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靶向膜结合热休克蛋白70用于癌症治疗的核壳型壳聚糖颗粒

Core-Shell Chitosan Particles Targeting Membrane-Bound Heat Shock Protein 70 for Cancer Therapy.

作者信息

Svirshchevskaya Elena V, Kostenko Valentina V, Boyko Anna A, Shevtsov Maxim, Kholodenko Roman V, Grechikhina Maria V, Gracheva Iuliia A, Fedorov Alexey Yu, Sapozhnikov Alexander M

机构信息

Laboratory of Cell Interactions, Department of Immunology, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, 117997 Moscow, Russia.

Department of Radiation Oncology, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany.

出版信息

Nanomaterials (Basel). 2024 Nov 22;14(23):1873. doi: 10.3390/nano14231873.

Abstract

Anti-cancer targeted therapy is a promising approach. However, the identification of target molecules over-expressed in a wide range of tumors remains a significant challenge. The aim of this study was to analyze the expression of cell membrane-exposed heat shock protein 70 kDa (mHSP70) on different tumor cells and to develop a nanoscale delivery system based on a monoclonal antibody (mAb) that recognizes mHSP70 and uses chitosan core-shell nanoparticles (NPs). Several types of tumor cells (breast, pancreas, colon, prostate cancers, and some lymphomas) expressed mHSP70 as was determined by flow cytometry and confocal microscopy both in 2D and 3D cultures. Core NPs were formed by chitosan (C) conjugated to allocolchicinoid, which was used as a model drug (D). mAbs (A) targeting mHSP70 were complexed with succinylchitosan and used as NP shells forming final CAD-NPs. These NPs were characterized by size, charge, and functional activity. CAD-NPs were shown to have additional toxicity in comparison with CD-NPs in mHSP7-positive cells. Taken collectively, this study shows that mAb to mHSP70 can be used as a targeting vector in antitumor therapy.

摘要

抗癌靶向治疗是一种很有前景的方法。然而,鉴定在多种肿瘤中过度表达的靶分子仍然是一项重大挑战。本研究的目的是分析不同肿瘤细胞上细胞膜暴露的70 kDa热休克蛋白(mHSP70)的表达情况,并开发一种基于识别mHSP70的单克隆抗体(mAb)并使用壳聚糖核壳纳米颗粒(NPs)的纳米级递送系统。通过流式细胞术和共聚焦显微镜在二维和三维培养中均确定,几种类型的肿瘤细胞(乳腺癌、胰腺癌、结肠癌、前列腺癌和一些淋巴瘤)表达mHSP70。核心纳米颗粒由与别秋水仙碱类结合的壳聚糖(C)形成,别秋水仙碱类用作模型药物(D)。靶向mHSP70的单克隆抗体(A)与琥珀酰壳聚糖复合,并用作形成最终CAD纳米颗粒的纳米颗粒外壳。这些纳米颗粒通过大小、电荷和功能活性进行表征。与mHSP7阳性细胞中的CD纳米颗粒相比,CAD纳米颗粒显示出额外的毒性。总体而言,本研究表明,针对mHSP70的单克隆抗体可作为抗肿瘤治疗中的靶向载体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d28/11643800/7a67da94efe4/nanomaterials-14-01873-g001.jpg

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