Multifunctional self-delivery micelles targeting the invasion-metastasis cascade for enhanced chemotherapy against melanoma and the lung metastasis.
Multifunctional self-delivery micelles targeting the invasion-metastasis cascade for enhanced chemotherapy against melanoma and the lung metastasis.
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DOI：
10.1016/j.ajps.2021.08.002
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发表时间：
2021-11
影响因子：
10.2
通讯作者：
He Q
中科院分区：
文献类型：
--
作者：
Xu S;Liu C;Zang S;Li J;Wang Y;Ren K;Li M;Zhang Z;He Q
肿瘤转移与肿瘤患者的高死亡率密切相关，并受到多种信号通路的调控。因此，这种生物过程的多相阻断对于癌症治疗是有益的。在此，我们通过合成D-α-生育酚琥珀酸酯（TOS）缀合的硫酸软骨素（CS）（CT NPs）来建立多功能自递送系统，其既作为纳米载体又作为影响转移级联的不同阶段的抗转移剂。CT纳米粒的疏水段TOS可抑制基质金属蛋白酶-9的分泌，亲水段CS通过CD 44受体靶向B16 F10细胞，减少肿瘤细胞与血小板的相互作用。结果表明，CT NPs能够通过干扰转移级联的多相性在体外和体内成功地抑制转移。在包封化疗药物阿霉素（DOX）后，所获得的胶束CT/DOX有效地抑制荷B16 F10小鼠中的原发性肿瘤生长和转移。因此，合理设计的由生物相容性材料组成的多功能纳米颗粒对实体瘤和转移瘤具有优异的治疗效果。(A)CT/DOX纳米粒的制备示意图。亲水性CS和疏水性TOS通过酯键连接，然后自组装成良好定义的胶束，通过超声乳化制备负载DOX的纳米粒。(B)CT/DOX纳米粒在靶向黑色素瘤实体瘤和抑制肺转移中的作用
Metastasis is closely related to the high mortality of cancer patients, which is regulated by multiple signaling pathways. Hence, multiphase blocking of this biological process is beneficial for cancer treatments. Herein, we establish a multifunctional self-delivering system by synthesizing D-α-tocopheryl succinates (TOS)-conjugated chondroitin sulfate (CS) (CT NPs), which both serve as nanocarrier and antimetastatic agent that affects different phases of the metastatic cascade. TOS as the hydrophobic segment of CT NPs can inhibit the secretion of matrix metalloproteinase-9, while the hydrophilic segment CS targets B16F10 cells through CD44 receptors and reduces the interaction between tumor cells and platelets. The results show that CT NPs are able to inhibit metastasis successfully both in vitro and in vivo by interfering the multiphase of the metastatic cascade. Following encapsulating chemotherapeutic drug doxorubicin (DOX), the obtained micelles CT/DOX efficiently suppress both primary-tumor growth and metastases in B16F10 bearing mice. As a result, the rationally designed multifunctional NPs composing of biocompatible materials provide excellent therapeutic effects on solid tumors and metastases. (A) Schematic illustration of the preparation of CT/DOX NPs, The hydrophilic CS and the hydrophobic TOS were linked by ester bonds and then self-assembled into well-defined micelles, DOX-loaded NPs were prepared by ultrasonic emulsification. (B) The roles of CT/DOX NPs in targeting a melanoma solid tumor and inhibiting lung metastasis.
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影响因子：
17.1
作者：
Beldman TJ;Senders ML;Alaarg A;Pérez-Medina C;Tang J;Zhao Y;Fay F;Deichmöller J;Born B;Desclos E;van der Wel NN;Hoebe RA;Kohen F;Kartvelishvily E;Neeman M;Reiner T;Calcagno C;Fayad ZA;de Winther MPJ;Lutgens E;Mulder WJM;Kluza E
通讯作者：
Kluza E
影响因子：
50.3
作者：
Hiratsuka, S;Nakamura, K;Shibuya, M
通讯作者：
Shibuya, M
分子机制和血管生成的临床应用。
影响因子：
64.8
作者：
Carmeliet, Peter;Jain, Rakesh K.
通讯作者：
Jain, Rakesh K.
影响因子：
50.3
作者：
Labelle M;Begum S;Hynes RO
通讯作者：
Hynes RO
DOI：
10.1038/nrc3004
发表时间：
2011-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Gay LJ;Felding-Habermann B
通讯作者：
Felding-Habermann B