使用氢氧化钠（NaOH）注射的高碱处理可以成为杀死肿瘤细胞的治疗方法。碱化会损害细胞结构并导致细胞死亡。增加碱度还可以增强某些化疗药物的疗效，例如阿霉素 (DOX)。在这项研究中，负载NaOH的淀粉植入物（NST植入物）被用来诱导肿瘤环境中的高碱化（增加pH值），从而诱导坏死并增强DOX的作用。 NaOH 是一种强碱性物质，注射到肿瘤中可以增加 pH 值。然而，使用 NaOH 可能会产生毒副作用，因为它会增加整个身体的 pH 值，而不仅仅是肿瘤部位的 pH 值。为了克服这个问题，我们开发了一种可注射的 NST 植入物，其中 NaOH 可以直接输送到肿瘤中。这项研究表明，NST 植入物可以很容易地在携带 4T1 肿瘤的小鼠体内进行瘤内给药，并且 NST 植入物释放的大部分 NaOH 都被输送到肿瘤。虽然 NST 植入物中的一些 NaOH 可以被全身吸收，但它会被人体的缓冲效应中和，从而降低毒性风险。这项研究还在体外和体内证实，DOX 在碱化时更能有效地杀死 4T1 细胞。研究表明，注射 NST 植入物后给予 DOX 可以杀死大多数肿瘤。使用 NST 植入物向肿瘤输送 NaOH 可以减少全身吸收和副作用。此外，NST植入物诱导的碱化不仅发挥抗癌作用，还可以增强DOX杀死癌细胞的效果。因此，负载 NaOH 的淀粉植入物与 DOX 治疗相结合有可能成为一种新型肿瘤疗法。© 2023 沉阳药科大学。由 Elsevier B.V. 出版

High-alkali treatment using sodium hydroxide (NaOH) injection can be a therapeutic approach for killing tumor cells. Alkalization can damage cellular structures and lead to cell death. Increased alkalinity can also enhance the efficacy of certain chemotherapeutic drugs such as doxorubicin (DOX). In this study, NaOH-loaded starch implants (NST implants) were used to induce hyperalkalization (increase pH) in the tumor environment, thereby inducing necrosis and enhancing the effects of DOX. NaOH is a strongly alkaline substance that can increase the pH when injected into a tumor. However, the administration of NaOH can have toxic side effects because it increases the pH of the entire body, not just at the tumor site. To overcome this problem, we developed an injectable NST implant, in which NaOH can be delivered directly into the tumor. This study showed that NST implants could be easily administered intratumorally in mice bearing 4T1 tumors and that most of the NaOH released from the NST implants was delivered to the tumors. Although some NaOH from NST implants can be systemically absorbed, it is neutralized by the body's buffering effect, thereby reducing the risk of toxicity. This study also confirmed both in vitro and in vivo that DOX is more effective at killing 4T1 cells when alkalized. It has been shown that administration of DOX after injection of an NST implant can kill most tumors. Systemic absorption and side effects can be reduced using an NST implant to deliver NaOH to the tumor. In addition, alkalinization induced by NST implants not only exerts anticancer effects but can also enhance the effect of DOX in killing cancer cells. Therefore, the combination of NaOH-loaded starch implants and DOX treatment has the potential to be a novel therapy for tumors.© 2023 Shenyang Pharmaceutical University. Published by Elsevier B.V.