Neutrophil Camouflaged Stealth Nanovehicle for Photothermal‐Induced Tumor Immunotherapy by Triggering Pyroptosis

Abstract

The regulation of tumor immunosuppressive microenvironments via precise drug delivery is a promising strategy for preventing tumor recurrence and metastasis. Inspired by the stealth strategy, a stealthy nanovehicle based on neutrophil camouflage is developed to achieve precise delivery and tumor immunotherapy by triggering pyroptosis. The nanovehicle comprises anti-CD11b-and IR820-conjugated bovine serum albumin nanoparticles loaded with decitabine. Camouflaged by neutrophils, the nanovehicles achieve efficient tumor delivery by neutrophil hitchhiking owing to the biotropism of neutrophils for tumors. The fluorescent signal molecule, IR820, on the nanovehicle acts as a navigation monitor to track the precise delivery of the nanovehicle. The released decitabine upregulates gasdermin E, and laser irradiation activates caspase-3, thereby resulting in pyroptosis, which improves the system's adaptive immune response. In a triple-negative breast cancer animal model, it regulates the immunosuppressive microenvironment for effective tumor immunotherapy and induces a long-lasting and strong immune memory to prevent lung metastasis.

A Twindrive Precise Delivery System of Platelet-Neutrophil Hybrid Membrane Regulates Macrophage Combined with CD47 Blocking for Postoperative Immunotherapy

“…This inflammatory chemotactic property entitles neutrophils with excellent ability to target postoperative tumor tissue. Similar to platelets, a neutrophil-based biomimetic drug delivery system also plays an important role in tumor-targeted treatment. ,, Hybrid membrane (PNM) derived from platelet and neutrophil membranes will inherit a variety of abilities of the source cells to obtain twindrive targeting for microenvironment regulation after surgery. Here, the ability of PNM to assist the accumulation of nanoparticles in damaged tumor tissue was demonstrated through in vivo fluorescent imaging guidance of IR820.…”

“…Neutrophils are the most abundant circulating leukocytes, accounting for 40 to 70% of all human white blood cells. In particular, the acute inflammatory microenvironment caused by surgery will activate neutrophils and attract the aggregation of neutrophils during the postoperative treatment of breast cancer. ,− Targeted migration of platelets and neutrophils among these pathological features can also be exploited as a breakthrough for targeted drug delivery. , Although living cells have shown great advantages as drug delivery vehicles, their cumbersome preparation and biosafety remain major challenges that limit their application. , The platelet membrane and neutrophil cell membrane inherit the inherent advantages of primary cells, especially the hybrid membrane can accumulate their targeting characteristics and achieve twindrive targeting and deeper tumor penetration, making it a promising strategy for cancer postoperative delivery carriers. − At the same time, platelet membrane and neutrophil cell membrane can also use their specific adhesion to the surface receptors of circulating tumor cells and tumor-derived exosomes to trap them, cut off their links with immune cells, and inhibit tumor metastasis . Compared to other hybrid membrane delivery systems, the platelet-neutrophil hybrid system played the twindrive delivery role, which can provide targeted delivery through the cumulative action of dual targeting.…”

Anti‐PD‐1/Her2 Bispecific Antibody IBI315 Enhances the Treatment Effect of Her2‐Positive Gastric Cancer through Gasdermin B‐Cleavage Induced Pyroptosis

“…[20,21] There is a growing consensus that pyroptosis induced by tumor cell pyroptosis inducers can improve the body's antitumor immune activity and, when combined with immune checkpoint inhibitors, can transform "cold tumors" into "hot tumors," thereby exerting a synergistic antitumor effect. [17,[22][23][24][25] Accordingly, the occurrence of pyroptosis depends on the production of activated gasdermins. While screening gastric cancer cell lines, PDX-1 and PDXO-1, we focused on GSDMB, and in subsequent knockdown experiments, we confirmed that the pyroptosis and antitumor effects of IBI315mediated T cells were dependent on GSDMB.…”

Advances and applications of nanoparticles in cancer therapy

“…Interestingly, biomimetic designs based on CM coating innovatively combines natural and artificial nanomaterials strengths, endowing NPs with remarkable functions, such as excellent biocompatibility, low immunogenicity, and specific targeting ability 214 . Different CM source, including erythrocytes, platelets (PLTs), macrophages, T‐cells, natural killer (NKs) cells, DCs, tumor cells, and bacteria, endowing various properties to biomimetic NPs 215–221 . As illustrated in Figure 2A, Qing et al 222 fabricated T‐cell‐mimicking NPs which are composed of the T‐CM and dacarbazine‐loaded PLGA NPs to directly kill tumor cells by releasing anticancer drugs and providing FasL.…”