Platelet Membrane-Camouflaged Silver Metal-Organic Framework Biomimetic Nanoparticles for the Treatment of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is characterized by high malignancy and limited treatment options. Given the pressing need for more effective treatments for TNBC, this study aimed to develop platelet membrane (PM)-camouflaged silver metal-organic framework nanoparticles (PM@MOF-Ag NPs), a biomimetic nanodrug. PM@MOF-Ag NP construction involved the utilization of 2-methylimidazole and silver nitrate to prepare silver metal-organic framework (MOF-Ag) NPs. The PM@MOF-Ag NPs, due to their camouflage, possess excellent blood compatibility, immune escape ability, and a strong affinity for 4T1 tumor cells. This enhances their circulation time in vivo and promotes the aggregation of PM@MOF-Ag NPs at the 4T1 tumor site. Importantly, PM@MOF-Ag NPs demonstrated promising antitumor activity in vitro and in vivo. We further revealed that PM@MOF-Ag NPs induced tumor cell death by overproducing reactive oxygen species and promoting cell apoptosis. Moreover, PM@MOF-Ag NPs enhanced apoptosis by upregulating the ratios of Bax/Bcl-2 and cleaved caspase3/pro-caspase3. Notably, PM@MOF-Ag NPs exhibited no significant organ toxicity, whereas the administration of MOF-Ag NPs resulted in liver inflammation compared to the control group.

A combination of a TLR7/8 agonist and an epigenetic inhibitor suppresses triple-negative breast cancer through triggering anti-tumor immune.

BACKGROUND: Combination therapy involving immune checkpoint blockade (ICB) and other drugs is a potential strategy for converting immune-cold tumors into immune-hot tumors to benefit from immunotherapy. To achieve drug synergy, we developed a homologous cancer cell membrane vesicle (CM)-coated metal-organic framework (MOF) nanodelivery platform for the codelivery of a TLR7/8 agonist with an epigenetic inhibitor. METHODS: A novel biomimetic codelivery system (MCM@UN) was constructed by MOF nanoparticles UiO-66 loading with a bromodomain-containing protein 4 (BRD4) inhibitor and then coated with the membrane vesicles of homologous cancer cells that embedding the 18 C lipid tail of 3M-052 (M). The antitumor immune ability and tumor suppressive effect of MCM@UN were evaluated in a mouse model of triple-negative breast cancer (TNBC) and in vitro. The tumor immune microenvironment was analyzed by multicolor immunofluorescence staining. RESULTS: In vitro and in vivo data showed that MCM@UN specifically targeted to TNBC cells and was superior to the free drug in terms of tumor growth inhibition and antitumor immune activity. In terms of mechanism, MCM@UN blocked BRD4 and PD-L1 to prompt dying tumor cells to disintegrate and expose tumor antigens. The disintegrated tumor cells released damage-associated molecular patterns (DAMPs), recruited dendritic cells (DCs) to efficiently activate CD8+ T cells to mediate effective and long-lasting antitumor immunity. In addition, TLR7/8 agonist on MCM@UN enhanced lymphocytes infiltration and immunogenic cell death and decreased regulatory T-cells (Tregs). On clinical specimens, we found that mature DCs infiltrating tumor tissues of TNBC patients were negatively correlated with the expression of BRD4, which was consistent with the result in animal model. CONCLUSION: MCM@UN specifically targeted to TNBC cells and remodeled tumor immune microenvironment to inhibit malignant behaviors of TNBC.

Platelet membrane-camouflaged silver metal-organic framework drug system against infections caused by methicillin-resistant Staphylococcus aureus.

BACKGROUND: Due to the intelligent survival strategy and self-preservation of methicillin-resistant Staphylococcus aureus (MRSA), many antibiotics are ineffective in treating MRSA infections. Nano-drug delivery systems have emerged as a new method to overcome this barrier. The aim of this study was to construct a novel nano-drug delivery system for the treatment of MRSA infection, and to evaluate the therapeutic effect and biotoxicity of this system. We prepared a nano silver metal-organic framework using 2-methylimidazole as ligand and silver nitrate as ion provider. Vancomycin (Vanc) was loaded with Ag-MOF, and nano-sized platelet vesicles were prepared to encapsulate Ag-MOF-Vanc, thus forming the novel platelet membrane-camouflaged nanoparticles PLT@Ag-MOF-Vanc. RESULTS: The synthesized Ag-MOF particles had uniform size and shape of radiating corona. The mean nanoparticle size and zeta potential of PLT@Ag-MOF-Vanc were 148 nm and - 25.6 mV, respectively. The encapsulation efficiency (EE) and loading efficiency (LE) of vancomycin were 81.0 and 64.7 %, respectively. PLT@Ag-MOF-Vanc was shown to be a pH-responsive nano-drug delivery system with good biocompatibility. Ag-MOF had a good inhibitory effect on the growth of three common clinical strains (Escherichia coli, Pseudomonas aeruginosa, and S. aureus). PLT@Ag-MOF-Vanc showed better antibacterial activity against common clinical strains in vitro than free vancomycin. PLT@Ag-MOF-Vanc killed MRSA through multiple approaches, including interfering with the metabolism of bacteria, catalyzing reactive oxygen species production, destroying the integrity of cell membrane, and inhibiting biofilm formation. Due to the encapsulation of the platelet membrane, PLT@Ag-MOF-Vanc can bind to the surface of the MRSA bacteria and the sites of MRSA infection. PLT@Ag-MOF-Vanc had a good anti-infective effect in mouse MRSA pneumonia model, which was significantly superior to free vancomycin, and has no obvious toxicity. CONCLUSIONS: PLT@Ag-MOF-Vanc is a novel effective targeted drug delivery system, which is expected to be used safely in anti-infective therapy of MRSA.

Synovial chondromatosis of the hip joint in childhood: A case report and literature review.

RATIONALE: Pain in the hip joint is a common symptom in children. The common diseases leading to pain in the hip joint in children include transient synovitis of the hip, septic arthritis of the hip, and Legg-Calve-Perthes disease. PATIENT CONCERNS: A 7-year-old boy was admitted due to pain in the right hip joint and limping for more than 1 month. DIAGNOSIS: Synovial chondromatosis. INTERVENTIONS: The patient underwent a hip open surgery, all the loose bodies in articular capsule were removed. OUTCOMES: At the 6-month follow-up, pain and limping disappeared, and the range of activity of the hip joint was restored to a normal level. CONCLUSIONS: Synovial chondromatosis is an uncommon disease which can cause pain of hip joint in children. LESSONS: When the pediatric orthopedic surgeon treats the children suffered with hip pain the surgeon should be aware of this rare disease.

Meropenem-induced immune thrombocytopenia and the diagnostic process of laboratory testing.

BACKGROUND: Drug-induced immune thrombocytopenia (DITP) is a serious, life-threatening clinical syndrome, the diagnosis of which is consistently difficult. In this report, we present a case of DITP caused by meropenem that was confirmed by laboratory tests. CASE REPORT: A 59-year-old male patient developed severe thrombocytopenia 8 days after the administration of meropenem and cefoperazone-sulbactam. After other causes were ruled out, DITP was suspected. Drug-induced platelet (PLT) antibodies were detected by enzyme immunoassay, flow cytometry, and monoclonal antibody immobilization of PLT antigens (MAIPA). All these tests were performed in the presence and absence of the associated drugs. RESULTS: PLT antibodies were detected in the patient's serum only in the presence of meropenem. MAIPA experiments demonstrated that glycoprotein IIb/IIIa was the binding site of the meropenem-induced PLT antibodies. CONCLUSIONS: Drug-induced immune thrombocytopenia should be considered in cases of acute thrombocytopenia in patients undergoing meropenem treatment. Clinicians should be cognizant of DITP, and a definitive diagnosis should be pursued, if feasible.