Injectable and Multifunctional Hydrogels Based on Poly(N-acryloyl glycinamide) and Alginate Derivatives for Antitumor Drug Delivery,ACS Applied Materials & Interfaces

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Injectable and Multifunctional Hydrogels Based on Poly(N-acryloyl glycinamide) and Alginate Derivatives for Antitumor Drug Delivery
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2024-03-12 , DOI: 10.1021/acsami.4c00298
Trung Thang Vu ₁ , Sung-Han Jo ₂ , Seon-Hwa Kim ₂ , Byeong Kook Kim ₂ , Sang-Hyug Park ₂ , Kwon Taek Lim _{1,

3}

Affiliation

Chemotherapy is a conventional treatment that uses drugs to kill cancer cells; however, it may induce side effects and may be incompletely effective, leading to the risk of tumor recurrence. To address this issue, we developed novel injectable thermal/near-infrared (NIR)-responsive hydrogels to control drug release. The injectable hydrogel formulation was composed of biocompatible alginates, poly(N-acryloyl glycinamide) (PNAGA) copolymers with an upper critical solution temperature, and NIR-responsive cross-linkers containing coumarin groups, which were gelated through bioorthogonal inverse electron demand Diels–Alder reactions. The hydrogels exhibited quick gelation times (120–800 s) and high drug loading efficiencies (>90%). The hydrogels demonstrated a higher percentage of drug release at 37 °C than that at 25 °C due to the enhanced swelling behavior of temperature-responsive PNAGA moieties. Upon NIR irradiation, the hydrogels released most of the entrapped doxorubicin (DOX) (97%) owing to the cleavage of NIR-sensitive coumarin ester groups. The hydrogels displayed biocompatibility with normal cells, while induced antitumor activity toward cancer cells. DOX/hydrogels treated with NIR light inhibited tumor growth in nude mice bearing tumors. In addition, the injected hydrogels emitted red fluorescence upon excitation at a green wavelength, so that the drug delivery and hydrogel degradation in vivo could be tracked in the xenograft model.

中文翻译：

基于聚（N-丙烯酰甘氨酰胺）和海藻酸盐衍生物的可注射多功能水凝胶，用于抗肿瘤药物输送

化疗是一种使用药物杀死癌细胞的传统治疗方法。然而，它可能会引起副作用，并且可能不完全有效，导致肿瘤复发的风险。为了解决这个问题，我们开发了新型可注射热/近红外（NIR）响应水凝胶来控制药物释放。可注射水凝胶配方由生物相容性海藻酸盐、具有上限临界溶液温度的聚( N-丙烯酰甘氨酰胺) (PNAGA) 共聚物和含有香豆素基团的近红外响应交联剂组成，通过生物正交逆电子需求 Diels-Alder 凝胶化反应。该水凝胶表现出快速的凝胶时间（120-800 s）和高的载药效率（> 90％）。由于温度响应性 PNAGA 部分的溶胀行为增强，水凝胶在 37°C 下的药物释放百分比高于 25°C 下的药物释放百分比。在近红外辐射下，由于近红外敏感香豆素酯基团的裂解，水凝胶释放了大部分捕获的阿霉素 (DOX) (97%)。水凝胶表现出与正常细胞的生物相容性，同时诱导对癌细胞的抗肿瘤活性。用近红外光处理的 DOX/水凝胶抑制荷瘤裸鼠的肿瘤生长。此外，注射的水凝胶在绿色波长激发下发出红色荧光，因此可以在异种移植模型中跟踪体内药物输送和水凝胶降解。

更新日期：2024-03-12

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