Aminopeptidase N-Responsive Conjugates with Tunable Charge-Reversal Properties for Highly Efficient Tumor Accumulation and Penetration

Tumor enzyme-responsive charge-reversal carriers can induce efficient transcytosis and lead to efficient tumor infiltration and potent anticancer efficacy. However, the correlations of molecular structure with charge-reversal property, tumor penetration, and drug delivery efficiency are unknown. Herein, aminopeptidase N (APN)-responsive conjugates were synthesized to investigate these correlations. We found that the monomeric unit structure and the polymer chain structure determined the enzymatic hydrolysis and charge-reversal rates, and accordingly, the transcytosis and tumor accumulation and penetration of the APN-responsive conjugates. The conjugate with moderate APN responsiveness balanced the in vitro transcytosis and in vivo overall drug delivery process and achieved the best tumor delivery efficiency, giving potent antitumor efficacy. This work provides new insight into the design of tumor enzyme-responsive charge-reversal nanomedicines for efficient cancer drug delivery.     

应变幅值对循环载荷下NiTi合金力学性质的影响

实验研究了应变幅值对循环载荷下NiTi合金伪弹性退化特征的影响规律,结果表明:当卸载发生在NiTi合金应力诱发马氏体相变阶段时,应变幅值对马氏体相变开始应力的退化规律影响较小,但此时应变幅值的增加会显著增大奥氏体弹性模量的退化程度,而其大变形可回复能力和阻尼特性在应变幅值大于6%时才有大幅度降低。对各参数退化程度进行定量分析,得到了NiTi合金具有较强可回复能力和阻尼性能的应变幅值范围。该研究可为NiTi合金阻尼器的设计提供参考。