67 results about "Immunogenic cell death" patented technology

The invention relates to the technical field of hepatocellular carcinoma, in particular to a hepatocellular carcinoma prognosis model construction method based on immunogen cell death related genes and application, and an accurate prognosis prediction model is constructed by integrating the immunogen cell death related genes (IRGs) and molecular characteristics of hepatocellular carcinoma. A training set and a verification set provided by TCGA and ICGC databases are utilized, so that the model can perform effective sample analysis under a large-scale data background. Through consistency clustering analysis, the optimal clustering number is determined, the samples are orderly divided into different molecular subtypes, and it is ensured that the samples in each subtype have similar molecular characteristics. According to the invention, the capability of capturing liver cancer heterogeneity on the molecular level of the model is increased, so that the accuracy of prognosis prediction is improved.

The invention discloses an aptamer-modified lipid nano delivery platform as well as a preparation method and application thereof, and belongs to the field of biomedicine. The platform is prepared by taking DPPC, DOTAP and cholesterol as basic lipid components, Ce6 as a sound-sensitive agent and Flt3L as an immune agonist, controlling the particle size through gradient extrusion, and coupling cholesterol with an EpCAM aptamer for surface modification. The method has the core advantages that active targeting enrichment of tumors is realized by virtue of the aptamer, tumor cell immunogen cell death (ICD) is induced in combination with a sonodynamic therapy (SDT), and damage-related molecular patterns (DAMPs) are released; meanwhile, Flt3L is released in a tumor microenvironment, collection and activation of type 1 classical dendritic cells (cDC1) are specifically promoted, an'endogenous cDC1 vaccine 'is constructed, and CD8 + T cell mediated anti-tumor immune response is enhanced. Experiments prove that the platform can significantly improve the cDC1 infiltration level of a tumor site, effectively inhibit the progress of prostate cancer (PCa), and provide a new normal form for immune'cold tumor 'treatment.

The invention discloses a platinum (IV)-pirfenidone compound prodrug, a preparation method and microenvironment remodeling anti-tumor application, and belongs to the field of medical technology and drug synthesis. A series of molecules are characterized by being platinum prodrugs modified by pirfenidone derivatives. The synthesis method sequentially comprises the following steps: oxidizing platinum drugs, modifying hydroxyl groups, and introducing pirfenidone derivatives through esterification reaction. A series of molecules are reduced into Pt (II) drugs at the focus to kill cancer cells, and meanwhile, the released pirfenidone derivative can remodel the tumor microenvironment. The platinum prodrug disclosed by the invention not only has excellent cancer cell killing ability, but also is relatively low in drug resistance and excellent in safety, can trigger immunogenic cell death, and is a brand new chemotherapy-immunotherapy method. A series of molecules are convenient to synthesize, the preparation process is simple, and the amphipathicity is excellent, the anti-cancer capability is excellent, the drug resistance and toxicity are low, and the clinical application prospect is good.

The application belongs to the technical field of polymer medicine synthesis, and particularly relates to a polymer for inducing tumor immunogenic cell death, a preparation method and application. The polymer for inducing tumor immunogenic cell death provided by the application has a structure as shown in formula I: in formula I, m is an integer of 110-120; n is an integer of 70-75; p is an integer of 21-79; and R is one of a tertiary amine group, a sulfide group and a tertiary amine sulfide group. The polymer provided by the application has pH responsiveness, can be self-assembled to obtain a polymer nanovesicle, can load drugs, can induce tumor immunogenic cell death (ICD) after application to form an in-situ tumor vaccine, can realize controllable release of a hydrophobic immunoadjuvant, can polarize tumor-associated macrophages (TAMs), and is suitable for tumor immunotherapy application.

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 invention belongs to the technical field of biological medicines, and particularly discloses a pH and ultrasound double-response type oncolytic microorganism as well as a preparation method and application thereof. On the basis of a tumor targeting platform, a mild thermal response gene loop expression GM-CSF and a surface-coated oncolytic microbial system are integrated, chemotherapeutic drugs are released in a tumor core area, and immunogenic cell death is induced. A thermal response loop is accurately activated through low-intensity focused ultrasound, and engineering bacteria are promoted to express GM-CSF and secrete a large amount of mannose modified OMVs. Due to the nanometer size and mannose targeting of the OMVs, the OMVs are efficiently enriched in lymph nodes, the OMVs are reprogrammed into an immune activation state from an immune tolerance state, and the OMVs and ICD cooperate to promote dendritic cell maturation, tumor antigen presentation and activation of tumor killer T cells, so that a remarkable and powerful treatment effect is achieved in various tumor models, and the application prospect is wide. A new strategy is provided for remodeling the lymph node immune microenvironment and enhancing the anti-tumor immune response.

The invention discloses a nano-particle for inducing death of tumor immunogen cells, a preparation method and application. The preparation method of the nano-particles comprises the following steps: taking a BiOCl nanosheet as a carrier, enabling CeO2 to generate and crystallize in situ on the surface of the BiOCl nanosheet, and forming a BiOC / CeO2 heterojunction; the method comprises the following steps: carrying out a dehydration reaction on NH2-PEG2000-NH2 and DL lipoic acid to synthesize NH2-PEG2000-TA; the preparation method comprises the following steps: reacting NH2-PEG (Polyethylene Glycol) 2000-TA with a Pardaxin peptide of which the carboxyl is activated, so as to generate Pardaxin-PEG 2000-TA; the preparation method comprises the following steps of: coupling Pardaxin-PEG2000-TA (Polyethylene Glycol 2000-TA) and a BiOC / CeO2 heterojunction; the PBCP nanoparticles obtained by the preparation method promote the yield of active oxygen in the endoplasmic reticulum of tumor cells to be increased sharply, so that the endoplasmic reticulum stress is effectively excited, tumor immunogenic cells are induced to die, and the anti-tumor effect is achieved. The nanoparticle can be combined with the existing PD-1 / PD-L1 inhibitor for use, and shows a better anti-tumor effect than the single use of the PD-1 / PD-L1 inhibitor.

This invention relates to the fields of brachytherapy and radiosensitization, specifically providing a... 125 I-nano implantable particles, their preparation methods, and applications. 125 The 1-nanometer implanted particles have a core-shell structure, consisting of a particle core and particles adsorbed on the outer surface of the particle core. 125 I and the particles encapsulated in the nucleus and 125 The outer shell of the I-type photosensitizer is a covalent organic framework. This invention... 125 The core of the I-nanometer implanted particle is used to enhance the energy deposition of gamma rays and X-rays, generating more hydroxyl radicals; the shell containing a type I photosensitizer is used to absorb the energy of Auger electrons and internal conversion electrons and excite the photosensitizer to generate singlet oxygen, effectively improving the response to... 125 The efficiency of I decay energy utilization. 125 I-nano implanted particles, combined with internal radiation therapy and radiodynamic therapy, destroy tumor cell DNA and cell membranes, enhance tumor killing and induce immunogenic cell death, thereby activating anti-tumor immunity and inducing remote effects.

The present application belongs to the technical field of coordination chemistry and biomedical science, and provides a multifunctional iridium (III) complex, a preparation method and application thereof. The multifunctional iridium (III) complex (Mito-Ir) is composed of an iridium (III) complex cation and a coordination anion shown in the following formula. Mito-Ir can efficiently target mitochondria, and also has the abilities of phosphorescence imaging, type I and type II active oxygen generation, and photocatalytic oxidation of nicotinamide adenine dinucleotide. Under light irradiation, Mito-Ir triggers severe mitochondrial dysfunction through the above synergistic effect, and then specifically activates the caspase-3 / GSDME signaling pathway, and significantly induces pyroptosis; this pyroptosis-based cell death mechanism can effectively overcome the apoptosis tolerance of tumor cells, and is accompanied by the release of a large amount of inflammatory factors and damage-associated molecular patterns, stimulates immunogenic cell death, and activates the body's anti-tumor immune response.

The application discloses a kind of SNPs loaded engineered escherichia coli dual-response delivery systems and its preparation method and application, the preparation method includes the engineered escherichia coli of overexpressing Flt3L and TIM-3 scFv is co-incubated with NHS-PEG-CHO, obtain aldehyde functionalized escherichia coli;After activation SNPs is reacted with TFA-hydrazine, obtain hydrazine functionalized SNPs;Aldehyde functionalized escherichia coli and hydrazine functionalized SNPs are reacted;The delivery system of the application can rely on SNPs under laser stimulation Photo-thermal effect, photodynamic effect and generate a large number of ROS, efficiently induce tumor cells to occur immunogenic cell death (ICD), and by overexpressing Flt3L and TIM-3 scFv, activate DC cell and block TIM-3 path, restore DC, T cell function, realize the efficient synergy of photodynamic therapy+photothermal therapy+immunotherapy, and then reach the effective treatment of colorectal cancer.

This invention discloses a photoactivated nanoparticle-based drug delivery material for immunoadjuvants, its preparation method, and its applications. The drug delivery material is constructed from photosensitizer monomers, crosslinking monomers, and immunoadjuvant prodrug monomers within a confined space of a nanoemulsion via a copper-free click polymerization reaction to form crosslinked polymer nanoparticles. The nanoparticle size is controllable, and the composition is precisely defined. Under physiological conditions, the drug delivery material exhibits good colloidal stability and high drug loading. Upon near-infrared light irradiation, the generated ROS can cleave the thioketone bonds, causing the nanoparticles to depolymerize and achieving photo-triggered, controllable release of the immunoadjuvant. Under photodynamic action, this drug delivery material efficiently generates reactive oxygen species to induce immunogenic cell death in tumor cells. Simultaneously, the released immunoadjuvant activates the TLR7 / 8 pathway, promotes dendritic cell maturation, and enhances the systemic anti-tumor immune response, thereby inhibiting the growth of tumors in situ and at distant sites, and reducing the risk of metastasis and recurrence.

The invention provides a method for preparing calcium-based nano particles by a reversed-phase microemulsion method, an organic calcium salt nano material and application of the organic calcium salt nano material as a nano drug, and belongs to the field of biomedical nano materials. The calcium-based nanoparticles can be formed by reacting calcium dodecyl benzene sulfonate with ammonium salt of corresponding ions or a hydroxyl-containing organic matter aqueous solution; the preparation method of the calcium-based nanoparticles has certain universality, and nano-material drugs including calcium succinate, calcium hypophosphite, calcium gluconate, calcium formate, calcium citrate and the like are successfully synthesized. The synthesis method is simple, mild in reaction condition, environment-friendly, high in repeatability, capable of realizing batch preparation and low in raw material cost. When the calcium salt nano-drug such as calcium succinate enters tumor cells through endocytosis, a large number of ions are brought into the cells, and suddenly excessive ions can cause osmotic pressure and homeostasis imbalance in the cells, activate a pyroptosis pathway of the cells and induce death of immunogenic cells.

The invention belongs to the technical field of biological medicine, and provides an iron-based nanodot capable of guiding MRI and delivering medicine and a preparation method and application of the iron-based nanodot. The iron-based nanodot is used as a chemotherapeutic drug carrier, and is prepared from a cell protective agent amifostine (AT) and key nutritional metal iron ions (Fe < 3 + >) for inducing ferroptosis through a supramolecular self-assembly technology. The iron-based nanodot can efficiently load the chemotherapeutic drug, improves pharmacokinetic behaviors such as short in-vivo circulation period and fast metabolism of the chemotherapeutic drug, accurately delivers the chemotherapeutic drug to a tumor site, and improves the drug effect of the chemotherapeutic drug; in addition, the iron-based nanodots can realize efficient ferroptosis treatment under the guidance of MRI to induce immunogenic cell death and inhibit growth, metastasis and diffusion of tumor cells.

The invention relates to the technical field of biological medicines, and particularly discloses a nanocapsule SMCPM and application thereof in medicines for treating or preventing osteosarcoma and pulmonary metastasis. The SMCPM is composed of a photosensitizer Ce6 carried by mesoporous silicon oxide-manganese oxide particles, an NRF2 inhibitor ML385 and an OS targeting peptide PT-7. Experiments prove that the SMCPM is high in penetrating power and strong in cell killing effect; by down-regulating NRF2 expression and reversing nuclear translocation, a biochemical inhibitory microenvironment can be effectively repaired, the tolerance of cells to active oxygen and epithelial-mesenchymal transition activated and induced by a NOTCH1 signal axis are remarkably reduced, the oxidative stress level of the cells is enhanced, and PIT-induced immunogenic cell death is promoted; the released Mn < 2 + > and double-stranded DNA can regulate and control an immunosuppressive microenvironment by activating an STING pathway in cells, thereby inhibiting the growth of osteosarcoma and preventing lung metastasis.

This invention belongs to the field of biomedical technology, specifically disclosing a nanomicelle FluDox-MIC, its preparation method, and its uses. This nanomicelle is formed by the self-assembly of flumatinib and doxorubicin co-loaded in mPEG-DSPE, exhibiting pH-responsive release properties. Upon entering the tumor microenvironment, it releases the drug. The released flumatinib induces the degradation of the poliovirus receptor (PVR / CD155), relieving its inhibitory signal on NK cells and reactivating innate immune surveillance. Simultaneously, low-dose doxorubicin induces significant immunogenic cell death (ICD), initiating and amplifying tumor-specific T cell-mediated adaptive immunity. Through the synergistic activation of innate and adaptive immunity, the nanomicelle of this invention can effectively inhibit melanoma growth and overcome immunotherapy resistance, showing promising clinical application prospects.

The invention relates to the technical field of medical treatment, in particular to a preparation method of injectable BiOCl (at) CuOF127 (at) rGO thermosensitive hydrogel for superficial tumor treatment, which comprises the following steps: pretreating raw materials, preparing BiOCl nanosheets by a solvothermal method, washing and drying for later use; according to the manufacturing method of the injectable BiOCl (at) CuOF127 (at) rGO thermosensitive hydrogel for superficial tumor treatment, the injectable BiOCl (at) CuOF127 (at) rGO thermosensitive hydrogel is embedded into injectable, conductive and thermosensitive hydrogel composed of PluronicF127 (F127) and reduced graphene oxide (rGO), the injectable BiOCl (at) CuOF127 (at) rGO thermosensitive hydrogel is used for combined treatment of breast cancer, remarkable ROS outbreak and effective breast cancer cell ablation are induced through in-vitro and synergistic therapy, toxicity to normal cells is minimum, and the injectable BiOCl (at) CuOF127 (at) rGO thermosensitive hydrogel can be applied to in-vivo and in-vivo treatment of breast cancer. In-situ breast tumors treated with US + NIR show obvious fading, proliferation and angiogenesis reduction, apoptosis and immunogen cell death pathway activation and good biocompatibility, an accurate and minimally invasive strategy is established, piezoelectric catalysis and photo-thermal conversion are combined, and the in-situ breast tumors are used for effective breast cancer treatment.

This invention discloses a nanoparticle-based drug delivery system, MPL@ICC, its synthesis method, and its applications. The MPL@ICC system consists of hollow, porous nano-MnO2, a hydrophilic targeting complex on its surface, and an acid-responsive drug, INH-CA, and a photosensitizer loaded internally. It possesses both targeted transport and controlled release capabilities against human hepatocellular carcinoma cells (HepG2), allowing it to accumulate within these cells and achieve photodynamic therapy (PDT) and free radical-induced immune killing within the tumor. Simultaneously, it directly kills tumor cells and transforms them from non-immunogenic to immunogenic, mediating an anti-tumor immune response and achieving immunogenic cell death (ICD). This overcomes the shortcomings of ICD-induced cancer treatment strategies, which often fail to produce strong and durable therapeutic effects, and does not induce normal cell apoptosis, thus possessing controllability, effectiveness, and safety.

The invention relates to a thermo-sensitive hydrogel drug sustained-release stent for jointly loading a hypotensive drug and a chemical / immunotherapy drug, which is prepared from a thermo-sensitive material and loads three drug components, namely losartan, oxaliplatin and an immune checkpoint inhibitor. The temperature-sensitive hydrogel can form gel in situ under the triggering of body temperature, and meanwhile, the acting time of the medicine on a target part is prolonged. The antihypertensive drug losartan potassium can reduce tumor interstitial substances, reduce tumor solid stress, relieve vascular compression in tumors and improve tumor hypoxia. Meanwhile, the chemotherapeutic drug oxaliplatin can induce tumor immunogenic cell death, and the tumor immunosuppressive microenvironment is effectively relieved. The immune checkpoint inhibitor can be used for accurately blocking the combination of the PD-L1 and the PD-1 and activating the T cell mediated anti-tumor immune response. According to the present invention, the potent anti-tumor immune response can be triggered, the excellent tumor inhibition effect can be achieved, the strong far-end effect can be even induced, and the growth of the far-end tumor can be effectively inhibited.

The invention discloses a multifunctional nano delivery system for tumor collaborative treatment. The system is based on double-targeting temperature-sensitive lipidosome, the skeleton of the system is composed of temperature-sensitive lipidosome, cholesterol and the like, and the surface of the system is modified with ginsenoside and an AS1411 aptamer so as to realize targeted delivery of tumors. A CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-associated 9) system targeting LDH (layered double hydroxides), a photo-thermal agent IR-1048 and a phase change agent PFP (polyfluoropropylene) are co- Under the irradiation of near-infrared light, the phase change of the PFP is triggered by the IR-1048 mediated photothermal effect, so that the controllable release of the therapeutic drug is realized. According to the released CRISPR-Cas9 system, an immunosuppressive microenvironment is remodeled by editing an LDHA gene, and the CRISPR-Cas9 system cooperates with immunogen cell death (ICD) induced by photothermal therapy to jointly enhance anti-tumor immune response. In-vivo and in-vitro experiments show that the nanoparticles realize efficient tumor collaborative treatment through dual effects of local physical ablation and metabolism intervention and whole body immune activation. The research provides a potential technical platform for developing a new generation of tumor precise immunotherapy strategy.

The application discloses an MMP-2 responsive targeted brain glioma synergistic diagnosis and treatment and immune activation nano probe and a preparation method and application thereof, and relates to the technical field of biological medicine. The probe is formed by assembling an Angiopep-2 targeting peptide, an MMP-2 response sequence, a chemotherapeutic drug and a photosensitizer I-BODIPY, has a hydrodynamic diameter of 10-50 nm, and has excellent biocompatibility. The probe is combined with an LRP1 receptor through the Angiopep-2 to cross the blood-brain barrier, is specifically cut by MMP-2 in a tumor microenvironment to release drugs at a fixed point, integrates the functions of chemotherapy, photothermal / photodynamic therapy and fluorescence imaging, synchronously activates immunogenic cell death and paraptosis, and reshapes an anti-tumor immune microenvironment. The probe can realize precise targeting of brain glioma, synergistic diagnosis and treatment, immune activation and tumor staging evaluation, significantly prolongs the survival period of tumor-bearing mice, and provides a new scheme for glioblastoma diagnosis and treatment.

The application belongs to the field of new adjuvants and new dosage forms of pharmaceutical preparations, and particularly relates to a type I and type II immunogenic cell death inducer ion pairing engineered nanoassemblies as well as construction and application thereof. The nanoassemblies are composed of type I ICD inducers, type II ICD inducers, hydrophobic auxiliary counterions and amphiphilic lipid ion pairing. The type I ICD inducer is selected from mitoxantrone, doxorubicin, oxaliplatin or cyclophosphamide; the type II ICD inducer is selected from hypericin; and the hydrophobic auxiliary counterion is selected from cholesteryl sodium sulfate, cholic acid, deoxycholic acid, chenodeoxycholic acid, lithocholic acid, glycolcholic acid, taurocholic acid, glycochenodeoxycholic acid, taurochenodeoxycholic acid, deoxycholic acid lysine derivative, oleanolic acid and ursolic acid. The type I and type II ICD inducers are combined in the application, and have a synergistic tumor treatment effect.

The invention belongs to the technical field of nano biomedicine, and particularly discloses a preparation method of a galangin-loaded bionic nano dendritic cell (DCs) vaccine and application of the galangin-loaded bionic nano dendritic cell (DCs) vaccine in ovarian cancer treatment. The inner core of the vaccine is galangin (GA)-loaded polylactic acid-glycolic acid copolymer (PLGA) nanoparticles, and the shell of the vaccine is formed by coating a DCs film carrying tumor antigens. The nano DC vaccine retains the antigen presentation function of natural DCs, and the GA loaded on the nano DC vaccine can induce tumor cells to generate immunogenic cell death. By means of the design, the vaccine can efficiently load specific tumor-associated antigens, and the homing capacity of the vaccine to lymph nodes and tumor microenvironments is remarkably enhanced. Experiments show that GA-NPs (at) DCV is used for treating subcutaneous tumor and in-situ ovarian cancer mouse models.

The invention relates to a proportion-locked in-situ gel for tumor chemoimmunotherapy as well as a preparation method and application of the proportion-locked in-situ gel. The in-situ gel comprises a pharmaceutical composition and sodium alginate (ALG), wherein the pharmaceutical composition is composed of gemcitabine (GEM), oxaliplatin (OXA) and cytidine deaminase inhibitor chidauridine (CDZ), and the sodium alginate (ALG) is used as a carrier. The in-situ gel is subjected to intratumor injection and then gelation is triggered by Ca < 2 + > in a tumor, so that local retention and synchronous slow release of the medicine are realized. Metabolic inactivation of GEM is inhibited through CDZ, the optimal treatment proportion of GEM and OXA is maintained at the tumor site, and meanwhile the in-situ gel solves the problems of systemic toxicity and proportion imbalance caused by traditional intravenous administration. The synergistic effect of the pharmaceutical composition not only enhances direct cytotoxicity, but also synergistically activates anti-tumor immune response through OXA-induced immunogenic cell death and GEM-mediated regulatory T cell depletion. The invention realizes safe and efficient local chemical immunotherapy, and has a good clinical application prospect.

This paper describes a class of dyes containing 1,4-diazabicyclo[2.2.2]octane, their preparation methods, and applications, belonging to the fields of optical diagnostics and biomedicine. The dye comprises the dye molecule and 1,4-diazabicyclo[2.2.2]octane covalently coupled to the dye. 1,4-diazabicyclo[2.2.2]octane directly quenches singlet oxygen generated by the dye, affecting the triplet state of the dye, thereby improving its anti-bleaching ability and photostability, and reducing phototoxicity during fluorescence imaging. Furthermore, the introduction of 1,4-diazabicyclo[2.2.2]octane significantly improves the brightness of the dye, inhibits photoscintillation, and enhances its water solubility. Its protonation characteristic enhances the dye's mitochondrial targeting ability. These compounds, by reducing singlet oxygen and enhancing the local photothermal and reactive oxygen species production in mitochondria, induce potent cell necrosis, apoptosis, and immunogenic cell death, comprehensively improving anticancer efficacy. These compounds exhibit excellent photostability and low skin toxicity, showing broad application prospects.

The invention provides a nano preparation co-loaded with olaparib and a cell nucleus targeting photosensitizer as well as a preparation method and application of the nano preparation. The nano preparation is composed of a lipid bilayer membrane, wherein the lipid bilayer membrane is composed of DPPC (Diphenyl Phosphate Polycarbonate), DSPE-PEG2000, DSPE-PEG2000-RGD (Reduced Glutamic Acid), cholesterol, olaparib and a nuclear targeting photosensitizer. The nuclear targeting photosensitizer is obtained by covalent coupling of pyropheophorbide a and a cell nucleus targeting group. The preparation method comprises a film hydration-ultrasonic method. The nano preparation initiates a large amount of DNA damage, effectively induces immunogenic cell death and activates an STING pathway through a synergistic effect of a nuclear targeting photodynamic effect and DNA repair inhibition, so that an anti-tumor immune response is excited, and the nano preparation can be used for photodynamic therapy, photoimmunotherapy and sonodynamic therapy of tumors.

The invention relates to the technical field of nano biomedicine, in particular to a cyclometalated Ir (III)-AZT compound as well as a preparation method and application thereof. According to the invention, the cyclometalated Ir (III)-AZT compound is prepared and has low dark toxicity and excellent photodynamic anti-tumor activity. In a tumor acid environment, the iridium complex in the compound generates various ROS under an illumination condition through I / II type photodynamic force, the zidovudine in the compound mediates stress conduction from an endoplasmic reticulum to mitochondria, and the iridium complex and the zidovudine synergistically induce immunogenic cell death and promote tumor antigen and injury related molecular mode release at the same time. In addition, the synergistic treatment can adaptively up-regulate PD-L1 expression of tumor cells, and can further synergistically inhibit tumor growth and relieve an in-vivo immunosuppressive microenvironment when being combined with an immunosuppressor (such as PD-L1), so that a dual anti-tumor effect of'photodynamic and immune synergy 'is realized.

Disclosed are useful compositions of mixed lineage kinase domain-like (MLKL) derived fusion constructs and their methods of use in cellular depletion therapies. Embodiments of the present disclosure provide a chimeric cell death protein that induces immunogenic cell death in various types of cancers and also has applications in viral infection. The present disclosure also provides different methods of delivering the disclosed compositions or fusion constructs to a subject with cancer or tumor.

This invention discloses a method for preparing and applying a chimeric peptide nanomedicine for photodynamic immunotherapy of triple-negative breast cancer. The nanomedicine uses the functional chimeric peptide Fmoc-K(PpIX)-PLGLAG-CVRARTR as its self-assembly core and is loaded with the exosomal PD-L1 inhibitor GW4869. This chimeric peptide contains an MMP-2 responsive sequence, the photosensitizer PpIX, and the PD-L1 targeting peptide CVRARTR. It is structurally stable in the bloodstream and can specifically accumulate in tumor tissues that highly express PD-L1 via the targeting peptide. Enzymatic degradation is triggered by the highly expressed MMP-2 in the tumor microenvironment, achieving structural deformation, controlled drug release, and enhanced deep tumor penetration. This invention can simultaneously achieve a triple synergistic therapeutic effect: PDT generates reactive oxygen species that directly kill tumor cells and trigger immunogenic cell death, enhancing immunogenicity; the targeting peptide competitively blocks PD-L1 on the cell surface, relieving local immunosuppression; and the inhibitor downregulates exosomal PD-L1 secretion, inhibiting systemic immune escape. This approach effectively overcomes the bottleneck of low response rates in existing TNBC immunotherapy.

The invention belongs to the technical field of oxaliplatin hydrogel drug delivery systems, and particularly relates to an oxaliplatin prodrug hydrogel protein capture system for tumor treatment and a preparation method of the oxaliplatin prodrug hydrogel protein capture system. According to the invention, a temperature-sensitive material sulfhydrylated pluronic F127, a biological viscous material dopamine modified hyaluronic acid and a dopamine modified oxaliplatin prodrug are cross-linked to prepare a biological viscous temperature-sensitive hydrogel, and a protein capture adhesion hydrogel preparation capable of being injected in tumors is formed. According to the present invention, the oxaliplatin can be used to enhance the cancer cell killing efficiency by reducing the dispersion of oxaliplatin, enhance the immunogen cell death (ICD) effect to generate a large number of damage-related molecular patterns (DAMPs), capture the released DAMPs through the biological viscous material, prolong the retention of the tumor antigen at the focus site, continuously stimulate the in-vivo anti-tumor immune response, and provide the anti-tumor therapeutic effect on the tumor cells. The efficiency of antigen-triggered immunoreaction is improved, and the method has wide application value and prospect in anti-tumor immunity.

The application discloses a flaxseed oil body carrier for treating hepatocellular carcinoma by inducing immunogenic cell death and a preparation method and application thereof. The flaxseed oil body is obtained by a water extraction method, then curcumin is loaded on the flaxseed oil body, and then mineralization is performed to obtain the flaxseed oil body carrier for treating hepatocellular carcinoma by inducing immunogenic cell death. Through in vitro and in vivo experiments, it is proved that the carrier can effectively inhibit the growth of hepatocellular carcinoma, and the characterization results show that the carrier can further enhance the tumor killing effect by activating the immune system. Further, after the anti-PD-L1 is combined with the carrier, a synergistic effect can be produced, the treatment effect of the alpha PD-L1 immunotherapy on the anti-HCC lung metastasis is enhanced, and it is proved that the carrier can be used for combining the alpha PD-L1 immunotherapy to enhance the anti-tumor effect, and has a wide application prospect.