title: Design, synthesis and evaluation of multi-functional tLyP-1-hyaluronic acid-paclitaxel conjugate endowed with broad anticancer scope.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 210009, China. Electronic address: wangwq1203@163.com.
authors.forename: Weiqin
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 210009, China.
authors.forename: Mengying
authors.initials: M
authors.lastname: Li
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, 210028, China.
authors.forename: Zhenhai
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 210009, China.
authors.forename: Changchang
authors.initials: C
authors.lastname: Cui
authors.affiliation: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 210009, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 210009, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Yin
authors.affiliation: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 210009, China. Electronic address: lvhuixia@163.com.
authors.forename: Huixia
authors.initials: H
authors.lastname: Lv
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D006461:Hemolysis; D006801:Humans; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid / Q000494:pharmacology*; D017239:Paclitaxel / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D017239:Paclitaxel
keywords: CD44 receptor; Hyaluronic acid; NRP1 receptor; Paclitaxel; Tumor targeting; tLyP-1