Folic acid-modified Exosome-PH20 enhances the efficiency of therapy via modulation of the tumor microenvironment and directly inhibits tumor cell metastasis.
Folic acid-modified Exosome-PH20 enhances the efficiency of therapy via modulation of the tumor microenvironment and directly inhibits tumor cell metastasis.
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叶酸修饰的 Exosome-PH20 通过调节肿瘤微环境提高治疗效率并直接抑制肿瘤细胞转移。
DOI：
10.1016/j.bioactmat.2020.09.014
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发表时间：
2021-04
影响因子：
18.9
通讯作者：
Yang H
中科院分区：
文献类型：
--
作者：
Feng C;Xiong Z;Wang C;Xiao W;Xiao H;Xie K;Chen K;Liang H;Zhang X;Yang H
透明质酸（HA）在肿瘤微环境中的高积累导致间质压增加和药物灌注减少。此外，高分子量（HMW）-HA抑制M1巨噬细胞极化，增强M2极化，并诱导免疫抑制。透明质酸酶治疗试图减少肿瘤中HA的量。然而，透明质酸酶驱动的HA降解加速了肿瘤细胞转移，这是癌症患者死亡的主要原因。因此，我们设计了一种新的基于外泌体的药物递送系统，命名为Exos-PH 20-FA，利用基因工程表达人透明质酸酶（PH 20）和自组装技术用叶酸（FA）修饰外泌体。我们的结果表明，Exos-PH 20-FA将HMW-HA降解为低分子量（LMW）-HA。此外，LMW-HA使巨噬细胞极化为M1表型，并减少相关免疫抑制免疫细胞的数量，从而将免疫微环境从免疫抑制表型改变为免疫支持表型。此外，我们证明了Exos-PH 20-FA直接减少透明质酸酶诱导的肿瘤细胞转移。这种肿瘤治疗还可以通过FA修饰的肿瘤靶向效应来增强化疗的输送。我们的研究结果表明，Exos-PH 20-FA提高了肿瘤治疗效率，并减少了透明质酸酶治疗的副作用，即肿瘤细胞转移。这种一体化的基于外泌体的HA靶向DDS可能是一种有前途的治疗方法，可以产生更有效和更安全的结果。高分子量透明质酸与肿瘤进展有关。透明质酸的降解促进癌细胞的迁移和转移。叶酸可以靶向肿瘤并抑制肿瘤细胞的迁移。外泌体是化疗药物、叶酸和透明质酸酶的理想载体。
High accumulation of hyaluronan (HA) in the tumor microenvironment leads to an increase in the interstitial pressure and reduction perfusion of drugs. Furthermore, high molecular-weight (HMW)-HA suppresses M1 macrophage polarization, enhances M2 polarization, and induces immunosuppression. Hyaluronidase treatment have attempted to decrease the quantity of HA in tumors. However, hyaluronidase-driven HA degradation driven accelerates tumor cell metastasis, which is a major cause of mortality in cancer patients. Thus, we designed a novel exosome-based drug delivery system (DDS), named Exos-PH20-FA, using genetic engineering to express human hyaluronidase (PH20) and self-assembly techniques to modify the exosomes with folic acid (FA). Our results show that Exos-PH20-FA degraded HMW-HA to low-molecular-weight (LMW)-HA. Moreover, LMW-HA polarized macrophages to the M1 phenotype and reduced the number of relevant immunosuppressive immunocytes which changed the immune microenvironment from an immunosuppressive to immunosupportive phenotype. Furthermore, we demonstrated Exos-PH20-FA directly reduced hyaluronidase-induced metastasis of tumor cells. This tumor treatment also allowed an enhanced delivery of chemotherapy by tumor-targeting effect with FA modification. Our findings indicate that Exos-PH20-FA improves tumor treatment efficiency and reduces the side effects of hyaluronidase treatment, namely tumor cell metastasis. This all-in-one exosome-based HA targeting DDS maybe a promising treatment that yields more efficient and safer results. High molecular-weight hyaluronan is related to tumor progression. The degradation of hyaluronan enhance cancer cell migration and metastasis. Folic acid can target tumor and inhibit tumor cell migration. Exosomes are ideal carriers for chemotherapeutics, folic acid and hyaluronidase.
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影响因子：
33.6
作者：
Jiang D;Liang J;Noble PW
通讯作者：
Noble PW
影响因子：
16
作者：
Hong, Yeonsun;Kim, Yoon Kyoung;Kim, In-San
通讯作者：
Kim, In-San
透明质酸酶增强基于纳米颗粒的光动力肿瘤治疗
影响因子：
10.8
作者：
Gong, Hua;Chao, Yu;Liu, Zhuang
通讯作者：
Liu, Zhuang
影响因子：
19
作者：
Hong, Yeonsun;Nam, Gi-Hoon;Kim, In-San
通讯作者：
Kim, In-San
肿瘤细胞驱动的细胞外基质重塑在转移性过程中触觉驱动。
影响因子：
28.2
作者：
Oudin MJ;Jonas O;Kosciuk T;Broye LC;Guido BC;Wyckoff J;Riquelme D;Lamar JM;Asokan SB;Whittaker C;Ma D;Langer R;Cima MJ;Wisinski KB;Hynes RO;Lauffenburger DA;Keely PJ;Bear JE;Gertler FB
通讯作者：
Gertler FB