MT1-MMP Responsive Doxorubicin Conjugated Poly(lactic-co-glycolic Acid)/Poly(styrene-alt-maleic Anhydride) Core/Shell Microparticles for Intrahepatic Arterial Chemotherapy of Hepatic Cancer

作者：Davaa Enkhzaya; Lee Junghan; Jenjob Ratchapol; Yang Su Geun^*

来源：ACS Applied Materials & Interfaces, 2017, 9(1): 71-79.

DOI：10.1021/acsami.6b08994

• microparticle
• poly(D,L-lactide-co-glycolide)
• poly(styrene-alt-maleic anhydride)
• doxorubicin
• hepatoma

In this study, we demonstrated, that the MT1-MMP-responsive peptide (sequence: GPLPLRSWGLK) and doxorubicin-conjugated poly(lactic-co-glycolic acid/poly-(styrene-alt-maleic anhydride) core/shell microparticles (PLGA/pSMA. MPs) can be applied for intrahepatic arterial injection for hepatocellular carcinoma (HCC). PLGA/pSMA MPs were prepared with a, capillary-focused microfluidic device: The particle size, observed by scanning electron microscopy (SEM), was, around 22 +/- 3 mu m. MT1-MMP-responsive peptide and doxorubicin (D-OX) were chemically conjugated with pSMA segments on the shell of MPs to form. a PLGA/pSMA-peptide-DOX complex, resulting in high encapsulation efficiency, (91.1%) and loading content (2.9%). DOX was released from PLGA/pSMA-peptide-DOX MPs in a pH-dependent manner (similar to 25% at pH 5.4 and similar to 8% at pH 7.4) and accumulated significantly in an MT1-MMP-overexpressing Hep3B cell line. An in vivo intrahepatic injection study showed localization of MPs on the hepatic vessels and hepatic lobes up to 24 h after the injection without any shunting to the lung. Moreover, MPs efficiently inhibited tumor growth of Hep3B hepatic tumor xenografted mouse models. We expect that PLGA/pSMA-peptide-DOX MPs can be Utilized as an effective intrahepatic drug delivery system for the treatment of HCC.

• 出版日期2017-1-11