摘要：β-Lapachone (β-Lap) is a promising orthonaphthoquinone drug for cancer treatment and has been inclinical trials. Its application is constrained by the low aqueoussolubility, and severe side effects. Even prodrug designation isan effective approach to render it with tumor selectivity, it islimited by the lack of modifiable groups on β-Lap. Herein, anovel azo bond primary cleavage and carbon–carbon (C–C)bond secondary cleavage-based polymeric β-Lap prodrug(Azo-Lap NP) is designed, in which the self-immolated paraaminobenzyl linker is connected to poly(L-glutamic acid)(PGlu) via azo linkage and the responsive drug release of β-Lapagainst tumors can be achieved under high NAD(P)H:quinoneoxidoreductase 1 (NQO1) expression and low pH environmentin tumors. The effective covalent loading of β-Lap by Azo-LapNPs permitted a high administration dose of β-Lap and enabled significant tumor retention time. Moreover, Azo-LapNPs markedly reduced the side effects of β-Lap by avoidinghemolysis and the production of methemoglobin. The safety ofAzo-Lap NPs administration is validated in the antitumorexperiment of mice. In the 4T1 model, Azo-Lap NPs exhibiteda markedly higher tumor suppression rate than β-Lap. Thiswork provides an effective and safe polymeric prodrug fortumor selective delivery of β-Lap.

摘要：目的通过对中国人群踝关节形态学参数进行测量和统计分析,为踝关节置换术假体的设计提供理论基础和形态学数据支撑。方法模拟人工踝关节置换手术,对191例(男性106例、女性85例)踝关节CT影像数据行三维重建,重建图像测踝穴前后倾斜角(APA)、胫骨下端最大前后径(MTiTh)等32个形态学参数,并计算胫骨平均纵横比(MTiTh/TiW)和距骨平均纵横比(TaAL/TaW)等3项参数比。结果(1)所检验32个参数中有23个存在性别间差异(P<0.05),其中除踝穴前后倾斜角(APA)和踝穴前后距(APG)等3个参数外,其余20个参数为男大于女;(2)测量数据与之前本课题基于X线片结果比较,除踝穴前后距(APG)、踝穴前后倾斜角(APA)、胫骨远端滑车切迹长(TiAL)等3个参数外,其余8个参数均有显著性差异(P<0.05),且X线片大于CT;(3)由于种族与地域等的差异,中国正常成人踝关节三维形态学参数与法国、意大利、韩国、中国台湾人群等既往研究数据相比,数据之间存在差异;距骨体形态与埃及、希腊和华北地区人群存在差异。结论中国成人人群踝关节形态学参数与西方人群间存在差异。