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Approximately 15-40% of all cancers develop metastases in the central nervous system (CNS), yet few therapeutic options exist to treat them. Cancer therapies based on monoclonal antibodies are widely successful, yet have limited efficacy against CNS metastases, owing to the low levels of the drug reaching the tumour site. Here, we show that the encapsulation of rituximab within a crosslinked zwitterionic polymer layer leads to the sustained release of rituximab as the crosslinkers are gradually hydrolysed, enhancing the CNS levels of the antibody by approximately tenfold with respect to the administration of naked rituximab. When the nanocapsules were functionalized with CXCL13-the ligand for the chemokine receptor CXCR5, which is frequently found on B-cell lymphoma-a single dose led to improved control of CXCR5-expressing metastases in a murine xenograft model of non-Hodgkin lymphoma, and eliminated lymphoma in a xenografted humanized bone marrow-liver-thymus mouse model. Encapsulation and molecular targeting of therapeutic antibodies could become an option for the treatment of cancers with CNS metastases.

Metabolic reprogramming is a key characteristics of tumor cells, mainly manifested by abnormal metabolism and tumor hypoxia. Here, the design of PolyFBODIPY characterized by the presence of BODIPY photosensitizers, fluorinated aliphatic chains as Oxygen affinity materials, and reactive oxygen species‐sensitive thioketal linkers is reported. PolyFBODIPY subsequently self‐assembles into NP@PolyFBODIPY which is capable of delivering oxygen and photosensitizers simultaneously and generating ROS under light irradiation, resulting in rapid polymer degradation and nanoparticle dissociation via breaking ROS‐sensitive thiol ketal linkers. NP@PolyFBODIPY can target hypoxic tumor plasticity to reprogram metabolism for recapturing photodynamic‐immunotherapy sensitivity for completely inhibiting tumor growth on multi‐drug‐resistant patient‐derived lung cancer xenografts (PDXMDR). Moreover, NP@PolyFBODIPY‐mediated photodynamic‐immunotherapy activates antitumor immune responses and effectively inhibits tumor growth and lung metastasis on an orthotropic metastatic triple‐negative breast cancer model. Mechanistically, metabolomics and lipidomics analysis reveals that NP@PolyFBODIPY‐mediated photodynamic‐immunotherapy not only destroys the redox state of cancer cells, but also affects the metabolism of lipid, amino acid, and d‐glutamine, thereby finally promoting autophagy and apoptosis and inhibiting the proliferation of cancer cells. These results highlight the potential of clinical translation of NP@PolyFBODIPY in targeting hypoxic tumor plasticity via oxygen supply, which reprograms the cellular metabolism for recapturing photodynamic‐immunotherapy sensitivity. [ABSTRACT FROM AUTHOR]

Poor immunogenicity seriously hampers the broader implementation of antitumor immunotherapy. Enhanced immunogenicity capable of achieving greater antitumor immunity is urgently required. Here, a novel polymer that contains hydrophobic ferrocene (Fc) units and thioketal bonds in the main chain, which further delivered a prodrug of oxaliplatin and artesunate, i.e., Artoxplatin, to cancer cells is described. This polymer with Fc units in the nanoparticle can work as a polyigniter to spark the peroxide bonds in Artoxplatin and generate abundant reactive oxygen species (ROS) to kill cancers as nanobombig for cancer therapy. Moreover, ROS can trigger the breakdown of thioketal bonds in the polymer, resulting in the biodegradation of the polymer. Importantly, nanobombig can facilitate the maturation of dendritic cells and promote the activation of antitumor immunity, through the enhanced immunogenic cell death effect by ROS generated in situ. Furthermore, metabolomics analysis reveals a decrease in glutamine in nanobombig‐treated cancer cells, resulting in the upregulation of programmed death ligand 1 (PD‐L1). Consequently, it is further demonstrated enhanced tumor inhibitory effects when using nanobombig combined with anti‐PD‐L1 therapy. Overall, the nanosystem offers a rational design of an efficient chemo‐immunotherapy regimen to promote antitumor immunity by improving tumor immunogenicity, addressing the key challenges cancer immunotherapy faced. [ABSTRACT FROM AUTHOR]

Possessing the largest surface area of mucosa in the body, the gastrointestinal (GI) tract can easily sufferfrom inflammatory damage under various adverse external exposures, resulting in the occurrence of inflammatory bowel disease (IBD). Excessive reactive oxygen species (ROS) usually lead to local mucosal injury, accelerate the formation of niduses, andamplify the inflammatory and immune response. Antioxidant therapy, therefore, is considered as a potential strategy against IBDs. Herein, a series of novel dihydromyricetin‐based nanoassemblies with excellent antioxidant activities and high dispersion in GI tract as oral preparations are developed for the targeted IBD treatment. By changing raw materials, the current strategy can be well extended to the preparation of other insoluble natural flavonoid compound‐based nanoassemblies. The well‐designed dihydromyricetin‐PEG 1000‐based nanoassemblies (DMY‐1000 NAs) with high stability and great ROS scavenging capacity in the harsh environment of GI tract hold an admirable targeted capability toward the intestinal inflamed lesions. Therefore, these biocompatible DMY‐1000 NAs show promising therapeutic effects for typical IBDs including ulcerative colitis and Crohn's disease in murine models. This study not only provides a new method for constructing antioxidant therapy platforms but also illustrates their prominent therapeutic promise against IBDs. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) has emerged as a promising cancer treatment modality; however, its therapeutic efficacy is greatly limited by tumor hypoxia. In this study, a metal‐organic framework (MOF)‐based hydrogel (MOF Gel) system that synergistically combines PDT with the supply of oxygen is designed. Porphyrin‐based Zr‐MOF nanoparticles are synthesized as the photosensitizer. MnO2 is decorated onto the surface of the MOF, which can effectively convert H₂O₂ into oxygen. Simultaneously, the incorporation of MnO2‐decorated MOF (MnP NPs) into a chitosan hydrogel (MnP Gel) serves to enhance its stability and retention at the tumor site. The results show that this integrated approach significantly improves tumor inhibition efficiency by relieving tumor hypoxia and enhancing PDT. Overall, the findings underscore the potential for employing nano‐MOF‐based hydrogel systems as promising agents for cancer therapy, thus advancing the application of multifunctional MOFs in cancer treatment. [ABSTRACT FROM AUTHOR]

Camptothecin (CPT) is a potent chemotherapeutic agent for various cancers, but the broader application of CPT is still hindered by its poor bioavailability and systemic toxicity. Here, a prodrug that releases CPT in response to glutathione (GSH), which is commonly overexpressed by cancer cells is reported. Through assembling with PEGylated lipids, the prodrug is incorporated within as‐assembled nanoparticles, affording CPT with a prolonged half‐life in blood circulation, enhanced tumor targetingability, and improved therapeutic efficacy. Furthermore, such prodrug nanoparticles can also promote dendritic cell maturation and tumor infiltration of CD8+ T cells, providing a novel strategy to improve the therapeutic efficacy of CPT. [ABSTRACT FROM AUTHOR]