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 作者： Weiqin Wanga. Mengying Lia. Zhenhai Zhangb. Changchang Cuia. Jianping Zhoua. Lifang Yina. Huixia Lva.

a

Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 210009, China

b

Key Laboratory of New Drug Delivery System of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, 210028, China

 

摘要：A novel tLyP-1-HA-PTX conjugate is designed for combining the solubilization capacity of Paclitaxel (PTX) and tumor tissue targeting – penetration effect of hyaluronic acid (HA) as well as cell penetration peptide (tLyP-1). In addition, through modifying by tLyP-1, the anticancer scope of tLyP-1-HA-PTX conjugate was expanded from tumor cells expressing CD44 receptors to those of expressing NRP1 receptors. In vitro antitumor ability of tLyP-1-HA-PTX conjugate and cellular uptake tests were conducted to testify the tumor-targeting behavior of the conjugates. The results showed that both HA-PTX and tLyP-1-HA-PTX conjugates gained better solubility, better stability and specific tumor sites ability and showed high safety in vitro cytotoxicity tests. The tLyP-1-HA-PTX conjugate was especially endowed with efficient cell-penetrating and tumor NRP1 receptor targeting ability and compensate for the decreasing of uptake caused by suppression of CD44 receptor, which is more significant when NRP1 receptor is highly expressed.