Galactose-Containing Polymer-DOX Conjugates for Targeting Drug Delivery.
A novel multifunctional drug delivery system was fabricated by conjugating galactose-based polymer, methoxy-poly(ethylene glycol)-block-poly(6-O-methacryloyl-D-galactopyranose) (mPEG-b-PMAGP) with doxorubicin (DOX) via an acid-labile carbamate linkage. The mPEG-b-PMAGP-co-DOX nanoparticles were spherical in shape, and the diameter determined by dynamic light scattering (DLS) was 54.84 ± 0.58 nm, larger than that characterized by transmission electron microscopy (TEM). The in vitro drug release profiles were studied, and the release of DOX from the nanoparticles was pH-responsive. The cellular uptake behavior of free-DOX and mPEG-b-PMAGP-co-DOX nanoparticles by asialoglycoprotein (ASGP) receptor-positive cancer cell line (HepG2) and ASGP receptor-negative cancer cell lines (MCF-7 and A549 cells) was evaluated by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM), respectively. The mPEG-b-PMAGP-co-DOX nanoparticles which contain galactose functional groups exhibited higher cellular uptake behavior via ASGP receptor-mediated endocytosis in HepG2 cells than in other two cancer cells. The in vitro cytotoxicity assay manifested that the mPEG-b-PMAGP-co-DOX nanoparticles exhibited higher anticancer efficacy against HepG2 cells than MCF-7 cells. These results indicated that the multifunctional mPEG-b-PMAGP-co-DOX nanoparticles possessing pH-responsible and hepatoma-targeting function have great potential to be used as a targeting drug delivery system for hepatoma therapy.
School of Pharmacy, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, People's Republic of China.
Yujie
Y
Sun
School of Pharmacy, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, People's Republic of China.
Jing
J
Zhang
Merial New Zealand, 14 Blackburn Road, Auckland, New Zealand.
Jian
J
Han
School of Pharmacy, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, People's Republic of China.
Baocheng
B
Tian
School of Pharmacy, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, People's Republic of China.
Yanan
Y
Shi
School of Pharmacy, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, People's Republic of China.
Yuanyuan
Y
Ding
School of Pharmacy, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, People's Republic of China.
Lele
L
Wang
School of Pharmacy, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, People's Republic of China. hanjingtian002@163.com.
Jingtian
J
Han
D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000737:chemistry; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation / Q000187:drug effects; D005690:Galactose / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*
D000970:Antineoplastic Agents; D011108:Polymers; D011092:Polyethylene Glycols; D004317:Doxorubicin; C028210:monomethoxypolyethylene glycol; D005690:Galactose
galactose; nanoparticles; pH-responsive; polymer-DOX conjugate; targeting drug delivery