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用于原位光热/内分泌协同治疗子宫内膜异位症的具有近红外控制药物递送功能的可注射水凝胶纳米结构

Injectable hydrogel nanoarchitectonics with near-infrared controlled drug delivery for in situ photothermal/endocrine synergistic endometriosis therapy.

作者信息

Tian Wei, Wang Chenyu, Chu Ran, Ge Haiyan, Sun Xiao, Li Mingjiang

机构信息

Department of Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.

School of Chemistry and Pharmaceutical Engineering, Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

出版信息

Biomater Res. 2023 Oct 7;27(1):100. doi: 10.1186/s40824-023-00442-2.

Abstract

BACKGROUND

Endometriosis is a common gynecological disease in women of childbearing age. Commonly used treatment methods, such as endocrine and surgical therapies, display poor therapeutic effects with a high relapse probability. Thus, novel treatments for endometriosis are required.

METHODS

In our study, polydopamine (PDA), letrozole (LTZ), and agarose (AG) hydrogels were combined to construct an injectable hydrogel with near-infrared controlled drug delivery named LTZ-PDA@AG hydrogel for endometriosis treatment. The release of letrozole can be accurately controlled by the near-infrared light intensity, exposure duration, polydopamine concentration, and hydrogel composition. Meanwhile, we isolated endometrial stromal cells from endometrium in patients with endometriosis, and constructed the rats' model of endometriosis to verify the biological effects of LTZ-PDA@AG hydrogel.

RESULTS

Owing to the sufficiently deep penetration of near-infrared light, the LTZ-PDA@AG hydrogel displayed a high temperature increase for efficient photothermal therapy. In addition, high local temperatures can further enhance the diffusion and penetration of letrozole, thereby achieving excellent therapeutic effect in vivo. Importantly, the in vivo and vitro test demonstrated the capacity of the nanocomposite hydrogel for endocrine-photothermal synergistic therapy and the biocompatibility.

CONCLUSION

Our work proposes a novel concept for precision endometriosis therapy by photothermal-enhanced endocrine therapy for endometriosis, which is proposed for the first time for the treatment of endometriosis and demonstrates excellent potential for further clinical translation.

TRIAL REGISTRATION

Not applicable. LTZ-PDA@AG hydrogels were synthesized and displayed a high temperature increase for efficient photothermal therapy under NIR. The present study shows the capacity of the nanocomposite hydrogel for endocrine-photothermal synergistic therapy and the biocompatibility.

摘要

背景

子宫内膜异位症是育龄期女性常见的妇科疾病。常用的治疗方法,如内分泌和手术治疗,疗效不佳且复发概率高。因此,需要新的子宫内膜异位症治疗方法。

方法

在我们的研究中,将聚多巴胺(PDA)、来曲唑(LTZ)和琼脂糖(AG)水凝胶结合,构建了一种用于子宫内膜异位症治疗的具有近红外控释药物功能的可注射水凝胶,即LTZ-PDA@AG水凝胶。来曲唑的释放可通过近红外光强度、照射持续时间、聚多巴胺浓度和水凝胶组成精确控制。同时,我们从子宫内膜异位症患者的子宫内膜中分离出子宫内膜基质细胞,并构建了子宫内膜异位症大鼠模型,以验证LTZ-PDA@AG水凝胶的生物学效应。

结果

由于近红外光具有足够深的穿透性,LTZ-PDA@AG水凝胶表现出高温升高,可实现高效的光热治疗。此外,局部高温可进一步增强来曲唑的扩散和渗透,从而在体内实现优异的治疗效果。重要的是,体内和体外试验证明了该纳米复合水凝胶具有内分泌-光热协同治疗能力和生物相容性。

结论

我们的工作提出了一种通过光热增强内分泌疗法治疗子宫内膜异位症的精准治疗新观念,这是首次提出用于治疗子宫内膜异位症,并显示出进一步临床转化的巨大潜力。

试验注册

不适用。LTZ-PDA@AG水凝胶已合成,并在近红外光下表现出高温升高以实现高效光热治疗。本研究展示了该纳米复合水凝胶的内分泌-光热协同治疗能力和生物相容性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82c8/10560439/6a008b3e34f4/40824_2023_442_Sch1_HTML.jpg

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