44 results about "Macrophage targeting" patented technology

The invention discloses bioactive macroporous hydrogel as well as a preparation method and application thereof. The bioactive macroporous hydrogel comprises hydrogel particles and a bioactive load loaded on the hydrogel particles, the hydrogel particles are obtained by mechanically extruding a hydrogel matrix, and the hydrogel matrix is formed by compounding sodium alginate, agarose and methacrylated hyaluronic acid through hydrogen bond crosslinking and photo-crosslinking; the bioactive load comprises: a) small extracellular vesicles of which the surfaces are modified with macrophage targeted CRV peptides; and b) a PLGA (poly (lactic-co-glycolic acid)) microsphere loaded with a cartilage inducer Kartogenin. The bioactive macroporous hydrogel disclosed by the invention has an internally communicated macroporous network, is beneficial to cell infiltration, blood vessel ingrowth and nutrient substance diffusion, and overcomes the defects that the traditional hydrogel is small in pore size and limits cell behaviors. According to the bioactive macroporous hydrogel disclosed by the invention, dual bioactive loads are adopted to synergistically promote tendon-bone healing, so that the treatment effect is better.

The invention discloses an application of a tumor-associated macrophage targeting nanoprobe in ultrasensitive magnetic resonance molecular imaging of in-vivo in-situ lung cancer. The tumor-associated macrophage targeting nanoprobe prepared by the method provided by the invention is loaded with water-insoluble supramolecular celopphane, so that Xe'molecular cage 'celopphane can be uniformly dispersed in water and a biological system, and is used for in-vivo hyperpolarized 129Xe magnetic resonance imaging. According to the nanoprobe, mannose modification is carried out on the surface of the nanoprobe, so that the nanoprobe can effectively target tumor-related macrophages in a tumor area, and targeted detection of in-situ lung cancer tumors is realized; the surface of the nanoprobe is subjected to near-infrared fluorescence molecular modification, so that fluorescence / magnetic resonance bimodal detection of solid tumors can be realized. In combination with the advantage that local drug concentration can be improved by pulmonary drug delivery, a strong 129Xe magnetic resonance signal of the developed probe can be directly detected in vivo, and in-vivo 129Xe magnetic resonance molecular imaging is realized on an in-situ lung cancer model mouse through a direct sampling imaging mode.

The invention discloses a coupling molecule with an effect of promoting macrophages to selectively swallow extracellular goods as well as a preparation method and application of the coupling molecule, and belongs to the technical field of biological medicines. The coupling molecule disclosed by the invention is a double-targeting polypeptide and consists of a macrophage targeting peptide fragment, a linker and a target cell targeting peptide fragment, wherein the target cell targeting peptide fragment comprises peptide fragments targeting tumor cells and apoptotic cells. One end of the dual-targeting polypeptide is connected with macrophages, the other end of the dual-targeting polypeptide is connected with tumor cells / apoptotic cells, and the interaction between the macrophages and the tumor cells / apoptotic cells is improved in a molecular glue mode. Aiming at tumor cells, the dual-targeting polypeptide can enhance the phagocytosis and killing effects of macrophages on the tumor cells under the action of a CD47 antibody, so that the anti-tumor effect is achieved; aiming at apoptotic cells, the dual-targeting polypeptide can promote the interplant effect of macrophages, so that the anti-inflammatory effect is achieved. Therefore, the dual-targeting polypeptide disclosed by the invention has relatively good drug development potential.

Compositions for downregulating Zeb2 in macrophages are provided. Accordingly, there is provided a composition comprising an agent capable of downregulating expression and / or activity of Zeb2 attached to a macrophage-targeting moiety or encapsulated in a particle comprising a macrophage-targeting moiety. Also provided are methods of prognosing and treating an inflammatory disease.

The invention belongs to the technical field of bioengineering, and provides a drug-loaded targeted nano platform for targeted delivery of ZIF-8 drug-loaded nanoparticles by macrophages, a preparation method and an application, aiming at the technical problem that complications are easily caused by the existing treatment means of endometriosis, so that the invention provides a drug-loaded targeted nano platform for targeted delivery of ZIF-8 drug-loaded nanoparticles by macrophages, and a preparation method and application of the drug-loaded targeted nano platform. According to the invention, the ZIF-8 nano-particles and the drugs aiming at the energy metabolism level are combined to be used as the carrier, so that endometriosis cells with acidic cell microenvironment can be targeted, drug controlled release can be realized in the acidic environment of lesions, and the effective uptake of the endometriosis cells to the drugs is enhanced, thereby effectively increasing the uptake rate and the drug concentration at the target position, and improving the curative effect of the drug on the endometriosis cells. Meanwhile, the distribution of the medicine in normal tissues or cells is reduced, and the toxic and side effects of the medicine are reduced; and through the design of combining the macrophages with the ZIF-8 nano-particle carrier, the drug targeting property of the ZIF-8 nano-particle carrier can be obviously improved.

The invention discloses a si-TGM2-loaded macrophage targeting nano-material as well as a preparation method and application thereof, relates to the technical field of biological targeting, and aims at solving the problem that a macrophage targeting nano-drug for inhibiting severe acute pancreatitis aiming at a TGM2 target is lacked in the prior art. The technical key points of the invention are as follows: the si-TGM2-loaded macrophage targeting nano material is provided, the si-TGM2-loaded macrophage targeting nano material is a lactoferrin modified cationic lipid nucleic acid drug, and the cationic lipid nucleic acid drug is prepared by coating si-TGM2 as shown in SEQ.ID. NO.1 with a cationic liposome. The si-TGM2-loaded macrophage targeting nanometer material disclosed by the invention has a wide application prospect in preparation of an acute pancreatitis diagnostic kit and a medicine.

The invention discloses an HSP70-targeting chimeric antigen receptor-macrophage and application thereof in treatment of noise-induced hearing loss, an extracellular domain of the HSP70-targeting chimeric antigen receptor comprises an HSP70 specific binding fragment, an intracellular domain comprises an IL-4 signal channel functional element, a signal switch type CAR structure of the HSP70 is formed, and the macrophage can be used for treating noise-induced hearing loss, so that the HSP70-targeting chimeric antigen receptor-macrophage can be used for treating noise-induced hearing loss. The HSP70-targeted chimeric antigen receptor-macrophage can be used for preparing the HSP70-targeted chimeric antigen receptor-macrophage, is used for mediating polarization of the macrophage to an M2 type and exerting an anti-inflammatory function, is proved to be capable of specifically responding to an inner ear inflammation microenvironment, switching an anti-inflammatory phenotype and protecting hair cells and auditory nerves, can be used for treating noise-induced hearing loss, and can be used for preparing the HSP70-targeted chimeric antigen receptor-macrophage. The limitation that traditional hearing-aid equipment supports treatment on symptoms is broken through, and the hearing-aid device has a remarkable application prospect.

The invention discloses a metal organic framework material targeting bone marrow fat cells as well as a preparation method and application of the metal organic framework material, and belongs to the technical field of biomedical materials and tissue engineering. The material comprises: (1) a ZIF-8 core structure used for loading nucleic acid / small molecule drugs; (2) surface modification of lipid droplet targeting peptide: the lipid droplet targeting peptide is combined with a PEDF receptor to realize precise targeting; and (3) anti-miR-188 is loaded inside and is used for inhibiting adipogenic differentiation. The method at least has the following advantages: (1) a bone marrow adipocyte specific targeting MOF material is proposed for the first time, and bone metabolism intervention is converted from a mode of targeting osteoblast or macrophage to targeting adipocyte; (2) the MOF core can quickly respond to a marrow weak acid environment to realize accurate release; (3) the AdipoPep targeting peptide can obviously prolong the residence time of the bone marrow; and (4) adipogenic differentiation is significantly inhibited, osteogenesis microenvironment reconstruction is promoted, and an excellent bone mass recovery effect is shown in an osteoporosis model.

The present application relates to the technical field of biological medicine, and particularly relates to application of a nucleic acid vector encoding a macrophage monocarboxylate transporter MCT1 in preparation of a pharmaceutical composition for promoting corneal nerve regeneration and recovery of corneal sensitivity after corneal nerve injury. The present application finds that after corneal nerve injury, increasing the level of macrophage MCT1 can drive the change of the metabolic mode of macrophages to the direction of enhanced oxidative phosphorylation and reduced glycolysis, reduce the expression of local pro-inflammatory related factors, and increase the level of pro-regeneration factors and neurotrophic factors, thereby improving the regeneration of corneal nerve structure and the recovery of sensory function. Therefore, a macrophage-targeted or macrophage-biased expression vector containing a nucleic acid sequence encoding MCT1 can be used for preparation of a pharmaceutical composition for treating corneal nerve injury.

The invention discloses preparation and application of macrophage targeting nanoparticles entrapped with a cell burial function accelerant. The medicine for enhancing the intercellular function of the macrophages is a liver X receptor stimulant, and the liver X receptor stimulant comprises at least one of T0901317, GW3965, Ouabagenin and LXR-623. The surface of the targeting nanoparticle is coated with a macrophage cell membrane, and meanwhile, a urokinase type plasminogen activator receptor (uPAR) targeting ligand is modified. The nanoparticle can be efficiently accumulated at an inflammatory focus part by utilizing a macrophage cell membrane, and the modified targeting ligand is used for targeting the macrophage with damaged cell burial function, so that the cell burial function of the macrophage is enhanced, the polarization of the macrophage to an anti-inflammatory phenotype is promoted, the release of anti-inflammatory and proinflammatory cytokines is regulated, and the anti-inflammatory effect of the nanoparticle is improved. And finally, the inflammatory microenvironment of a focus part is regulated and controlled, so that a good effect of treating autoimmune diseases is achieved.

The invention relates to the technical field of biological medicine, in particular to an efficient macrophage targeting vesicle system as well as a preparation method and application thereof. The vesicle system is a chimeric vesicle (mHEs), and is prepared from extracellular vesicles (M2-EVs) derived from M2 type macrophages and apoptotic small bodies (MSC-ABs) derived from bone marrow mesenchymal stem cells. The vesicle system provided by the invention can realize specific recognition and functional regulation of macrophages, thereby playing an efficient therapeutic role in pathological processes such as tissue inflammation repair, myocardial infarction, ischemia-reperfusion injury and immune metabolism remodeling.

The invention belongs to the technical field of biological medicines, and particularly relates to application of a Tim-4 functional structural domain-based macrophage targeted nanomaterial combined intestinal selective biological preparation in inflammatory bowel diseases. Specifically, according to the macrophage targeting nano material based on the Tim-4 functional structural domain, through precise delivery of anti-inflammatory molecules and combination with a clinical drug (vializumab), dual regulation and control of innate immunity and adaptive immunity are achieved, so that the inflammatory bowel disease is efficiently treated, and therefore the macrophage targeting nano material has good practical application value.

The invention discloses a ZP3-targeting chimeric antigen receptor macrophage and application thereof, and relates to the technical field of biological medicine, the macrophage expresses a chimeric antigen receptor, and the chimeric antigen receptor comprises a signal peptide, an anti-ZP3 single-chain antibody, a hinge region, a transmembrane domain and an intracellular signal region; the anti-ZP3 single-chain antibody comprises an antibody light chain variable region, a GS linker and an antibody heavy chain variable region, the amino acid sequence of the antibody light chain variable region is as shown in SEQ ID NO: 1, and the amino acid variable region sequence of the antibody heavy chain variable region is as shown in SEQ ID NO: 2. The chimeric antigen receptor macrophage constructed based on the chimeric antigen receptor shows remarkable anti-tumor activity in vitro and in vivo, including enhanced tumor cell phagocytic ability and killing efficiency, solves the problems of insufficient target specificity, difficult cell infiltration and tumor microenvironment inhibition in liver cancer immunotherapy, and has a broad application prospect. And a treatment strategy with high targeting property, strong wettability and good safety is provided for patients with hepatocellular carcinoma.

This invention belongs to the field of biomedical technology and provides the application of exosome-derived TRIM59 inhibitors in regulating macrophage M2 polarization and combating oral squamous cell carcinoma. The TRIM59 inhibitor uses exosomes derived from oral squamous cell carcinoma tissue as carriers, with the surface modified with the M2 macrophage-targeting molecule M2pep, internally loaded with TRIM59 inhibitors and KRT6B inhibitors, and loaded with STING pathway agonists. This invention relies on the microenvironment targeting and membrane surface targeting modification of tumor-derived exosomes to precisely deliver TRIM59 inhibitors and KRT6B inhibitors to M2 macrophages and tumor cells. By silencing TRIM59, the resistance of M2 macrophages to the STING pathway is relieved, forming a temporal synergistic effect of first unlocking and then activating with the STING agonist, driving macrophages to M1 polarization.

The invention discloses a CX3CL1 targeting chimeric antigen receptor-macrophage and application thereof in treatment of GJB2 mutation related hereditary deafness, the CX3CL1 targeting chimeric antigen receptor-macrophage directly converts a CX3CL1 mediated pro-inflammatory signal into an anti-inflammatory signal, so that the macrophage is directionally polarized to an M2 type, the anti-inflammatory repair function is exerted, and the GJB2 mutation related hereditary deafness can be treated by the CX3CL1 targeting chimeric antigen receptor-macrophage. A cochlea injury microenvironment is specifically responded, anti-inflammatory repair phenotypes are switched, and cochlea epithelial cells and spiral ganglion neurons are protected; the GJB2 mutation-related hereditary deafness inner ear local inflammation can be accurately improved, apoptotic cell debris removal is promoted, the whole body immune homeostasis is not interfered, and the GJB2 mutation-related hereditary deafness inner ear local inflammation has a remarkable drug treatment application prospect.

The present disclosure relates to compositions that target tumor-associated macrophages. The compositions disclosed herein preferably comprise a glucan backbone, a tumor-associated macrophage targeting moiety, a targeting moiety linker, a payload, and optionally a payload linker. The present disclosure also provides methods for making such compositions. The present disclosure also provides treatment methods using such compositions.

The invention discloses an application of a macrophage subgroup in improving the treatment effect of AK112 (Adenosine Kinase 112). The macrophage subgroup is APOE + KRT18-CCL20-macrophages. It is found for the first time that a specific macrophage subset in a tumor microenvironment (TME) can significantly improve the AK112 double-antibody tumor killing activity, and a new target is provided for overcoming clinical drug resistance. Meanwhile, a matched flow cytometry kit is developed, the kit comprises 12 antibody combinations, and the subgroup marker is synchronously and accurately detected by a single tube through a full-spectrum flow technology. The sensitivity and the specificity are high, the AK112 treatment response can be dynamically monitored, and the disease progress can be predicted. According to the macrophage targeted synergistic mechanism and the integrated detection system, a combined treatment strategy is provided for AK112 drug-resistant patients, and a pioneering tool is provided for individualized curative effect evaluation.

The present disclosure provides methods and compositions related to the combination therapy of a macrophage-directed immunotherapy and a cytokine (e.g., IL-10). The combination of the macrophage-directed immunotherapy and a cytokine is useful in treating and / or preventing cancer (e.g., lung cancer) in a subject. Therapies that activate macrophages are emerging in cancer immunotherapy. One potential therapeutic target is the CD47-SIRPa, interaction, which acts as a myeloid immune checkpoint. Cluster of Differentiation 47 (CD47) is highly expressed on many different types of cancer cells, including lung cancer cells. CD47 binds to an inhibitory receptor, signal regulatory protein alpha (SIRPa,), that is expressed on the surface of macrophages and other myeloid immune cells.

The application discloses a chimeric antigen receptor-macrophage targeting HSP70 and application thereof in the treatment of noise-induced hearing loss, wherein the extracellular domain of the chimeric antigen receptor targeting HSP70 comprises an HSP70 specific binding fragment, and the intracellular domain comprises an IL-4 signal pathway functional element, forming a'signal switch type' CAR structure targeting HSP70, which can be used for preparing the chimeric antigen receptor-macrophage targeting HSP70 and mediating the polarization of the macrophage to M2 type and exerting the anti-inflammatory function. It has been verified that the chimeric antigen receptor-macrophage targeting HSP70 can specifically respond to the inner ear inflammatory microenvironment, switch the anti-inflammatory phenotype and protect the hair cells and auditory nerves, and can be used for treating the noise-induced hearing loss, breaking through the limitation of the symptomatic support treatment of the traditional hearing aid device and having a significant application prospect.

The invention belongs to the field of microbial technology and medicine, and particularly relates to an adhesive engineering yeast probiotic preparation as well as a preparation method and application thereof. The engineering saccharomycetes for efficiently expressing cantharides yellow is constructed by applying a synthetic biological technology. On the basis, the adhesion engineering yeast probiotics MBPSc22 are prepared through noradrenaline auto-polymerization, and the survival rate and retention capacity of the engineering yeast in gastrointestinal tracts are improved while the macrophage targeting capacity of the engineering yeast is not damaged. The adhesive engineering probiotic preparation can express canthaxanthin, directionally remove active oxygen at an inflammation part, reduce the inflammation level, increase the abundance and diversity of intestinal microorganisms, optimize the structure of the intestinal microorganisms and recover the steady state of the intestinal microorganisms, so that the aim of treating colitis is fulfilled.

The invention relates to the technical field of cell targeted therapy, in particular to a construction method of OPN-targeted chimeric antigen receptor mononuclear macrophages and application of the OPN-targeted chimeric antigen receptor mononuclear macrophages to removal of foam cells. The chimeric antigen receptor mononuclear macrophage targeting OPN is a mononuclear macrophage of which a cell membrane is integrated with a chimeric antigen receptor of which the nucleotide sequence is as shown in SEQ ID NO.7. The invention further discloses a preparation method of the chimeric antigen receptor mononuclear macrophage. Different from a technical path of only targeting membrane protein in a traditional CAR therapy, the method innovatively selects secreted protein OPN as a target spot, and realizes accurate recognition and efficient removal. The strategy breaks through the technical prejudice that secreted protein cannot be used as an effective CAR target spot, formed foam cells can be directly removed, and the lesion process is reversed. According to the technical scheme, the technical problem that a safe and effective method for removing foam cells is lacked in the prior art can be solved, and the traditional Chinese medicine composition is remarkably superior to an existing lipid-lowering or anti-inflammatory therapy and has an outstanding treatment effect and a wide clinical application prospect.

The invention relates to a DNA tetrahedral nano-element as well as a preparation method and imaging application thereof, and belongs to the technical field of biological detection. The technical problems that in the prior art, the miRNA detection sensitivity is low, traditional tetrahedral DNA is difficult to enter cells, and the living body imaging specificity is insufficient are solved. According to the invention, a nano-element composed of a tetrahedral DNA frame, a polyguanine modified chain and a catalytic hairpin chain (H1 / H2) is constructed, and cycle signal amplification of to-be-detected miRNA is realized through a chain displacement reaction; after in-vitro verification, the probe is applied to macrophage targeted detection and ARDS mouse model lung imaging. According to the invention, efficient targeting of macrophages can be realized without a transfection reagent, excellent specificity is shown in vivo and in vitro, and a reliable tool is provided for early diagnosis and mechanism research of ARDS.

The invention provides a nano motor based on rice bran protein and application of the nano motor in preparation of an anti-atherosclerosis medicine, and belongs to the technical field of biological medicine. The nano motor based on the rice bran protein is prepared by adopting a method comprising the following steps: (1) dropwise adding an ethanol solution of dihydroquercetin into a rice bran protein solution, homogenizing, performing ultrasonic treatment, centrifuging, taking precipitate, and performing freeze drying to obtain RBP-DHQ core nano particles; (2) sequentially coupling L-arginine and D-mannose on the surface of the RBP-DHQ core nano-particle to obtain a functional nano-particle; and (3) mixing the functionalized nanoparticle suspension with the spirulina dispersion liquid, and stirring to obtain the rice bran protein-based nano motor RDHQ-Arg at Man / SP. The nano motor has ROS response self-driving capability and macrophage targeting property, is free from gastrointestinal tract environment damage, and is high in oral bioavailability and outstanding in anti-atherosclerosis curative effect.

The invention relates to the field of diabetes treatment, and discloses a two-stage targeted oxidation protection nanoparticle and a preparation method and application thereof.The preparation method comprises the steps that firstly, citric acid, urea, MnCl and glutathione are dissolved in deionized water and fully stirred, and a first solution is obtained; dissolving folic acid in methanol, stirring to obtain a second solution, and mixing to obtain a precursor solution; transferring into a polytetrafluoroethylene high-pressure reaction kettle, and carrying out hydrothermal synthesis reaction; after the reaction is finished, taking out reaction liquid, performing centrifugal separation to obtain precipitate and supernate, and performing filtration, dialysis purification and freeze drying on the supernate to obtain the two-stage targeted oxidation protection nanoparticles. The problems that in the prior art, mitochondrial targeting and macrophage targeting cannot be considered at the same time, ROS cannot be effectively removed to protect mitochondrial key components, an efficient nano material system cannot promote energy generation and inhibit mitochondrial inflammation diffusion, the mitochondrial function under diabetes cannot be protected from multiple dimensions, and the mitochondrial effect cannot be affected are solved. The biological energy and the cell viability under the diabetes cannot be improved.

The application discloses a kind of self-assembled nano-preparations based on hyaluronic acid-fatty acid coupling prodrug, the self-assembled nano-preparations use hyaluronic acid-fatty acid coupling prodrug as active ingredient, the hyaluronic acid-fatty acid coupling prodrug has structure shown in formula I, wherein, R is saturated or unsaturated fatty acyl;N=1~900, m=0~899.The application also discloses the preparation method of the above-mentioned self-assembled nano-preparations, and the application of the above-mentioned self-assembled nano-preparations in preparing anti-colitis drugs.The application avoids using pharmaceutical adjuvant, can avoid the allergic reaction and toxicity caused by adjuvant, has good biocompatibility and can be biodegraded, has good clinical conversion prospect.And it can realize intestinal inflammatory site and M1 macrophage target enrichment, eliminate excess ROS while inhibiting inflammatory response, has better anti-intestinal inflammation efficacy compared with clinical 5-amino salicylic acid, dexamethasone.

This invention belongs to the interdisciplinary field of tumor immunotherapy and gene delivery, specifically relating to an aromatic hydrocarbon receptor blocking functional lipid nanoparticle, its preparation method, and its application. The ionizable lipid derived from the aromatic hydrocarbon receptor antagonist has the structure shown in formula (1): Formula (1), where x is an integer between 10 and 16, X is -N(Me)2 or -OH, and n = 0 or 1. This invention designs and synthesizes aromatic ionizable lipids that combine AHR antagonistic activity and nucleic acid delivery capability, constructing a functionalized LNP vector integrating AHR antagonism, nucleic acid delivery, and macrophage targeting. This vector can efficiently transfect macrophages in vivo and express CAR, while simultaneously blocking the AHR pathway in situ to reverse immunosuppression, enhancing antigen presentation, and activating T cell immunity. This fundamentally solves the core problem of the limited efficacy of existing CAR-M in vivo editing technology in solid tumors, especially gliomas.

The invention discloses a macrophage targeting probe, a preparation method and application, the probe is based on blood platelets coupled with a CD41 antibody, and the surfaces of the blood platelets are further modified with phospholipid compounds coupled with a cathepsin substrate peptide fragment-fluorophore structure. The probe has the advantages of good macrophage targeting property, low immunogenicity and capability of crossing a biological membrane barrier. Meanwhile, the cathepsin substrate peptide fragment-fluorophore structure in the probe can generate fluorescence only after being cut by cathepsin K in the macrophage, real-time fluorescence tracking imaging of the functional state and position of the macrophage can be effectively achieved, and then early diagnosis of diseases and guidance of disease treatment are achieved.

The application discloses an inflammation environment macrophage targeting small activating nucleic acid nano-drug, a preparation method and application thereof, and belongs to the technical field of biological medicine. The inflammation environment macrophage targeting small activating nucleic acid nano-drug is composed of a small activating nucleic acid inner core and a liposome shell. After the inflammation environment macrophage targeting small activating nucleic acid nano-drug of the application is actively targeted to an inflammation environment, the liposome shell is swollen and disintegrated after entering a cell through receptor recognition, small activating RNA is released, the expression of a gene is regulated, M1 type macrophages are reprogrammed into M2 type from two aspects of a phenotype and a metabolic mode, anti-inflammatory factors are released, and the purpose of inhibiting inflammation is achieved. Therefore, the application has a very broad application prospect in gene therapy, immunotherapy and the like of inflammation and infectious diseases.

The invention discloses a bispecific antibody targeting heterogeneous macrophages, and relates to the field of biological medicines. According to the present invention, bevacizumab is adopted as a parent antibody skeleton, antibody arms targeting CD16 are arranged on the N end side, antibody arms targeting CD163 are located on the C end side, knob mutation (K322A and T366W) is introduced into the heavy chain CH3 structural domain targeting CD16, three complementary hole mutations (T366S, L368A and Y407V) are introduced into the heavy chain CH3 structural domain targeting CD163, and cysteine residues are inserted into the S354 site of the knob chain and the Y349 site of the hole chain; variable regions (V regions) targeting CD16 and CD163 are connected in series through a (G4S) 3 flexible linker and then fused with respective constant regions (C regions). The double-antibody architecture disclosed by the invention realizes collaborative optimization in structural stability, double-antigen binding specificity, macrophage targeting and functional activity, provides an efficient and safe novel candidate drug for targeted therapy of related diseases, and has important clinical transformation value and application prospect.

Described herein are novel, macrophage targeting drug conjugates. The macrophage targeting drug conjugates comprise a drug moiety, a mannose moiety, and a linker connecting the drug moiety and the mannose moiety. The linker may comprise a hydrazone group or an oxime group.