<br>可编程 DNA 水凝胶辅助微晶制剂在手术残留肿瘤病变和淋巴结转移中持续局部药物递送,Advanced Healthcare Materials

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可编程 DNA 水凝胶辅助微晶制剂在手术残留肿瘤病变和淋巴结转移中持续局部药物递送
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2023-12-04 , DOI: 10.1002/adhm.202303762
Zi-Jie Zhang _{1,

2,

3} , Yi Zhou ₂ , Huan Tong ₄ , Xi-Cheng Sun ₂ , Zi-Cheng Lv ₂ , June-Kong Yong ₂ , Yi-Chi Wu ₂ , Xue-Lin Xiang ₂ , Fei Ding ₂ , Xiao-Lei Zuo _{3,

5} , Fan Li _{3,

5} , Qiang Xia _{1,

2,

3} , Hao Feng _{1,

2,

3} , Chun-Hai Fan ₂

Affiliation

手术残留肿瘤病灶（手术R1切除（如肝癌浸润膈肌、手术残留乳腺癌、术后残留卵巢癌）或消融后边界残留）及无法手术切除的淋巴结转移（腹膜后淋巴结）明显影响肿瘤患者术后生存。这一临床难题给局部药物输送系统带来了三大挑战：稳定持续的输送、良好的生物相容性以及包装可与其他治疗协同的新靶向药物的能力。在此，报道了一种由纯 DNA 链生成的载药水凝胶，并且在调整其网格尺寸方面具有高度可编程性。同时，DNA水凝胶可以辅助新型放射增敏药物、共济失调性毛细血管扩张症和rad3相关蛋白（ATR）抑制剂（Elimusertib）的微结晶，进一步促进其长期释放。当应用于肿瘤部位时，水凝胶系统表现出显着的抗肿瘤活性，最大限度地降低全身毒性，并对肿瘤-免疫细胞界面具有调节作用。这种载药 DNA 水凝胶平台代表了一种对手术残留肿瘤病灶和淋巴结转移患者进行辅助治疗的新方式。

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Programmable DNA Hydrogel Assisting Microcrystal Formulations for Sustained Locoregional Drug Delivery in Surgical Residual Tumor Lesions and Lymph Node Metastasis

Surgical residual tumor lesions (R1 resection of surgical procedures (e.g., liver cancer infiltrating the diaphragm, surgical residual breast cancer, postoperative residual ovarian cancer) or boundary residual after ablation) and lymph node metastasis that cannot be surgically resected (retroperitoneal lymph nodes) significantly affect postoperative survival of tumor patients. This clinical conundrum poses three challenges for local drug delivery systems: stable and continuous delivery, good biocompatibility, and the ability to package new targeted drugs that can synergize with other treatments. Here, a drug-laden hydrogel generated from pure DNA strands and highly programmable in adjusting its mesh size is reported. Meanwhile, the DNA hydrogel can assist the microcrystallization of novel radiosensitizing drugs, ataxia telangiectasia and rad3-related protein (ATR) inhibitor (Elimusertib), further facilitating its long-term release. When applied to the tumor site, the hydrogel system demonstrates significant antitumor activity, minimized systemic toxicity, and has a modulatory effect on the tumor-immune cell interface. This drug-loaded DNA-hydrogel platform represents a novel modality for adjuvant therapy in patients with surgical residual tumor lesions and lymph node metastasis.

更新日期：2023-12-04

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