含有阿霉素负载PLGA纳米颗粒和加热剂的肿瘤内温热化疗海藻酸钠水凝胶。
Intratumoral thermo-chemotherapeutic alginate hydrogel containing doxorubicin loaded PLGA nanoparticle and heating agent.
发表日期：2023 Aug 10
作者：
Li-Hui Tsai, Tai-Horng Young, Chia-Hsiang Yen, Wei-Cheng Yao, Chih-Hao Chang
来源：
Int J Biol Macromol
摘要：
化疗广泛应用于癌症治疗，然而化疗药物的非特异性全身毒性一直是一个问题。局部注射治疗是一种用来减少化疗药物不良反应的策略。此外，化疗药物与热疗联合使用可以进一步增强疗效。本研究制备了一种可注射的水凝胶，即阿霉素（DOX）负载的聚乳酸-羟基乳酸酸（PLGA）纳米粒（DPN）和在海藻酸水凝胶中嵌入的磁铁矿纳米粒（MNP）（DPN/MNP-HG）。DPN和MNP分别是化疗和加热的药物，在肿瘤内热疗和化疗中起到作用。可注射的DPN/MNP-HG在室温下通过离子交联便捷制备，具有固体弹性特性。当暴露于交变磁场（AMF）下时，DPN/MNP-HG表现出可控的热产生，并呈可逆的温度升高曲线。在DOX释放的动力学研究中，DPN/MNP-HG在有和无AMF的情况下均呈现出缓慢的初始释放和持续释放特性。在细胞毒性研究和皮下小鼠癌症模型中，成功使用DPN/MNP-HG进行热疗和化疗，导致细胞存活率显著降低和肿瘤生长抑制增加；小鼠对注射的DPN/MNP-HG在有(+)和无AMF应用的情况下均表现出良好的耐受性。综上所述，提出的适用于局部肿瘤内注射的热疗和化疗DPN/MNP-HG是一种有前景的癌症治疗制剂。(c)2023 Elsevier B.V. All rights reserved.
Chemotherapy has been widely used to treat cancer; however, the non-specific systemic toxicity of chemotherapeutic agents has always been an issue. Local injection treatment is a strategy used to reduce the undesired adverse effects of chemotherapeutic drugs. In addition, chemotherapeutic agents combined with thermotherapy are effective in further enhancing therapeutic potency. In the present study, we prepared an injectable hydrogel, namely, doxorubicin (DOX)-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticle (DPN) and magnetite nanoparticle (MNP) embedded in alginate hydrogel (DPN/MNP-HG), where DPN and MNP were the chemotherapeutic and heating agents, respectively, for intratumoral thermo-chemotherapy. Injectable DPN/MNP-HG, which possesses solid-like elastic properties, was conveniently prepared via ionic cross-linking at room-temperature. When exposed to an alternating magnetic field (AMF), DPN/MNP-HG exhibited controllable heat generation with a reversible temperature-rise profile. Regarding the kinetics of DOX release, both with and without AMF, DPN/MNP-HG exhibited a slow initial burst and sustained release profile. In cytotoxicity studies and subcutaneous mouse cancer models, successful thermo-chemotherapy with DPN/MNP-HG resulted in significantly lower cell viability and increased tumor-growth suppression; mice also exhibited good tolerance to injected DPN/MNP-HG both with(+) and without AMF application. In conclusion, the proposed thermo-chemotherapeutic DPN/MNP-HG for local intratumoral injection is a promising formulation for cancer treatment.Copyright © 2023. Published by Elsevier B.V.