100 research outputs found
Performance Improvement on Double-Pass Parallel-Plate Mass Exchangers under Asymmetric Uniform Wall Concentrations
No full text本書目待補正國際20101005~2010100
Local Delivery of Molecular Hydrogen by Fluorinated Zeolitic Imidazole Framework Nanosheets Boosts Cancer Immunotherapy
No full textIdentifying strategies to improve the efficacy of the immune checkpoint blockade (ICB) remains a major clinical need. Based on the high tissue penetration capability of hydrogen molecules (H₂) and their immunomodulatory effects, this work proposes a local gas delivery strategy targeting the tumor microenvironment for high-efficacy hydrogen immunotherapy. We synthesized hepta-fluorinated zeolitic imidazolate frameworks nanosheet (F₇-ZIF) with high H₂ payload, sustained acid-responsive gas release property, and biodegradation. H₂-loaded F₇-ZIF (F₇-ZIF/H₂) effectively released H₂ and Zn²⁺ to induce significant mitochondrial damage and cell apoptosis. More importantly, F₇-ZIF/H₂ considerably upregulated the expression of CD47 (“do not eat me” signal) on tumor cells, which increases target accessibility for anti-CD47 antibody, thereby enhancing their binding efficiency. RNA-seq suggests that the CD47 antibody not only blocks the “do not eat me” signal (mediated by CD47-SIRPα interactions) but also engages Fc receptors on macrophages through its Fc region to trigger antibody-dependent cellular phagocytosis. In melanoma tumor models with small (∼50 mm³) and large sized established tumors (∼200 mm³), the combination of F₇-ZIF/H₂ and anti-CD47 reaches 90% and 83% of tumor inhibition rate, respectively, compared to free anti-CD47. When further combined with anti-PD-L1, the therapeutic system triggers systemic T cell immunity that rejects the progression of both primary and distal tumors. This work provides insights into gas-assisted cancer immunotherapy.Xiang Liu, Weidong Wang, Tianze Wu, Jianing Li, Yimin Gong, Dan Luo, Xianling Guo, Mingli Deng, and Yannan Yan
Engineering Crystallinity Gradients for Tailored CaO(2) Nanostructures: Enabling Alkalinity-Reinforced Anticancer Activity with Minimized Ca(2+)/H(2)O(2) Production
No full textCaO₂ nanoparticles (CNPs) can produce toxic Ca²⁺ and H₂O₂ under acidic pH, which accounts for their intrinsic anticancer activity but at the same time raises safety concerns upon systemic exposure. Simultaneously realizing minimized Ca²⁺/H₂O₂ production and enhanced anticancer activity poses a dilemma. Herein, we introduce a "crystallinity gradient-based selective etching" (CGSE) strategy, which is realized by creating a crystallinity gradient in a CNP formed by self-assembled nanocrystals. The nanocrystals distributed in the outer layer have a higher crystallinity and thus are chemically more robust than those distributed in the inner layer, which can be selectively etched. CGSE not only leads to CNPs with tailored single- and doubleshell hollow structures and metal-doped compositions but more surprisingly enables significantly enhanced anticancer activity as well as tumor growth inhibition under limited Ca²⁺/H₂O₂ production, which is attributed to an alkalinity-reinforced lysosome-dependent cell death pathway.Yiru Shi, Zan Dai, Yue Wang, Jiangqi Luo, Larry Cai, Jie Tang, Chengzhong Yu, and Yannan Yan
Hybrid nanoparticle-mediated simultaneous ROS scavenging and STING activation improve the antitumor immunity of in situ vaccines
No full textIn situ vaccine (ISV) is a versatile and personalized local immunotherapeutic strategy. However, the compromised viability and function of dendritic cells (DCs) in a tumor microenvironment (TME) largely limit the therapeutic efficacy. We designed a hybrid nanoparticle-based ISV, which accomplished superior cancer immunotherapy via simultaneously scavenging reactive oxygen species (ROS) and activating the stimulator of interferon genes (STING) pathway in DCs. This ISV was constructed by encapsulating a chemodrug, SN38, into diselenide bond-bridged organosilica nanoparticles, followed by coating with a Mn2+-based metal phenolic network. We show that this ISV can activate the STING pathway through Mn2+ and SN38 comediated signaling and simultaneously scavenge preexisting H2O2 in the TME and Mn2+-catalyzed •OH by leveraging the antioxidant property of diselenide and polyphenol. This ISV effectively activated DCs and protected them from oxidative damage, leading to remarkable downstream T cell activation and systemic antitumor immunity. This work highlights a nanoparticle design that manipulates DCs in the TME for improving the ISV.Jianing Li, Tianze Wu, Weidong Wang, Yimin Gong, Mingzhu Lu, Mengmeng Zhang, Wanyue Lu, Yaming Zhou, Yannan Yan
Sulfate Radical Based In Situ Vaccine Boosts Systemic Antitumor Immunity via Concurrent Activation of Necroptosis and STING Pathway
No full textPublished online: August 15, 2024In situ vaccine (ISV) can provoke systemic anti-tumor immunity through the induction of immunogenic cell death (ICD). The development of ISV technology has been restricted by the limited and suboptimal ICD driven tumor antigen production which are currently relying on chemo-drugs, photo-/radio-sensitizers, oncolytic-virus and immunostimulatory agents. Herein, a sulfate radical (SO4 ·-) based ISV is reported that accomplishes superior tumor immunotherapy dispense from conventional approaches. The ISV denoted as P-Mn-LDH is constructed by intercalating peroxydisulfate (PDS, a precursor of SO4 ·-) into manganese layered double hydroxide nanoparticles (Mn-LDH). This design allows the stabilization of PDS under ambient condition, but triggers a Mn2+ mediated PDS decomposition in acidic tumor microenvironment (TME) to generate in situ SO4 ·-. Importantly, it is found that the SO4 ·- radicals not only effectively kill cancer cells, but also induce a necroptotic cell death pathway, leading to robust ICD signaling for eliciting adaptive immunity. Further, the P-Mn-LDH can activate the stimulator of interferon genes (STING) pathway to further boost anti-tumor immunity. Collectively, the P-Mn-LDH based ISV exhibited potent activity in inhibiting tumor growth and lung metastasis. When combined with immune checkpoint inhibitor, significant inhibition of distant tumors is achieved. This study underpins the promise of SO4 ·- based vaccine technology for cancer immunotherapy.Yiming Huang, Jie Zou, Jiangyan Huo, Min Zhang,* and Yannan Yan
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