100 results about "Bone targeting" patented technology

Manganese-doped hollow mesoporous silica nanoparticles loaded with curcumin and an application in periodontal bone tissue repair are provided in the present disclosure, belonging to the technical field of targeted delivery of nanoparticles and bone tissue regeneration. In the present disclosure, alendronate is grafted on the surface of silica nanoparticles to achieve bone targeting, manganese is doped on the nanoparticles by a chemical method, and curcumin is wrapped in the nanoparticles.

The invention provides a compound with a structure as shown in a formula (I). The compound can be used as a polyphenol organic ligand to be self-assembled with metal ions to form metal polyphenol nanoparticles. The nano-particles have a bone targeting effect, are safe, effective, stable and uniform, can realize whole-body transfer, can be degraded in a bone pathology microenvironment, have regulation and control effects on bone resorption and bone formation, can cooperatively regulate and control bone balance, and have a great application prospect in the field of bone diseases such as osteoporosis. # imgabs0 #

The invention discloses an oligonucleotide intracellular nano delivery system based on polypeptide modification and application thereof. The system is composed of a periostin targeting sequence (SDSSD), a matrix metalloproteinase 2 (MMP2) response sequence (GPAGLLG), a cell penetrating sequence (RRRRRRRR, R9), a reactive oxygen species (ROS) scavenging and adhesion enhancing group (Gly-DOPA)) and a terminal dibenzocyclooctyne (DBCO) modified engineered polypeptide SDSSD-PEG5-YGFGG-GPAGLLG-R9-(G-DOPA) 3-K4-C-DBCO, and a target oligonucleotide miRNA-26a-A5-Azido modified by 5-polyadenylic acid (AAAAA) and an azide group (Azido), and the target oligonucleotide miRNA-26a-A5-Azido, the target oligonucleotide and assembling through a click chemical reaction and a non-covalent interaction. The nano system has good bone targeting, enzyme responsiveness, intracellular delivery effect and biological safety, can realize stable and efficient delivery of therapeutic oligonucleotides in vivo, and significantly improves the utilization efficiency and therapeutic potential of oligonucleotides. The oligonucleotide intracellular nano delivery system has a wide application prospect in the fields of clinical transformation and precise treatment of oligonucleotide drugs.

The present invention relates to a nanomaterial for preventing tumor bone metastasis, a preparation method therefor, and use thereof. The present invention has discovered a spatiotemporal coupling interaction between tumor cells and osteoclasts, and provides a tumor-bone initial metastasis behavior-targeting strategy which can accurately prevent tumor metastasis on the basis of the source, and can avoid drug resistance and biochemical drug resistance. On this basis, the present invention designs a physical killing nanomaterial targeting tumor-osteoclast conjugates, the nanomaterial being a bone targeting group-modified nanovesicle encapsulating a carbonate compound and a phosphate compound. The nanomaterial can be effectively concentrated in bone tissue; when tumor cells are activated, the acid secretion function of tumor-related osteoclasts in nearby tumor-osteoclast conjugates which are in contact with the tumor cells triggers the carbonate compound to generate carbon dioxide gas and promotes the release of the phosphate compound, which forms calcium phosphate crystals with calcium ions so as to kill nearby tumor cells, thus achieving a specific very-early tumor metastasis inhibition effect.

The invention relates to the technical field of biomedical materials, in particular to an alendronate-modified ZIF-8 encapsulated TPP-carbon dot bone targeting nano-material and a preparation method and application thereof.The alendronate-modified ZIF-8 serves as a carrier, TPP-modified carbon dots are encapsulated in the carrier, citric acid, urea and cerium salt serve as raw materials of the TPP-modified carbon dots, and the alendronate-modified ZIF-8 encapsulated TPP-carbon dot bone targeting nano-material is prepared through a one-step method. After cerium-doped carbon quantum dots are synthesized through a hydrothermal method, TPP is grafted through an amide method, alendronate endows the material with a bone targeting function, and TPP modified carbon dots endow the material with antioxidant and mitochondrial targeting functions. According to the invention, the bone targeting property is excellent, and bone focuses are efficiently enriched; the anti-oxidation and anti-inflammatory capacities are high, and the infected microenvironment can be improved; zIF-8 packaging is stable, and functional components can be controllably released; multiple components cooperate to promote bone repair, accumulation of non-target organs is little, and the composition is safe, reliable and suitable for treatment of various bone-related diseases.

Among other things, the present disclosure provides antibodies and antigen-binding fragments thereof, conjugates, compositions, and methods thereof that can be used for various purposes, including treating conditions, disorders, or diseases including cancer, e.g., prostate cancer. In some embodiments, antibodies and antigen-binding fragments thereof comprise one or more bone-targeting moieties, e.g., one or more bone-targeting peptides. In some embodiments, antibodies and antigen-binding fragments thereof, conjugates, compositions, and methods thereof can be used to treat bone metastases.

The present disclosure relates to bone targeting therapeutic conjugates and uses thereof. In particular, the disclosure relates to bone targeting therapeutic conjugates comprising a therapeutic antibody for treatment of a bone disease and a bone targeting moiety.

The invention provides hypoxia regulation exosome hydrogel and a preparation method and application thereof in bone defect repair, and compared with the prior art, the hypoxia regulation exosome hydrogel provided by the invention has the advantages that the exosome cultured by 3D stem cells modified by superparamagnetic ferroferric oxide nanoparticles is loaded on the GelMA hydrogel modified by bone targeting polypeptide, and the preparation method is simple. The intelligent oxygen-producing gel is innovatively constructed by skillfully utilizing the relationship between hypoxia and ROS generation according to the challenge that the hypoxia microenvironment of a bone defect part is closely followed. According to the hydrogel disclosed by the invention, osteogenesis regeneration is promoted by regulating and controlling a Wnt / beta-catenin pathway in osteoblasts, so that hypoxia and oxidative stress microenvironments are safely, efficiently and intelligently improved at injured parts. And the adhesion to the defect part is improved, and the problem that the superparamagnetic ferroferric oxide nanoparticles are difficult to effectively retain at the defect part is solved.

The invention relates to the field of nutritional health food, and discloses a casein modified active peptide for promoting bone repair and a preparation method thereof.The structure of the active peptide sequentially comprises a bone targeting sequence with high affinity to hydroxyapatite, a casein phosphopeptide core sequence capable of chelating calcium ions, a casein phosphopeptide core sequence capable of chelating calcium ions, a casein phosphopeptide core sequence capable of chelating calcium ions, a casein phosphopeptide core sequence capable of chelating calcium ions and a casein phosphopeptide core sequence capable of chelating calcium ions from the C-terminal to the N-terminal. The digestion sequence can be specifically hydrolyzed by matrix metalloproteinase, and the alkynyl functional group is used for covalent cross-linking. The active peptide can be mixed with an azido-containing multi-arm cross-linking agent, and hydrogel can be rapidly formed under physiological conditions through cycloaddition reaction. The system can be gelated in situ and anchored to a bone defect part in a targeted manner, and is triggered by a specific enzyme in a pathological microenvironment to controllably release active peptide fragments capable of chelating calcium ions, so that the concentration of local mineral ions is adjusted, the cell living environment is improved, and an effective new way is provided for promoting bone repair.

The present invention belongs to the technical field of cell membrane surface engineering, and specifically relates to a DNA nanosheet for enhancing the bone targeting ability of MSCs, its preparation method and application. The preparation method includes the following steps: mixing a circular scaffold strand and staple strands to obtain a rectangular DNA origami; modifying a maleimide group at the 3'-end of a bone targeting peptide to obtain a maleimide group-modified bone targeting peptide, and mixing the maleimide group-modified bone targeting peptide with a 5'-thiol-modified short chain to obtain a bone targeting peptide-short chain; modifying cholesterol on a DNA short chain to obtain a cholesterol-short chain; mixing the rectangular DNA origami, the bone targeting peptide-short chain and the cholesterol-short chain to obtain a DNA nanosheet for enhancing the bone targeting ability of MSCs. The DNA nanosheet can be used to strengthen MSCs, thereby preparing drugs for degenerative diseases.

The invention relates to the field of high polymer materials and medical engineering, in particular to a high polymer nanoparticle with bone targeting, acid environment neutralization and oxidation resistance characteristics and a preparation method of the high polymer nanoparticle. The polymer nanoparticle is prepared from the following raw materials: a zoledronic acid modified polycaprolactone-polypeptide copolymer, the chemical structural formula of the copolymer is as follows: # imgabs0. The polymer nanoparticles prepared by taking the zoledronic acid modified polycaprolactone-polypeptide copolymer as a raw material have the advantages of bone targeting, excellent oxidation resistance and capability of neutralizing an acid environment. The polymer nanoparticles can exert significant efficacy (oxidation resistance and acid environment neutralization) for treating osteoporosis only by means of intrinsic activity of the materials of the polymer nanoparticles, so that a series of toxicity problems possibly caused by traditional drugs are substantially reduced fundamentally, and a brand new scheme is provided for treatment of osteoporosis.

The invention discloses myricetin-loaded bone-targeted magnetic composite nanoparticles and a preparation method thereof. The preparation method comprises the following steps: step 1, preparing nanoparticles taking ferroferric oxide as an inner core; step 2, preparing magnetic mesoporous silica nanoparticles with ferroferric oxide as an inner core according to the nanoparticles prepared in the step 1; step 3, performing amination modification treatment on the surfaces of the magnetic mesoporous silica nanoparticles prepared in the step 2 to obtain magnetic mesoporous silica modified nanoparticles; step 4, preparing a ketal thiol-polyethylene glycol-aspartic acid hexapeptide molecule; and step 5, loading myricetin on the magnetic mesoporous silica modified nanoparticles prepared in the step 3, and blocking myricetin by using the ketal thiol-polyethylene glycol-aspartic acid hexapeptide molecules prepared in the step 4 after loading. The invention further discloses application of the compound in image tracing in osteolysis and treatment drugs.

The invention relates to the technical field of preparation of bone cement, and particularly discloses a preparation method of a photo-thermal response type gold nanorod-bone cement composite material. The method comprises the following steps: synthesizing a gold seed solution; constructing a growth solution; controlling the growth of the nanorod; gradient centrifugal purification; carrying out surface ligand exchange (sulfydryl-PEG); preparing a bone cement composite material; curing and forming; gold nanorods (GNRs) are uniformly embedded into a polymethyl methacrylate (PMMA) bone cement matrix, so that the problems that free nanorods are easy to migrate and poor in bone targeting are solved. The local temperature can be accurately controlled, and damage to surrounding tissues is avoided. According to the invention, immunogen cell death (ICD) can be effectively induced, and anti-tumor immune response can be activated. According to the invention, enough mechanical support can be provided, and the stability after implantation is ensured.

The application belongs to the technical field of bioactive nanomaterials, and particularly relates to a metformin nanomaterial, a preparation method and application thereof. The average hydrodynamic diameter of the nanomaterial is less than 500 nm, and the nanomaterial is prepared by a preparation method comprising the following steps: self-assembly of metformin and polyphenols to obtain metformin-polyphenol nanoparticles; reaction of bisphosphonate and polyethylene glycol to obtain bisphosphonate-polyethylene glycol organic segments; and reaction of the metformin-polyphenol nanoparticles and the bisphosphonate-polyethylene glycol organic segments to obtain the nanomaterial. The metformin, polyphenol, polyethylene glycol and bisphosphonate are prepared into the metformin-loaded nanomaterial through specific reactions, the systemic delivery of metformin is realized, the efficacy and bioavailability of metformin on osteoporosis are improved, and the bone targeting of metformin is also improved.

The present application relates to the field of high polymer material and medical engineering, and particularly relates to a high polymer nanoparticle with bone targeting, neutralizing acidic environment and antioxidant properties and a preparation method thereof. The preparation raw material of the high polymer nanoparticle comprises a zoledronic acid modified polycaprolactone-polypeptide copolymer, and a chemical structural formula of the copolymer is shown as follows: The high polymer nanoparticle prepared by using the zoledronic acid modified polycaprolactone-polypeptide copolymer as the raw material has the bone targeting, excellent antioxidant property and the ability of neutralizing acidic environment. The high polymer nanoparticle can exert the significant therapeutic effect (antioxidant, neutralizing acidic environment) of osteoporosis only by relying on the inherent activity of the material itself, so that a series of toxicity problems possibly caused by traditional drugs are fundamentally and greatly reduced, and a new scheme is provided for the treatment of osteoporosis.

The invention belongs to the technical field of biological medicine, and particularly relates to multiple myeloma targeting nano microspheres and application thereof. The invention provides a delivery system for targeting multiple myeloma, the delivery system has different targeting molecules for bone targeting and cancer cell targeting, and multiple myeloma cells in a bone marrow microenvironment can be targeted. Furthermore, the delivery system is carried on the Selinexor, so that the selective delivery of the Selinexor on myeloma cells and affected bone tissues can be enhanced. In-vivo studies show that the delivery system significantly improves the treatment effect of MM. Malignant proliferation of myeloma cells is effectively inhibited, the bone density is increased, the bone microstructure is improved, and bone deterioration in an MM mouse model is relieved. The method for delivering the anti-MM drug through the dual-targeting nanoparticles represents an innovative strategy, MM cancer cell targeting and cancer microenvironment bone targeting are combined, and the method is never applied to MM treatment before.

The invention provides a bone targeting nano composite carrier, a bone targeting nano composite drug and a preparation method and application of the bone targeting nano composite carrier and the bone targeting nano composite drug, and belongs to the technical field of biological medicine, the bone targeting nano composite carrier comprises epigallocatechin gallate and E7 targeting peptide, and the mass ratio of the epigallocatechin gallate to the E7 targeting peptide is 1: (1.5-2.5); the epigallocatechin gallate and the E7 targeting peptide are connected through a condensation reaction. According to the invention, the bone-targeted nano composite carrier is used for entrapping an osteogenic induction component, and a bone-targeted nano composite drug is obtained through self-assembly. According to the invention, triple functions of osteogenesis promoting drugs, anti-inflammatory / anti-oxidation components and active targeting are integrated, and the bone-targeting nano composite drug not only can directly stimulate bone formation, but also can fundamentally improve the crucial pathological microenvironment in diabetic osteoporosis.

The invention relates to the technical field of nano-micelles, in particular to rifapentine-loaded bone targeting nano-micelles as well as a preparation method and application thereof.The rifapentine-loaded bone targeting nano-micelles are prepared by accurately controlling a synthesis process (shading, catalyst ratio, temperature and feed ratio) of a bone targeting nano-micelle carrier (ALN-PLGA-mPEG) modified by alendronate sodium (ALN). The bone targeting ability of alendronate sodium (ALN) is combined with the drug loading and long circulation advantages of polymer mPEG-PLGA micelles to construct a bone targeting nano-micelle carrier (ALN-PLGA-mPEG), so that the obtained rifapentine-loaded bone targeting nano-micelle (ALN-PLGA-mPEG (at) RPT) can significantly improve the bone targeting and slow release performance, and provides a new strategy with high efficiency and low toxicity for precise treatment of bone tuberculosis.

The invention discloses a bone targeting forsythiaside A loaded exosome and a preparation method and application thereof, and relates to the technical field of biomedicine.The preparation method comprises the following steps that bone marrow mesenchymal stem cells are separated and cultured, and GLG1 is over-expressed through a molecular cloning technology to obtain GLG1-BMSCs; the exosome GLG1-Exos of the GLG1-BMSCs is collected through an ultracentrifugation method; and loading forsythiaside A into the exosome through an ultrasonic method and an extrusion method to obtain the GLG1-Exos-FTA. The traditional Chinese medicine active ingredient forsythiaside A is loaded, and forsythiaside A is delivered to bone marrow in a targeted manner, so that the effect of preventing and improving diabetic osteoporosis is achieved; due to the targeting effect, the bioavailability of forsythiaside A can be enhanced, and meanwhile, the curative effect of resisting diabetic osteoporosis is improved. Experiments show that the loading rate of forsythiaside A of the GLG1-Exos-FTA reaches 36.9%, the particle size distribution peak value is 122.4 nm, and the GLG1-Exos-FTA has typical exosome characteristics and bone targeting, and can significantly improve the bone microstructure of diabetic osteoporosis mice.

The invention provides an application of a functional polymer and / or a pharmaceutically acceptable salt thereof in preparation of a medicine for treating osteoporosis and / or osteosarcoma. Compared with the prior art, the functional polymer provided by the invention is divided into three parts, and the phospholipid part has the capability of being inserted into the surface of a cell membrane, so that the affinity of a drug and the cell membrane can be improved; the polyethylene glycol part can improve the water solubility of the whole material and the long circulation capability of the whole material in blood, prolong the retention period of the medicine in circulation and improve the utilization degree; the diphosphonate part has a bone targeting effect, so that the medicine can be preferentially positioned at the osteoporosis part, the osteoclast function is inhibited, a relatively good treatment effect on osteoporosis is achieved, and diphosphonate can also induce calcium ion deposition and form a physical barrier around osteosarcoma to inhibit osteosarcoma development.

The invention discloses a bone targeting exosome polypeptide delivery system based on a biological orthogonal strategy and a preparation method and application thereof, and relates to the technical field of biological medicine and drug delivery. The bone targeting exosome polypeptide delivery system based on the biological orthogonal strategy comprises an engineered exosome as a carrier and an osteogenesis-promoting therapeutic polypeptide, wherein the osteogenesis-promoting therapeutic polypeptide is anchored on the membrane surface of the engineered exosome; a fusion protein is displayed on the membrane surface of the engineered exosome, and the fusion protein is formed by fusing a bone targeting ligand and an industrial exosome transmembrane scaffold protein; the osteogenesis-promoting therapeutic polypeptide is connected with the industrial exosome through the flexible spacer arm, and the membrane surface steric hindrance is reduced through the flexible spacer arm so as to improve the accessibility of the active fragment of the polypeptide; the delivery system provided by the invention can improve the targeted enrichment and treatment efficiency of osteogenesis promoting drugs in bone tissues, and is suitable for intervention of bone metabolism related diseases such as osteoporosis, delayed fracture healing, bone defects and the like.

Described herein are bisphosphonate oxazolidinone compounds, and conjugates and pharmaceutical formulations thereof, that can include a bisphosphonate and an oxazolidinone (or an oxazolidinone antimicrobial or antibiotic agent, substituent or derivative thereof), where the oxazolidinone can be releasably coupled to the bisphosphonate. Also provided herein are methods of making and methods of using the bisphosphonate oxazolidinone compounds, conjugates and pharmaceutical formulations thereof. Also provided herein are methods of use of the compounds, conjugates and formulations for treating a bone disease or for use in preparing a formulation for the treatment a bone disease.

The invention relates to the technical field of biological materials, in particular to bone targeting nanoparticles and a preparation method and application thereof.The preparation method comprises the steps that a curcumin organic solution, an icariin organic solution, an alendronate sodium solution and a DSPE-PEG-NHS solution are prepared; under the stirring condition, dropwise adding the icariin organic solution into the curcumin organic solution, continuously stirring for reaction after dropwise adding is completed, and self-assembling to form a curcumin-icariin intermediate; dispersing the curcumin-icariin intermediate in deionized water to obtain a dispersion liquid; and adding an alendronate sodium solution and a DSPE-PEG-NHS solution into the dispersion liquid, carrying out stirring reaction for a preset time, and carrying out dialysis treatment to obtain the bone-targeted nanoparticles. Various active ingredients with different action mechanisms can be integrated into a single nano-carrier, so that synergistic interaction and targeted delivery are realized.

The invention belongs to the technical field of biological medicine, and relates to a bone targeted drug liposome as well as a preparation method and application thereof, the bone targeted drug liposome is prepared from the following raw materials: phospholipid, cholesterol, PEG (polyethylene glycol), a targeted group and a drug; the phospholipid and the cholesterol form a lipid core layer, the PEG of which the tail end is coupled with the targeting group is connected to the surface of the lipid core layer, and the drug is encapsulated in the lipid core layer. The delivery efficiency of the drug is remarkably improved through modification of the targeting group, the solubility and stability of the drug can be improved through the liposome, the slow release effect is achieved, and the drug effect persistence is improved.

The invention provides a near-infrared light NIR response-based dual-regulation nano drug delivery system and application thereof, the nano drug delivery system takes mesoporous silica as a carrier, and alendronate sodium is coupled on the surface of the carrier to increase bone targeting; mesopores in the carrier are blocked by rhodamine RH, nitric oxide NO can be consumed to generate rhodamine B, and bioactive drugs in the carrier are released. The invention constructs a systemic drug carrier with bone targeting and diabetic bone microenvironment response release, and solves the problems that the bone healing ability of diabetic patients is significantly reduced, and traditional local treatment is difficult to effectively improve systemic bone microenvironment disorder; the problems that an existing local drug system cannot be released according to needs, local NO and NO in bone marrow are difficult to efficiently remove, and macrophages are difficult to transform to repair-promoting M2 type are solved.

The invention belongs to the technical field of bioactive nano materials, and particularly relates to a metformin nano material as well as a preparation method and application thereof. The average hydrodynamic diameter of the nano material is less than 500 nm, and the nano material is prepared by the preparation method comprising the following steps: self-assembling metformin and a polyphenol compound to obtain metformin-polyphenol nano particles; the preparation method comprises the following steps: reacting bisphosphonate with polyethylene glycol to obtain a bisphosphonate-polyethylene glycol organic chain segment; the metformin-polyphenol nano particles and the diphosphonate-polyethylene glycol organic chain segment are subjected to a reaction, and the nano material is obtained. According to the invention, the metformin, the polyphenol, the polyethylene glycol and the bisphosphonate are subjected to a specific reaction to prepare the metformin-loaded nano material, so that the whole-body delivery of the metformin can be realized, the curative effect and bioavailability of the metformin on osteoporosis are improved, and meanwhile, the bone targeting property of the metformin is improved.

The invention discloses a naringin carbon quantum dot-based bone-targeting nanocomposite as well as a preparation method and application thereof. The preparation method comprises the following steps: 1, preparing naringin-derived carbon quantum dots (N-CQDs); 2, preparing hybrid silicon dioxide / hydroxyapatite nano particles MH; (3) preparing amino functionalized MH nano particles MH-NH2; 4, adding the activated N-CQDs solution into the MH-NH2 solution, and carrying out stirring reaction at room temperature to prepare MH-CQDs; and 5, dispersing the NHS-PEG-Mal into the MH-CQDs solution, slowly stirring, and dialyzing after the reaction is completed, so as to obtain the P-coated MH-CQDs. According to the nano-composite disclosed by the invention, a natural drug naringin with osteogenic activity is creatively converted into N-CQDs with a pharmacological function and a fluorescent tracing capability, and the N-CQDs are combined with a bionic silicon dioxide-hydroxyapatite substrate, so that the essential fusion of a'drug-probe 'function is realized.

The invention discloses a preparation method and an application of a bone targeting catechin-strontium metal polyphenol nano particle. The system takes a metal-polyphenol network (MPN) formed by coordination self-assembly of strontium ions and catechin as a core, and tetracycline is modified on the surface of the MPN to construct a bone targeting functional layer. The MPN structure can significantly enhance the loading efficiency and physiological stability of catechin, and the tetracycline modification on the surface endows the nanoparticles with excellent bone targeting ability. When reaching an osteoporosis focus, the nanoparticles can respond to a local weakly acidic microenvironment and controllably release catechin, and exert antioxidant and anti-inflammatory effects, thereby reversing a pathological microenvironment unfavorable for bone regeneration. Meanwhile, the MPN skeleton is gradually degraded in vivo, and the released Sr < 2 + > can promote proliferation and differentiation of pre-osteogenic cells, inhibit the activity of osteoclasts and promote formation of new bones. The system integrates bone targeting, microenvironment response drug release, immunoregulation and ion regulation treatment, and provides a new strategy for precise treatment of osteoporosis.

The invention discloses a bone-targeted probiotic external vesicle and application thereof, and belongs to the technical field of bioengineering. The bone-targeted probiotic external vesicles are prepared by the following method: introducing a coding gene of CXCR4, a coding gene of DSS6 and a coding gene of SAE1 into probiotics through a genetic engineering technology to construct recombinant engineering bacteria; and culturing the recombinant engineering bacteria, and collecting the probiotic external vesicles. The bone targeting probiotic outer vesicle is applied to preparation of a preparation with a bone targeting function. The bone targeting probiotic external vesicle has a bone marrow targeting function, an osteoblast targeting function and a function of promoting osteoblast osteogenic differentiation, and can be used for treating bone aplastic disorder related diseases.

The application discloses a bone-targeting protein conjugated chelating agent and a preparation method and application thereof, and belongs to the technical field of biological medicines.The bone-targeting protein conjugated chelating agent is constructed through gene engineering and chemical conjugation technology, the chelating agent is covalently connected by a bone-targeting fusion protein and a small molecule chelating agent, the bone-targeting fusion protein part is composed of a bone-targeting peptide, a cell-penetrating peptide and a Halo tag protein, and the protein molecule can efficiently pass through the cell membrane to reach the bone tissue; the small molecule chelating agent is isothiocyanobenzyl DTPA, and can efficiently undergo nucleophilic addition reaction with lysine residues of the bone-targeting fusion protein under weak alkaline conditions to generate the bone-targeting protein conjugated chelating agent.The chelating agent has the targeting ability to the bone tissue, can be complexed with heavy metal ions deposited in the bone, and realizes precise chelation of the heavy metal ions deposited in the bone.