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酵母细胞壁衍生的杂化水凝胶用于光热和免疫联合治疗以增强抗黑色素瘤疗效。

A Yeast Cell Wall Derived Hybrid Hydrogel with Photothermal and Immune Combined Modality Therapy for Enhanced Anti-Melanoma Efficacy.

机构信息

School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, People's Republic of China.

The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.

出版信息

Int J Nanomedicine. 2023 Sep 21;18:5423-5440. doi: 10.2147/IJN.S409674. eCollection 2023.

DOI:10.2147/IJN.S409674
PMID:37767196
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10520258/
Abstract

INTRODUCTION

The effect of traditional treatment for melanoma is quite limited, especially for its recurrence. As the major components of yeast cell wall, chitin and β-glucan exhibit good immune activation effect and are promising candidates for adjuvant. Therefore, melanoma cell membrane (CM) and indocyanine green (ICG) was loaded in a chitin and β-glucan hybrid hydrogel to achieve an enhanced anti-melanoma therapy.

METHODS

The novel hybrid hydrogel was prepared, and its physicochemical properties were examined. Its effect towards melanoma prevention and treatment was evaluated via a melanoma-bearing mice model.

RESULTS

The CM-ICG-hybrid hydrogel was successfully prepared with excellent injectability, self-healing, drug loading, rheological, in vitro and in vivo photothermal stability, and retention properties. It also exhibited good cellular and in vivo safety profiles. In the primary melanoma mice model, it quickly ablated the in-situ melanoma, effectively inhibited the tumor growth, increased the survival rate of melanoma-bearing mice, and increased the level of IFN-γ and TNF-α. In the distal secondary melanoma model, it efficiently prevented the reoccurrence of melanoma and activated the memory T cells. In both models, a synergistic effect of photothermal therapy and immune therapy was found. The hydrogel effectively recruited CD3 CD4 T cells and CD3 CD8 T cells, inhibited the proliferation of melanoma cells, and induced the apoptosis of melanoma cells.

CONCLUSION

The hybrid hydrogel was successfully prepared, and it showed excellent efficacy towards melanoma prevention and treatment due to its efficient tumor ablation and immune activation capability.

摘要

简介

传统的黑色素瘤治疗效果相当有限,尤其是对于其复发。作为酵母细胞壁的主要成分,几丁质和β-葡聚糖具有良好的免疫激活作用,是有前途的佐剂候选物。因此,黑色素细胞膜(CM)和吲哚菁绿(ICG)被负载在几丁质和β-葡聚糖杂化水凝胶中,以实现增强的抗黑色素瘤治疗。

方法

制备了新型杂化水凝胶,并对其理化性质进行了研究。通过黑色素瘤荷瘤小鼠模型评价其对黑色素瘤预防和治疗的作用。

结果

成功制备了 CM-ICG-杂化水凝胶,具有良好的可注射性、自修复性、载药能力、流变学性能、体外和体内光热稳定性以及保留性能。它还表现出良好的细胞和体内安全性。在原发性黑色素瘤小鼠模型中,它迅速消融原位黑色素瘤,有效抑制肿瘤生长,提高黑色素瘤荷瘤小鼠的存活率,并增加 IFN-γ和 TNF-α的水平。在远端继发性黑色素瘤模型中,它有效地防止黑色素瘤的复发并激活记忆 T 细胞。在这两种模型中,都发现了光热治疗和免疫治疗的协同作用。该水凝胶有效地招募了 CD3 CD4 T 细胞和 CD3 CD8 T 细胞,抑制黑色素瘤细胞的增殖,并诱导黑色素瘤细胞的凋亡。

结论

成功制备了杂化水凝胶,由于其高效的肿瘤消融和免疫激活能力,显示出优异的黑色素瘤预防和治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3c/10520258/9db32e490690/IJN-18-5423-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3c/10520258/9b260175b872/IJN-18-5423-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3c/10520258/e4ceaac4de98/IJN-18-5423-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3c/10520258/01e2ef142629/IJN-18-5423-g0003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3c/10520258/8cb926b71741/IJN-18-5423-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3c/10520258/1979554ee203/IJN-18-5423-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3c/10520258/5623d961e020/IJN-18-5423-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3c/10520258/9db32e490690/IJN-18-5423-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3c/10520258/9b260175b872/IJN-18-5423-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3c/10520258/e4ceaac4de98/IJN-18-5423-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3c/10520258/01e2ef142629/IJN-18-5423-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3c/10520258/f68f77213652/IJN-18-5423-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3c/10520258/8cb926b71741/IJN-18-5423-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3c/10520258/1979554ee203/IJN-18-5423-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3c/10520258/5623d961e020/IJN-18-5423-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3c/10520258/9db32e490690/IJN-18-5423-g0008.jpg

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本文引用的文献

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A hybrid hydrogel composed of chitin and β-glucan for the effective management of wound healing and scarring.
一种由壳聚糖和β-葡聚糖组成的杂化水凝胶,可有效管理伤口愈合和瘢痕形成。
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