as an ultrasonic activation type copper / iron death activator, and breast cancer cell membrane doped lipid is coated on the outer layer of a copper-iron bimetal organic framework to form nanoparticles with a core-shell structure. The biomimetic copper / ferroptosis activated nano-carrier disclosed by the invention is mainly characterized in that (1) the in-vivo circulation time of the nano-carrier is prolonged by modification of a breast cancer cell membrane, and accumulation of the nano-carrier in breast cancer cells and tissues is improved by virtue of homologous targeting of the nano-carrier; (2) the copper-iron double-metal-doped metal organic framework has a uniform nano structure, and has the potential of effectively catalyzing Fenton / Fenton-like reaction activity and activating a copper / iron death synergistic effect in cells; and (3) depending on the sound-sensitive agent and the oxygen carrier which are loaded by lipid, the nano-carrier has an ultrasonic signal response release behavior, and can simultaneously activate a sonodynamic effect, a copper death process and an iron death process in tumor cells, so that accurate and efficient killing of tumor tissues is realized.

The invention provides an ultrasonic activated blood coagulation targeting tumor selective prodrug as well as a preparation method and application thereof. The blood coagulation targeting tumor selective prodrug has a structure as shown in a formula I. The blood coagulation targeting tumor selective prodrug can trigger a blood coagulation cascade reaction by utilizing tumor vascular injury generated by ultrasonic induction so as to realize targeted anchoring of the drug and inhibit off-target diffusion of an active drug; meanwhile, the prodrug is activated by ultrasound, so that the limitation of tumor heterogeneity on the activation of the prodrug can be overcome. According to the technical scheme, selective enrichment of active drugs in tumors can be effectively improved, and toxicity caused by drug off-target is reduced while tumor growth is remarkably inhibited.

The invention discloses a high-entropy hydrotalcite nanosheet as well as a preparation method and application thereof. Metal in a laminate of the high-entropy hydrotalcite nanosheet comprises Cu, Mn, Co, Ni and Fe, and all the metal exist in the form of ions. The surface of the laminate has positive charges, and the interlayer of the laminate has negative charges; and the size of the hydrotalcite nanosheet is 30 + / -10nm. When the high-entropy hydrotalcite nanosheet is used as a sound-sensitive agent, the high-entropy hydrotalcite nanosheet has nuclear magnetic imaging performance, can generate a large number of active oxygen species in a tumor microenvironment after ultrasonic treatment, and shows an excellent sonodynamic therapy effect. In addition, manganese ions in the hydrotalcite nanosheet can effectively improve the nuclear magnetic imaging effect, and the biocompatibility is good.

The present disclosure is a polyethylene glycol modified zwitterionic fluorescent probe. The core luminescent group of the fluorescent probe of the present disclosure is a heptamethine chain which is connected by a phenoxy bridge and has a rigid ring structure in the center. The two ends of the heptamethine chain are two sulfonic indole groups, and two polyethylene glycol chains are connected with the indole groups. A tumor targeting ligand is connected with a luminescent group through one polyethylene glycol chain and one alkaline amino acid spacer. The probe of the present disclosure can be connected with polypeptides, small molecules and antibodies having a tumor targeting function, thereby achieving near-infrared fluorescence imaging for tumor targeting. The probe of the present disclosure has good druggability, and is extremely suitable for industrial production and clinical promotion.

The present invention relates to: a temperature-sensitive hydrogel for cancer treatment; a photothermal composition comprising the hydrogel as an active ingredient; and a preparation method for the temperature-sensitive hydrogel for cancer treatment. The temperature-sensitive hydrogel of the present invention includes gold nanostars as active ingredients, and thus can generate heat by light irradiation, thereby exhibiting a photothermal therapy effect. In addition, the hydrogel temperature increases so that the release of nitric oxide (NO) from S-nitrosocysteine can be induced. In addition, the temperature-sensitive hydrogel of the present invention includes S-nitrosocysteine as an active ingredient so that, upon a temperature rise due to a photothermal reaction, the penetration of drugs into a tumor site can be improved by the release of NO, and at the same time, apoptosis of cancer cells can be directly caused; and includes an immunotherapy agent as an active ingredient so that tumor size can be effectively suppressed even with the passage of time. Therefore, as a material that enables complex treatment combined with photothermal therapy and immunotherapy, the temperature-sensitive hydrogel of the present invention having the aforementioned effect can be usefully utilized in the field of medicine for cancer treatment.

The present disclosure related to a method of using high frequency sound waves directed toward an acoustically active particle. The high frequency sound waves may be configured to enlarge the acoustically active particle and oscillate the acoustically active particle, thereby facilitating extravasation of an agent to a tissue compartment of a region of interest.

The invention relates to a multifunctional silica plastid integrating chemotherapy, immunotherapy and gas therapy, and relates to a preparation method of the multifunctional silica plastid and application of the multifunctional silica plastid in tumor diagnosis and treatment. The schematic diagram is as shown in the figure, the membrane components comprise conventional phospholipid and complex lipid, a chemotherapeutic drug doxorubicin (DOX) entrapped on a hydrophilic core and Fe3 (CO) 12 entrapped on a hydrophobic core, and the chemotherapeutic drug can be adjusted according to needs and is suitable for broad-spectrum tumor treatment. The drug-loaded silica plastid can generate part of carbon monoxide in a tumor high-concentration hydrogen peroxide (H2O2) environment and release internally-loaded chemotherapeutic drugs. Under the action of ultrasound (US), the multifunctional silicon plastid can realize fixed-point release of chemotherapeutic drugs DOX and carbon monoxide at a tumor site, the enrichment and uptake of the drugs at the tumor site are greatly improved, in addition, the system is combined with the alphaPD-L1 antibody, the immunosuppressive PD-L1 / PD-1 axis can be blocked, T cells are recruited to attack tumors, meanwhile, the immunosuppressive regulatory T cells (Tregs) are reduced, and the tumor treatment effect is improved. The tumor inhibition can be enhanced; the pulmonary metastasis can be obviously reduced.

The invention belongs to the technical field of biological medicines, and particularly discloses a nano-engineering T cell membrane coated nano-particle as well as a preparation method and application of the nano-engineering T cell membrane coated nano-particle. Nanoparticles of a specific structure are constructed based on a phospholipid bilayer bionic nanometer platform through a membrane fusion technology, immune clearance caused by phagocytosis of the nanoparticles by macrophages can be avoided through disguise of a T cell membrane, and the blood circulation time is prolonged; the functions of T cells are recovered through specific blocking of immune checkpoint molecules loaded on the immune checkpoint molecules on corresponding immune checkpoint ligands on tumor cells; under ultrasonic radiation, the nano-particles are gradually decomposed and release the sound-sensitive agent to generate a large amount of active oxygen, so that immunogenic death of tumor cells is promoted, more cytotoxic T lymphocytes are recruited to infiltrate into tumor parts, and the recovery of T cell mediated immune response function is facilitated. The synergistic effect of the sound-sensitive agent and the immune checkpoint protein can effectively inhibit tumor growth, induce a long-term immune memory effect and prevent tumor metastasis and recurrence.

Theranostic targeted ultrasonic blasting nano-bubbles, a preparation method therefor, and use thereof, wherein the nano-bubbles are the targeted drug-gene nano-bubbles miRNA / FTY720 / PFP@PEI-T7 NBs. The nano-bubbles can be used for preparing a thyroid ultrasound diagnostic agent or a drug for treating thyroid cancer.

Disclosed herein is a composition for enhanced ultrasound ablation and methods relating to same. The composition may include a microbubble-microdroplet cluster composition, wherein the microbubble-microdroplet cluster composition may include groups of negatively charged microbubbles and positively charged microdroplets permanently held together by their opposing electrostatic attractive forces to form a single, agglomerated entity.

Compositions and methods for administration of local anesthetics that are delivered by a single injection and enable repeated on-demand or high influx analgesia over extended periods have been developed. Pharmaceutical compositions including an effective amount of one or more sodium channel blockers including site 1 sodium channel blockers, optionally one or more alpha-2-adrenergic agonists, which are optionally encapsulated in liposomes, particles or microbubbles, and one or more triggerable elements are provided. The triggerable elements allow delivery of the encapsulated anesthetic drugs when an appropriate triggering stimuli are applied. Exemplary triggering agents or stimuli include near-infrared irradiation, UV- and visible light, ultrasound and magnetic field. In one embodiment, ultrasound is used to trigger a burst of microbubbles to enhance penetration of local anesthetic.

The present invention relates to methods of producing microbubble drug conjugates, viral gene therapy microbubble drug conjugates, and disease-targeting microbubbles, for clinical and preclinical ultrasound-mediated therapeutic and diagnostic applications. It includes methods to produce viral vector gene therapy microbubble drug conjugates with antibody linkers conjugated to lipid shelled microbubbles that both bind to and neutralize viral vectors such that the viral gene therapy can transduce and effect permanent genetic changes only after ultrasound is used to disassociate the viral gene therapy from microbubbles at diseased regions of the body.

Systems and methods for activating mechanochemical reactions remotely using biocompatible ultrasound in the presence of gas-filled structures are described. The collapse of gas-filled structures is achieved using biocompatible ultrasound. In turn, collapse of the gas-filled structures can mechanochemically activate mechanophore-functionalized polymers in solution. Mechanochemical activation of mechanophore-functionalized polymers under physiological conditions can trigger the release and / or delivery of a variety of cargos with the spatial and temporal precision and deep tissue penetration afforded by focused ultrasound.

The invention belongs to the technical field of medical nano-materials, and particularly relates to a lactoferrin nano-material for sonodynamic regulation and control of blood-brain barrier permeability as well as a preparation method and application of the lactoferrin nano-material. The nanomaterial is nanoparticles LCe6 formed by self-assembly of lactoferrin and chlorin e6, can target brain microvascular endothelial cells, and can temporarily, reversibly and targeting open BBB by using the sonodynamic effect of the LCe6 in combination with transcranial ultrasonic stimulation, so that the accumulation of the nanoparticles LCe6 at a focus part is improved; in addition, the nanoparticle LCe6 also has a targeting property on brain tumor cells, the tumor cells can be accurately killed by utilizing the sonodynamic effect of the nanoparticle under secondary transcranial ultrasound, and the effect of sonodynamic treatment on brain glioma is exerted to the maximum extent; the nanoparticles LCe6 have excellent biocompatibility and low toxicity; according to the invention, the intracerebral delivery efficiency of the drug can be obviously improved, and a novel method for targeting open brain disease BBB is provided.

The invention relates to a preparation method of a tumor microenvironment response type nano drug delivery system, which comprises the following steps: forming MnO2 nanoclusters through biomineralization induction under an alkaline condition, modifying HSA nanoparticles, then loading Ce6 through a carbodiimide method, and finally combining with a PD-L1 antibody by adopting a copper-free click chemistry method to obtain nanoparticles HMC and anti-PD-L1. The nanoparticle can be retained in a tumor tissue in a passive targeting manner through an EPR effect, and is decomposed into Mn < 2 + >, O2 and a small molecule drug through a high H2O2 and low pH microenvironment of the tumor tissue, so that the tumor permeability is greatly enhanced, the tumor immunogenicity is enhanced by combining sonodynamic therapy, the release of a tumor specific antigen and the aging of antigen presenting cells are promoted, and the tumor treatment effect is enhanced. The infiltration of tumor T cells is increased, and cold tumors are changed into hot tumors; the nanoparticles can generate O2 in situ at the same time, and the immunosuppressive ability and drug resistance caused by tumor hypoxia are overcome.

The invention provides an ultrasonic activated azido precursor, a prodrug and application. The precursor and an active drug react and are bonded to obtain the azido prodrug; the bonding group of the active medicine is amino, hydroxyl or sulfydryl; a bonding group of the ultrasonic activated azido precursor is an ester group. Novel ultrasonic activatable groups, namely p-azidobenzyloxycarbonyl and derivatives thereof, are adopted, hydrogen atoms on a benzene ring are substituted to different degrees, the reducing capacity of a precursor can be remarkably improved, azide is effectively reduced into amino through ultrasonic stimulation under the action of TBR and NADH, and then a self-elimination reaction is induced to release active drugs. The structure has the advantages that different types of active drugs (active pharmacodynamic groups can be amino, hydroxyl and sulfydryl) can be bonded through 4-nitrophenyl carbonate, high-selectivity reduction is performed under the triple action of ultrasound, TBR and NADH, active raw drugs are released according to needs, and toxicity reduction and synergism are achieved.

The invention belongs to the technical field of biological medicines, and particularly discloses a bionic nano-vesicle for regulating and controlling neutrophil phenotype in combination with ultrasound, and a preparation method and application of the bionic nano-vesicle. The bionic nano-vesicle provided by the invention can be broken under the action of high-concentration glutathione existing in a tumor tissue microenvironment to release the sound-sensitive agent and functional siRNA, and under the action of US irradiation, the sound-sensitive agent is activated to generate a large amount of ROS, promote tumor cell DNA breakage, generate a large amount of double-stranded DNA, activate APC and promote IFN-beta release, so that the tumor tissue microenvironment is inhibited. The released functional siRNA can promote the N2-type neutrophile granulocyte to become N1-type neutrophile granulocyte, and the released functional siRNA can prevent the N1-type neutrophile granulocyte from being reversed to the N2-type neutrophile granulocyte again, so that the regulation and control on the phenotype of the neutrophile granulocyte are realized; under catalysis of CAT rich in the thylakoid membrane, H2O2 overexpressed by tumor tissue is decomposed into oxygen, the tumor hypoxia microenvironment can be relieved, and the tumor treatment effect can be improved.

The invention provides a preparation method of a drug carrier combined with ultrasonic transdermal drug delivery, according to the method, a micro-fluidic chip is used, an oil phase solution and a water phase solution can be accurately treated under a micro-scale through a micro-fluidic technology, drug carriers with different particle sizes are prepared, the particle sizes are uniform and controllable, and the repeatability is good. The drug carrier disclosed by the invention can be combined with ultrasound to realize accurate transdermal drug delivery, and under the action of the ultrasound, according to the obvious difference of the drug carriers with different characteristics in rupture time and acting force, the delivery sequence, depth and structural layer of the content of the drug carrier are accurately adjusted, so that the controllable release and accurate delivery of the drug are realized.