先前报道的金包铁氧化物纳米颗粒（Au-IONP's）已经显示出它们作为胰腺癌治疗药物传递载体的有效性，其携带了与热敏蒽二烯-Alder反应偶联链包含4个碳原子的链（TTLD4）的吉西他滨。通过激光照射Au-IONP's产生的热量促进了在突发释放曲线下的反 Diels-Alder 反应介导的释放，在180分钟内大约有一半的总释放量在前5分钟内发生。两个TTLD4的类似物，它们只在连接链长度（TTLD3和TTLD6）上有所不同，被合成并连接到Au-IONP's上。经过45℃的热介导释放实验证实，这些制剂中约有94%、76%和45%的TTLD3、TTLD4和TTLD6释放取决于连接链长度。Diels-Alder连结物的药物装载在5：1药物/Au-IONP的重量比中似乎倾向于含有偶数碳原子的TTLD4（76%）和TTLD6（57%）而非TTLD3（25%），可能是由于连接链可能处于与Au-IONP表面垂直的位置，因为存在着120℃C-C键。 版权所有 © 2023。由Elsevier B.V.出版。

Previously reported gold coated iron oxide nanoparticles (Au-IONP's) have demonstrated their effectiveness as drug delivery vehicles for gemcitabine conjugated to a thermally labile Diels-Alder linker containing a chain of 4 carbon atoms (TTLD4) for the treatment of pancreatic cancer. Heat generated via laser irradiation of Au-IONPs facilitated retro Diels-Alder mediated release in a burst release profile where approximately half of all total release over 180 min occurred within the first 5 min. Two analogues of TTLD4, which differ only in linker chain length (TTLD3 & TTLD6) were synthesised and conjugated to Au-IONP's. Heat-mediated release of gemcitabine at 45 ˚C over 180 min from these formulations was confirmed to be based on linker length, which was 94%, 76% and 45% for TTLD3, TTLD4 and TTLD6, respectively. Drug loading of the Diels-Alder linkers in a 5:1 Drug/Au-IONP w/w ratio appears to favour those containing an even number of carbons TTLD4 (76%) & TTLD6 (57%) over TTLD3 (25%), possibly due to the linker likely being positioned perpendicular to the Au-IONP surface because of the 120˚ C-C bond.Copyright © 2023. Published by Elsevier B.V.