Enhanced Melanoma‐Targeted Therapy by “Fru‐Blocked” Phenyboronic Acid‐Modified Multiphase Antimetastatic Micellar Nanoparticles,Advanced Science

当前位置： X-MOL 学术 › Adv. Sci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Enhanced Melanoma‐Targeted Therapy by “Fru‐Blocked” Phenyboronic Acid‐Modified Multiphase Antimetastatic Micellar Nanoparticles
Advanced Science ( IF 14.3 ) Pub Date : 2018-07-13 , DOI: 10.1002/advs.201800229
Yang Long ₁ , Zhengze Lu ₁ , Ling Mei ₁ , Man Li ₁ , Kebai Ren ₁ , Xuhui Wang ₁ , Jiajing Tang ₁ , Zhirong Zhang ₁ , Qin He ₁

Affiliation

Metastasis remains the main driver of mortality in patients suffering from cancer because of the refractoriness resulting from the multi‐phase metastatic cascade. Herein, a multifunctional self‐delivering PBA‐LMWH‐TOS nanoparticle (PLT NP) is established that acts as both nanocarrier and anti‐metastatic agent with effects on most hematogenous metastases of cancers. The hydrophilic segment (low molecular weight heparin, LMWH) inhibits the interactions between tumor cells and platelets. The hydrophobic segment (d‐α‐tocopheryl succinate, TOS) could inhibit the expression of matrix metalloproteinase‐9 (MMP‐9) in B16F10 cells which is first reported in this article. Surprisingly, even the blank NPs showed excellent anti‐metastatic capacity in three mouse models by acting on different phases of the metastatic cascade. Moreover, the overexpression of sialic acid (SA) residues on tumor cells is implicated in the malignant and metastatic phenotypes of cancers. Thus, these 3‐aminophenylboronic acid (PBA)‐modified doxorubicin (DOX)‐loaded NPs offer an efficient approach for the treatment of both solid melanomas and metastases. Furthermore, a simple pH‐sensitive “Fructose (Fru)‐blocking” coping strategy is established to reduce the NP distribution in normal tissues and distinctly increases the accumulation in melanoma tumors. These micellar NPs consisting of biocompatible materials offer a promising approach for the clinical therapy of highly invasive solid tumors and metastases.

中文翻译：

“Fru-Blocked”苯硼酸修饰多相抗转移胶束纳米颗粒增强黑色素瘤靶向治疗

由于多相转移级联导致的难治性，转移仍然是癌症患者死亡的主要驱动因素。在此，建立了一种多功能自递送 PBA-LMWH-TOS 纳米颗粒（PLT NP），它既可作为纳米载体又可作为抗转移剂，对大多数癌症的血行转移有影响。亲水片段（低分子量肝素，LMWH）抑制肿瘤细胞和血小板之间的相互作用。疏水性片段（d -α-生育酚琥珀酸酯，TOS）可以抑制B16F10细胞中基质金属蛋白酶-9（MMP-9）的表达，这是本文首次报道的。令人惊讶的是，即使是空白纳米颗粒，通过作用于转移级联的不同阶段，在三种小鼠模型中也显示出优异的抗转移能力。此外，肿瘤细胞上唾液酸（SA）残基的过度表达与癌症的恶性和转移表型有关。因此，这些 3-氨基苯硼酸 (PBA) 修饰的负载阿霉素 (DOX) 的纳米颗粒为治疗实体黑色素瘤和转移瘤提供了一种有效的方法。此外，建立了一种简单的 pH 敏感“果糖 (Fru) 阻断”应对策略，以减少正常组织中的 NP 分布，并显着增加黑色素瘤肿瘤中的积累。这些由生物相容性材料组成的胶束纳米粒子为高侵袭性实体瘤和转移瘤的临床治疗提供了一种有前景的方法。

更新日期：2018-07-13

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11