![]() provided hematoxylin and eosin (HE), Ki-67 immunofluorescence detection kit, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) immunofluorescence detection kit. ![]() Servicebio Biological Technology Co., Ltd. β-Actin (60008-1-Ig) mouse primary antibody was provided by Proteintech Group, Inc. CCL5 rabbit primary antibody was provided by Solarbio Biotechnology Co., Ltd. ICAM-2 (F-5) mouse primary antibody was purchased from Santa Cruz Biotechnology Co., Ltd. P-selectin rabbit primary antibody was provided by Shanghai Lianshuo Biological Technology Co., Ltd. Polyvinylidene fluoride (PVDF) membrane was produced by Cell Signaling Technology, Co., Ltd. BCA Protein Quantitation Kit and Coomassie Blue Fast Staining Solution were from Beyotime Biology Co., Ltd. Bovine serum albumin (BSA) was procured from Yeasen Biological Technology Co., Ltd. provided RPMI-1640, phosphate buffer saline (PBS), trypsin, Cy5, and non-pre-stained protein marker. In this study, we applied the tumor-transplanted mouse model and intravenously injected activated platelet membrane nanovesicles to investigate the mechanism of enhancing antitumor immunity by recruiting neutrophils, thus exploring a new perspective for tumor treatment. Whether activated platelet membrane nanovesicles alone can target tumor sites and whether targeting tumor sites is beneficial for recruiting neutrophils to the tumor site has not been reported. It has been reported that activated platelet membrane nanovesicles camouflaging black phosphorus quantum dots can target tumor tissue ( Shang et al., 2019). In addition, they also express intercellular adhesion molecule-2 (ICAM-2) and CCL5, and recruit neutrophils mediated by P-selectin glycoprotein ligand 1 (PSGL-1), CCL receptor 1/CCL receptor 5 (CCR1/CCR5), and lymphocyte function-associated antigen 1 (LFA1) ( Weber and Springer, 1997 Kuijper et al., 1998 von Hundelshausen et al., 2007).Īlthough biodegradable and clearable inorganic nanomaterials show progress in cancer theranostics ( Wang et al., 2021), bionics and targeted nanotechnology still play an irreplaceable role. Platelets perform a vital part in recruiting neutrophils through self-expressed P-selectin ( Nagao et al., 2007). In addition, neutrophils recruit and activate T cells by secreting cytokines, such as TNF-α, cathepsin G, and neutrophils elastase ( Mishalian et al., 2014). ![]() There is evidence that neutrophils can cross-present neoantigens to T lymphocytes via major histocompatibility complex (MHC), leading to the initiation of antitumor T-cell response ( Singhal et al., 2016), and stimulating T-cell proliferation and activation ( Eruslanov et al., 2014). One study showed that CD8 +, CD4 + T cells, and B cells are positively correlated with the reduction of tumor volume ( Cunha et al., 2012). Neutrophils control the vital part of the adaptive immune system, regulating the function of B and T cells ( Liew and Kubes, 2019), stimulating T-cell-mediated antitumor response ( Eruslanov et al., 2014). Neutrophils exhibit significant antitumor effect and can prime anticancer immunity ( Ustyanovska Avtenyuk et al., 2020). After treatment with aPNs, not only the number of neutrophils, CD8 +, CD4 + T cells, and B cells increased, but also IL-12, TNF-α, and IFN-γ levels elevated significantly in tumor tissues. In vivo results of a mouse model of breast cancer-transplanted tumor showed that tumor volume reduced significantly, Ki-67-positive tumor cells decreased, and TUNEL-positive tumor cells increased in tumors after treatment with activated platelet membrane nanovesicles (aPNs). Western blotting showed that both the activated platelets and the platelet membrane nanovesicles expressed P-selectin, ICAM-2, and CCL5. The results of SDS-PAGE showed that the platelet membrane nanovesicles retained almost all the proteins of platelets. Whether activated platelet membrane nanovesicles can recruit neutrophils has not been reported, nor has their role in antitumor immunity. In this study, we prepared platelet membrane nanovesicles from activated platelets. Platelets play a crucial role in the recruitment of neutrophils, mediated by P-selectin, CCL5, and ICAM-2.
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