Bufalin-loaded mPEG-PLGA-PLL-cRGD nanoparticles: preparation, cellular uptake, tissue distribution, and anticancer activity.
BACKGROUND
Recent studies have shown that bufalin has a good antitumor effect but has high toxicity, poor water solubility, a short half-life, a narrow therapeutic window, and a toxic dose that is close to the therapeutic dose, which all limit its clinical application. This study aimed to determine the targeting efficacy of nanoparticles (NPs) made of methoxy polyethylene glycol (mPEG), polylactic-co-glycolic acid (PLGA), poly-L-lysine (PLL), and cyclic arginine-glycine-aspartic acid (cRGD) loaded with bufalin, ie, bufalin-loaded mPEG-PLGA-PLL-cRGD nanoparticles (BNPs), in SW620 colon cancer-bearing mice.


METHODS
BNPs showed uniform size. The size, shape, zeta potential, drug loading, encapsulation efficiency, and release of these nanoparticles were studied in vitro. The tumor targeting, cellular uptake, and growth-inhibitory effect of BNPs in vivo were tested.


RESULTS
BNPs were of uniform size with an average particle size of 164 ± 84 nm and zeta potential of 2.77 mV. The encapsulation efficiency was 81.7% ± 0.89%, and the drug load was 3.92% ± 0.16%. The results of in vitro cytotoxicity studies showed that although the blank NPs were nontoxic, they enhanced the cytotoxicity of bufalin in BNPs. Drug release experiments showed that the release of the drug was prolonged and sustained. The results of confocal laser scanning microscopy indicated that BNPs could effectively bind to human umbilical vein endothelial cells. In the SW620 xenograft mice model, the BNPs could effectively target the tumor in vivo. The BNPs were significantly more effective than other NPs in preventing tumor growth.


CONCLUSIONS
BNPs had even size distribution, were stable, and had a slow-releasing and tumor-targeting effect. BNPs significantly inhibited colon cancer growth in vitro and in vivo. As a novel drug carrier system, BNPs are a potentially promising targeting treatment for colon cancer.
Department of Clinical Oncology, Putuo Hospital and Interventional Cancer Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Peihao
P
Yin
Yan
Y
Wang
YanYan
Y
Qiu
LiLi
L
Hou
Xuan
X
Liu
Jianmin
J
Qin
Yourong
Y
Duan
Peifeng
P
Liu
Ming
M
Qiu
Qi
Q
Li
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002018:Bufanolides / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D010316:Particle Size; D011091:Polyesters / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D011107:Polylysine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D013056:Spectrophotometry, Ultraviolet; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D002018:Bufanolides; D004337:Drug Carriers; D009842:Oligopeptides; D011091:Polyesters; C574222:monomethoxy (polyethylene glycol)-poly(lactide-co-glycolide)-poly(lysine); D011107:Polylysine; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid; C022777:bufalin