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Exploring chitosan-shelled nanobubbles to improve HER2 + immunotherapy via dendritic cell targeting
Drug Delivery and Translational Research ( IF 5.7 ) Pub Date : 2022-06-07 , DOI: 10.1007/s13346-022-01185-8
Monica Argenziano 1 , Sergio Occhipinti 2 , Anna Scomparin 1 , Costanza Angelini 2 , Francesco Novelli 2 , Marco Soster 1 , Mirella Giovarelli 2 , Roberta Cavalli 1
Affiliation  

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.

Graphical abstract



中文翻译:

探索壳聚糖纳米气泡通过树突状细胞靶向改善 HER2+ 免疫治疗

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疗方法,包括免疫检查点抑制剂,存在一些局限性。树突状细胞疫苗接种已作为一种免疫治疗策略进行了研究,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,已经提出了许多纳米递送系统来促进癌症免疫治疗。这项工作旨在设计一种用于治疗 HER2 + 乳腺癌的新型免疫治疗纳米平台,并开发了专门定制的壳聚糖壳纳米气泡 (NBs),用于递送 DNA 疫苗。NB 已用抗 CD1a 抗体功能化以靶向树突状细胞 (DC)。NB 配方具有大约 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 NB 能够以良好的封装效率 (82%) 加载 DNA。抗 CD1a 功能化的 NB 旨在靶向 DC,并证明了在人和小鼠细胞模型中诱导 DC 活化的能力,并且还引发了能够减缓小鼠体内肿瘤生长的特异性免疫反应。这些发现证明了将肿瘤疫苗加载到靶向 DC 的壳聚糖纳米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。并且在 4 °C 下储存长达 6 个月时表现出良好的物理稳定性。体外表征已证实这些 NB 能够以良好的封装效率 (82%) 加载 DNA。抗 CD1a 功能化的 NB 旨在靶向 DC,并证明了在人和小鼠细胞模型中诱导 DC 活化的能力,并且还引发了能够减缓小鼠体内肿瘤生长的特异性免疫反应。这些发现证明了将肿瘤疫苗加载到靶向 DC 的壳聚糖纳米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。并且在 4 °C 下储存长达 6 个月时表现出良好的物理稳定性。体外表征已证实这些 NB 能够以良好的封装效率 (82%) 加载 DNA。抗 CD1a 功能化的 NB 旨在靶向 DC,并证明了在人和小鼠细胞模型中诱导 DC 活化的能力,并且还引发了能够减缓小鼠体内肿瘤生长的特异性免疫反应。这些发现证明了将肿瘤疫苗加载到靶向 DC 的壳聚糖纳米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。抗 CD1a 功能化的 NB 旨在靶向 DC,并证明了在人和小鼠细胞模型中诱导 DC 活化的能力,并且还引发了能够减缓小鼠体内肿瘤生长的特异性免疫反应。这些发现证明了将肿瘤疫苗加载到靶向 DC 的壳聚糖纳米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。抗 CD1a 功能化的 NB 旨在靶向 DC,并证明了在人和小鼠细胞模型中诱导 DC 活化的能力,并且还引发了能够减缓小鼠体内肿瘤生长的特异性免疫反应。这些发现证明了将肿瘤疫苗加载到靶向 DC 的壳聚糖纳米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。

图形概要

更新日期:2022-06-08
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