下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:Exploring chitosan-shelled nanobubbles to improve HER2 + immunotherapy via dendritic cell targeting.
NB制剂尺寸约为300 nm,表面带正电荷,并且在4 °C下储存长达6个月时显示出良好的物理稳定性。
免疫疗法是一种有价值的癌症治疗方法,因为它能够激活免疫系统。然而,目前临床实践中的治愈性方法,包括免疫检查点抑制剂,存在一些局限性。树突状细胞疫苗已被研究作为一种免疫治疗策略,而基于纳米技术的递送系统已成为改善免疫治疗和疫苗开发的有力工具。因此,许多纳米递送系统已被提出用于促进癌症免疫治疗。本研究旨在设计一种纳米递送系统,并开发了专门定制的壳聚糖纳米气泡(NBs)用于递送DNA疫苗。这些NBs已通过抗CD1a抗体进行功能化以靶向树突状细胞(DCs)。NB制剂具有约300 nm的尺寸和正表面电荷,并且在4 °C下储存长达6个月时也表现出良好的物理稳定性。体外表征已证实这些NBs能够以良好的包封效率(82%)装载DNA。抗CD1a功能化的NBs被设计用于靶向DCs,并在人类和小鼠细胞模型中证明了诱导DC激活的能力,还引发了能够减缓小鼠体内肿瘤生长的特异性免疫反应。这些发现是概念验证,即把肿瘤疫苗装载到靶向DC的壳聚糖纳米气泡中可能成为未来癌症免疫治疗的一种有吸引力的纳米技术方法。
Immunotherapy is a valuable approach to cancer treatment as it is able to activate the immune system. However, the curative methods currently in clinical practice, including immune checkpoint inhibitors, present some limitations. Dendritic cell vaccination has been investigated as an immunotherapeutic strategy, and nanotechnology-based delivery systems have emerged as powerful tools for improving immunotherapy and vaccine development. A number of nanodelivery systems have therefore been proposed to promote cancer immunotherapy. This work aims to design a novel immunotherapy nanoplatform for the treatment of HER2 + breast cancer, and specially tailored chitosan-shelled nanobubbles (NBs) have been developed for the delivery of a DNA vaccine. The NBs have been functionalized with anti-CD1a antibodies to target dendritic cells (DCs). The NB formulations possess dimensions of approximately 300 nm and positive surface charge, and also show good physical stability up to 6 months under storage at 4 °C. In vitro characterization has confirmed that these NBs are capable of loading DNA with good encapsulation efficiency (82%). The antiCD1a-functionalized NBs are designed to target DCs, and demonstrated the ability to induce DC activation in both human and mouse cell models, and also elicited a specific immune response that was capable of slowing tumor growth in mice in vivo. These findings are the proof of concept that loading a tumor vaccine into DC-targeted chitosan nanobubbles may become an attractive nanotechnology approach for the future immunotherapeutic treatment of cancer.
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