Triple negative breast cancer patients remain with chemotherapy as their only viable therapeutic option. However, the toxicity of available anticancer drugs and their inefficient delivery have limited the development of effective chemotherapy administration protocols and combination therapies. Drug delivery devices that can properly target chemotherapy to the right cells with efficient cancer-cell killing may play a vital role in eliminating triple-negative breast cancer. While systemic delivery results in low drug accumulation at the tumor site and for a short period of time, local delivery enables sustained drug release. However, a system that is able to provide rapid, yet prolonged action, would enable efficient tumor elimination. Herein, the development of dual-sensitive nanogels is described that are designed to rapidly dislodge the chemotherapy drug, doxorubicin, inside cancer cells through dual-sensitive action-pH and redox sensitivities-enabling efficient cancer-cell killing while eliminating systemic side effects. Their embedding within a hydrogel injected next to a tumor in a triple-negative breast-cancer mouse model enables prolonged release of the drug with instantaneous action when inside the cells resulting in efficacious tumor elimination compared to sustained local delivery only. This technology can be used for the delivery of combination therapies and for the treatment of other solid tumors.

中文翻译：

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刺激性纳米凝胶在三阴性乳腺癌细胞中快速释放阿霉素的长时间局部体内递送。

三阴性乳腺癌患者仍将化疗作为其唯一可行的治疗选择。然而，可用的抗癌药的毒性及其低效的递送限制了有效化学疗法给药方案和联合疗法的开发。可以将化疗正确地靶向正确的细胞并有效杀死癌细胞的给药装置，在消除三阴性乳腺癌中可能起着至关重要的作用。虽然全身递送导致在肿瘤部位和短时间内的低药物蓄积，但是局部递送使得药物能够持续释放。然而，能够提供快速但延长的作用的系统将能够有效消除肿瘤。在这里 描述了双敏感纳米凝胶的开发，该纳米凝胶旨在通过双敏感作用pH和氧化还原敏感度快速将化疗药物多柔比星移入癌细胞内部，从而有效杀死癌细胞，同时消除系统性副作用。与仅持续局部递送相比，它们在三阴性乳腺癌小鼠模型中嵌入肿瘤旁注射的水凝胶中，能够在细胞内部以瞬时作用延长药物的释放，从而有效消除肿瘤。该技术可以用于联合疗法的递送和其他实体瘤的治疗。与仅持续局部递送相比，它们在三阴性乳腺癌小鼠模型中嵌入肿瘤旁注射的水凝胶中，能够在细胞内部以瞬时作用延长药物的释放，从而有效消除肿瘤。该技术可以用于联合疗法的递送和其他实体瘤的治疗。与仅持续局部递送相比，它们在三阴性乳腺癌小鼠模型中嵌入肿瘤旁注射的水凝胶中，能够在细胞内部以瞬时作用延长药物的释放，从而有效消除肿瘤。该技术可以用于联合疗法的递送和其他实体瘤的治疗。