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  • S Kossatz J Grandke P Couleaud A Latorre

    2020-08-12

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    Contents lists available at ScienceDirect
    Colloids and Surfaces B: Biointerfaces
    journal homepage: www.elsevier.com/locate/colsurfb
    Anticancer activity of polymeric nanoparticles containing linoleic acid-SN38 T (LA-SN38) conjugate in a murine model of colorectal cancer
    Guilin Chenga,1, Xiaomin Zhang b,1, Yidan Chenc, Robert J. Leed, Jiangfeng Wanga, Ju Yaob, Yingxin Zhangb, Cheng Zhange, Kaifeng Wangf, , Bo Yub, a Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, PR China b Hangzhou PushKang Biotechnology Co., Ltd., Hangzhou 310030, Zhejiang, PR China c Hangzhou Cancer Institution, Hangzhou Cancer Hospital, Hangzhou 310002, Zhejiang, PR China d Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA e Class 8 of Shaoxing No. 1 High School, Shaoxing 312000, Zhejiang, PR China f Department of Abdominal Oncology, Hangzhou Cancer Hospital, Hangzhou 310002, Zhejiang, PR China
    Keywords:
    Polymeric nanoparticles
    Linoleic acid conjugated SN38
    Drug delivery
    Colorectal cancer 
    Biodegradable polymeric nanoparticles (NPs) have been used frequently as nanocarriers for anticancer drugs. Linoleic acid conjugated SN38 (LA-SN38)-loaded NPs (EBNPs) were developed using biodegradable poly (ethylene oxide)-poly (butylene oxide) (PEO-PBO) diblock copolymer by titration hydration method without using a toxic organic solvent. The EBNPs had high drug loading efficiency and entrapment efficiency for LA-SN38, at 7.53% and 93.55%, respectively. The polydispersity index (PDI) and average diameter were 0.173 ± 0.019 and 226.1 ± 1.2 nm, respectively. The transmission electron microscope (TEM) image pre-sented that the NPs were homogeneous in size and had spherical structures. In vitro study showed the release behavior of EBNPs was slow and sustained. Furthermore, cytotoxicity and apoptosis assay proved that EBNPs were more effective in growth inhibition of human colon cancer cells. Cell uptake experiments further de-monstrated that EBNPs could avoid the phagocytosis by macrophages and promote the uptake by cancer cells. In vivo, EBNPs had prolonged blood circulation time and tumor selectivity in biodistribution. The tumor inhibitory rate of EBNPs was higher compared to SNPs group and CPT-11group (P < 0.01), and the drug did not show significant systemic toxicity at the tested dose. These results indicated that EBNPs are a promising candidate for delivery of LA-SN38 to treat colorectal cancer.
    1. Introduction