作者單位：南方醫(yī)科大學(xué)基礎(chǔ)醫(yī)學(xué)院腫瘤研究所

摘要：The immunosuppressive tumor microenvironment (TME) severely limits the clinical applications of cancer immunotherapy. Herein, a hypoxia-responsive delivery system is constructed simply by coordinating ferric(Fe³⁺) with mitoxantrone (MTO), sulfasalazine (SAS), and hypoxia-sensitive dopamine derivative of polyethylene glycol (PEG) using “one-pot" reaction for the “closed-loop" synergistic enhancement of ferroptosis and immunotherapy. Hypoxia-sensitive PEG ensures the integrity of delivery system in circulation to prevent the premature leakage of drugs, and the detachment of PEG in the interior hypoxic TME can facilitate the deep penetration and the subsequent tumor uptake. The released iron and MTO induce the generation of reactive oxygen species (ROS), while SAS inhibits the elimination of lipid peroxides by inhibiting SLC7A11 subunit of glutamate-cystine antiporter, which synergistically induces immunogenic ferroptosis to promote dendritic cells maturation and T cells activation. The activated CD⁸⁺ T cells then release interferon γ (IFN-γ) and in turn enhance ferroptosis by downregulating the expression of SLC7A11. As a result, the “closed-loop" synergistic enhancement between ferroptosis and immunotherapy significantly prevents tumor growth and prolonged survival time of tumor-bearing mice with no obvious systemic toxicity. The excellent therapeutic effect together with the scalable synthesis and controllable quality will promise its translation to clinic as a novel immunotherapy.

Anti-FAPA/AF647 pAb | FCM

作者單位：韓國高等科學(xué)技術(shù)研究所(KAIST)KAIST生物科學(xué)系

文獻引用抗體：bs-0283P-FITC

OVA / FITC

作者單位：中國科學(xué)院理化技術(shù)研究所低溫生物醫(yī)學(xué)工程北京重點實驗室和低溫學(xué)重點實驗室液態(tài)金屬與低溫生物醫(yī)學(xué)研究中心

摘要：Therapeutic cancer vaccines have been vigorously sought to bolster host adaptive immunity against metastatic cancers, but tumor heterogeneity, ineffective antigen utilization, and immunosuppressive tumor microenvironment hinder their clinical applications. Autologous antigen adsorbability and stimulus-release carrier coupling with immunoadjuvant capacity are urgent for personalized cancer vaccines. Here, we propose a perspective strategy of using a multipotent gallium-based liquid metal (LM) nanoplatform for personalized in situ cancer vaccines (ISCVs). The antigen-capturing and immunostimulatory LM nanoplatform can not only effectively destroy orthotopic tumors to generate multifarious autologous antigens upon external energy stimulation (photothermal/photodynamic effect) but also capture and transport antigens into dendritic cells (DCs) to enhance antigen utilization (adequate DCs uptake, antigen-endo/lysosomal escape) and facilitate DCs activation (mimic alum immunoadjuvant capacity), which ultimately awaken systemic antitumor immunity (expand cytotoxic T lymphocytes and modulate tumor microenvironment). With immune checkpoint blockade (anti-PD-L1) to further relieve the immunosuppressive tumor microenvironment, the positive tumoricidal immunity feedback loop was established to effectively eliminate orthotopic tumors, inhibit abscopal tumor growth, relapse, and metastasis as well as tumor-specific prevention. Collectively, this study demonstrates the potential of a multipotent LM nanoplatform for personalized ISCVs, which will open frontier exploration of LM-based immunostimulatory biomaterials and may encourage further investigation of precise individualized immunotherapy.

文獻引用抗體：bs-10947R

Anti-Bradykinin pAb / HRP

摘要：An important role for liver in the regulation of adipose tissue thermogenesis upon cold exposure has been suggested; however, the underlying mechanisms remain incompletely defined. Here, we identify elevated serum bradykinin levels in response to acute cold exposure in male mice. A bolus of anti-bradykinin antibodies reduces body temperature during acute cold exposure, whereas bradykinin has the opposite effect. We demonstrate that bradykinin induces brown adipose tissue thermogenesis and white adipose tissue browning, and bradykinin increases uncoupling protein 1 (UCP1) expression in adipose tissue. The bradykinin B2 receptor (B2R), adrenergic signaling and nitric oxide signaling are involved in regulating bradykinin-increased UCP1 expression. Moreover, acute cold exposure inhibits hepatic prolyl endopeptidase (PREP) activity, causing reduced liver bradykinin degradation and increased serum bradykinin levels. Finally, by blocking the breakdown of bradykinin, angiotensin-converting enzyme inhibitors (ACEIs) increase serum bradykinin levels and induce brown adipose tissue thermogenesis and white adipose tissue browning via B2R. Collectively, our data provide new insights into the mechanisms underlying organ crosstalk in whole-body physiology control during cold exposure and also suggest bradykinin as a possible anti-obesity target.