Enhanced Melanoma‐Targeted Therapy by "Fru‐Blocked" Phenyboronic Acid‐Modified Multiphase Antimetastatic Micellar Nanoparticles. Issue 11 (13th July 2018)

• Record Type: Journal Article
• Authors: Long, Yang; Lu, Zhengze; Mei, Ling; Li, Man; Ren, Kebai; Wang, Xuhui; Tang, Jiajing; Zhang, Zhirong; He, Qin
• Is Part Of: Advanced science. Volume 5:Issue 11(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-07-13
• Subjects: antimetastatic nanoparticles -- Fru‐blocking -- LMWH -- metastatic cascade -- self‐delivering nanoparticles -- d‐α‐tocopheryl succinate (TOS); Science -- Periodicals; 505
• DOI: 10.1002/advs.201800229
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: 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. Abstract : A multifunctional self‐delivering 3‐aminophenylboronic acid‐low‐molecular‐weight heparin‐d ‐α‐tocopheryl succinate nanoparticle is established as both a nanocarrier and antimetastatic agent that effects hematogenous metastasis of cancers. Both of the hydrophilic segments and the hydrophobic segments could restrain tumor metastasis by acting on different phases of the metastatic cascade. Moreover, a simple "Fru‐blocking" strategy is developed for efficient tumor‐targeting therapy.