Immunotherapy has become a promising research "hotspot" in cancer treatment. "Soldier" immune cells are not uniform throughout the body; they accumulate mostly in the immune organs such as the spleen and lymph nodes (LNs), etc. The unique structure of LNs provides the microenvironment suitable for the survival, activation, and proliferation of multiple types of immune cells. LNs play an important role in both the initiation of adaptive immunity and the generation of durable anti-tumor responses. Antigens taken up by antigen-presenting cells in peripheral tissues need to migrate with lymphatic fluid to LNs to activate the lymphocytes therein. Meanwhile, the accumulation and retaining of many immune functional compounds in LNs enhance their efficacy significantly. Therefore, LNs have become a key target for tumor immunotherapy. Unfortunately, the nonspecific distribution of the immune drugs in vivo greatly limits the activation and proliferation of immune cells, which leads to unsatisfactory anti-tumor effects. The efficient nano-delivery system to LNs is an effective strategy to maximize the efficacy of immune drugs. Nano-delivery systems have shown beneficial in improving biodistribution and enhancing accumulation in lymphoid tissues, exhibiting powerful and promising prospects for achieving effective delivery to LNs. Herein, the physiological structure and the delivery barriers of LNs were summarized and the factors affecting LNs accumulation were discussed thoroughly. Moreover, developments in nano-delivery systems were reviewed and the transformation prospects of LNs targeting nanocarriers were summarized and discussed. 

/pdf/application-of-nano-delivery-systems-in-lymph-nodes-for-1grbaqeu.pdf

Application of Nano-Delivery Systems in Lymph Nodes for Tumor Immunotherapy

Small extracellular vesicles (sEVs) are known to be secreted by a vast majority of cells. These sEVs, specifically exosomes, induce specific cell-to-cell interactions and can activate signaling pathways in recipient cells through fusion or interaction. These nanovesicles possess several desirable properties, making them ideal for regenerative medicine and nanomedicine applications. These properties include exceptional stability, biocompatibility, wide biodistribution, and minimal immunogenicity. However, the practical utilization of sEVs, particularly in clinical settings and at a large scale, is hindered by the expensive procedures required for their isolation, limited circulation lifetime, and suboptimal targeting capacity. Despite these challenges, sEVs have demonstrated a remarkable ability to accommodate various cargoes and have found extensive applications in the biomedical sciences. To overcome the limitations of sEVs and broaden their potential applications, researchers should strive to deepen their understanding of current isolation, loading, and characterization techniques. Additionally, acquiring fundamental knowledge about sEVs origins and employing state-of-the-art methodologies in nanomedicine and regenerative medicine can expand the sEVs research scope. This review provides a comprehensive overview of state-of-the-art exosome-based strategies in diverse nanomedicine domains, encompassing cancer therapy, immunotherapy, and biomarker applications. Furthermore, we emphasize the immense potential of exosomes in regenerative medicine. 

Extracellular vesicles in nanomedicine and regenerative medicine: A review over the last decade

Immunotherapy is a new type of tumor treatment. In this review, the main focus is on an overview of the research progress of immunotherapy in cancer treatment and the combined application of immunotherapy with other therapeutic approaches. 

Immunotherapy: cancer immunotherapy and its combination with nanomaterials and other therapies

A new frontier in neuropharmacology: Recent progress in natural products research for blood–brain barrier crossing

Bovune milk exosomes (MK-exo) have bioactive effects on the health of consumers and can also serve as excellent drug delivery vehicles. However, long-term preservation and transportation remain major challenges at present. In this report, high-quality MK-exo are prepared on a large scale. We then developed a lyophilization method belonging to MK-exo, and performed acceleration and long-term stability experiments on the lyophilized MK-exo to evaluate the effect of lyophilization. The results showed that the lyophilized MK-exo can be stored at room temperature for at least 3 months and 2-8°C℃ for 15 months. These findings provide data support for further understanding of the properties and applications of MK-exo.

Study on the preparation of bovine milk exosomes and the stability of lyophilized powder

Menthol nanoliposomes enhanced anti-tumor immunotherapy by increasing lymph node homing of dendritic cell vaccines.

Exosomes are small vesicles released from cells and present in various mammal biological fluids, such as bovine milk, which worked for skin care for many years besides dairy. In addition, Exosomes were regarded as a vehicle for intercellular communication. Therefore, we aimed to investigate the novel roles of bovine milk-derived exosomes (MK-Exo) on human skin anti-aging. Purified MK-Exo can be directly uptake by the keratinocytes and fibroblast in vitro and upregulate the expression of the natural factors related to skin moisturizing, including Filaggrin (FLG), Aquaporin 3 (AQP3), CD44 in the keratinocytes and hyaluronidase (HAS2) in the fibroblast, and MK-Exo promoted the cell migration of the fibroblast, while rescue its expression of type I collagen (Col I), type III collagen (Col III) after ultraviolet radiation. Furthermore, the phototoxicity test, photoallergy test, repeated skin irritation test, skin allergy test, and patch test confirm the safety of MK-Exo on the skin. Finally, the roles of MK-Exo in preserving moisture and anti-wrinkle were also identified in humans. Then, MK-Exo was smeared on the facial skin of 31 female volunteers twice a day for 28 days, and the functions were evaluated following the safety assessment in vivo. These studies reveal the novel roles of bovine milk-derived exosomes in human skin aging, which opens a new way of skin care.

/pdf/the-novel-roles-of-bovine-milk-derived-exosomes-on-skin-anti-jyhdq4mg.pdf

The novel roles of bovine milk-derived exosomes on skin anti-aging

Background: Biochanin A is an excellent dietary isoflavone that has the concomitant function of both medicine and foodstuff.The attenuation function of biochanin A on blood-brain barrier (BBB) damage induced by cerebral ischemia-reperfusion remains unclear.Methods: C57BL/6 mice were subjected to 1 h middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion.The infarct volume of the brain was stained by TTC, while leakage of the brain was quantitatively stained by Evans blue, and the neurologic deficit score was measured.Microglial-induced morphologic changes were observed via immunofluorescence staining, and rolling and adhering leukocytes in venules were observed via two-photon imaging, while the inner fluorescein isothiocyanate-albumin of venules were compared with those of surrounding interstitial area through venular albumin leakage.Results: The attenuation effect of biochanin A on tight junction injury was compared in ischemia-reperfusion mice or conventional knockdown of leucine-rich α2-glycoprotein 1 (Lrg1) mice.Biochanin A could ameliorate BBB injury in mice with cerebral ischemiareperfusion in a dose-dependent manner by strengthening the immunostaining volume of occludin, claudin-5, and zonula occludens-1.The amoeba morphologic changes of microglial combined with the elevated expression of Lrg1 could be relieved under the treatment of biochanin A. Biochanin A played a countervailing role on the rolling leukocytes in the vessel, while the leakage of blood vessels was reduced.Biochanin A diminished its functions to further improved attenuation for tight junction injury on conventional Lrg1-knockout mice, as well as the inhibition effects on TGF-β1, and the phosphorylation of suppressor of mothers against decapentaplegic 2 (Smad2)/Smad2 via western blot assay.Conclusion: Biochanin A could alleviate tight junction injury induced by cerebral ischemiareperfusion and blocked the Lrg1/TGF-β/Smad2 pathway to modulate leukocyte migration patterns. 

Biochanin A, as the Lrg1/TGF-β/Smad2 pathway blockade, attenuates blood-brain barrier damage after cerebral ischemia-reperfusion by modulating leukocyte migration patterns

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Menthol nanoliposomes enhanced anti-tumor immunotherapy by increasing lymph node homing of dendritic cell vaccines.

The novel roles of bovine milk-derived exosomes on skin anti-aging

Biochanin A, as the Lrg1/TGF-β/Smad2 pathway blockade, attenuates blood-brain barrier damage after cerebral ischemia-reperfusion by modulating leukocyte migration patterns