Particles made of a novel recombinant spider silk protein rAcSp2 as delivery system for peptide drugs with anti-tumor activity

IF 3.7 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Fengman Han , Xianglong Li , Yu Tan , Qingyu Zhou
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引用次数: 0

Abstract

The recombinant spider silk proteins (spidroins) are promising biomaterials for the use as drug delivery system (DDS) because of their non-cytotoxicity, low immunogenicity and customizable properties. However, most reported spidroin-based materials as DDS derive from the repetitive domain of dragline silk protein, limiting us to take advantage of their desirable properties for medical and industrial innovation. Here, we produced the recombinant aciniform silk protein (rAcSp2) that contains only the N-terminal domain and formulated it into nanoparticles for use as a DDS. We demonstrated that antitumor peptide drugs such as ChMAP-28 can be loaded onto rAcSp2 particles via electrostatic interaction, with a high loading capacity of up to 45 % (w/w) and nearly 100 % loading efficiency. In addition, the release of ChMAP-28 depends on the pH and ionic strength of the release buffer. In the meantime, rAcSp2 particles not only effectively reduce the toxicity of ChMAP-28 to normal cells, but also significantly enhance its anti-tumor activity. Therefore, our rAcSp2 particles are a promising novel particulate drug carrier system for the delivery of peptide drugs with anti-tumor activity.
用新型重组蜘蛛丝蛋白 rAcSp2 制成的颗粒作为具有抗肿瘤活性的多肽药物的递送系统
重组蛛丝蛋白(spidroins)具有无细胞毒性、低免疫原性和可定制的特性,是一种很有希望用作药物输送系统(DDS)的生物材料。然而,大多数已报道的基于螺旋藻蛋白的 DDS 材料都来自龙蚕丝蛋白的重复结构域,这限制了我们利用其理想特性进行医疗和工业创新。在这里,我们制备了仅含有 N 端结构域的重组刺丝蛋白(rAcSp2),并将其配制成纳米颗粒用作 DDS。我们证明了 ChMAP-28 等抗肿瘤多肽药物可通过静电作用负载到 rAcSp2 颗粒上,负载能力高达 45%(重量比),负载效率接近 100%。此外,ChMAP-28 的释放取决于释放缓冲液的 pH 值和离子强度。同时,rAcSp2 颗粒不仅能有效降低 ChMAP-28 对正常细胞的毒性,还能显著增强其抗肿瘤活性。因此,我们的 rAcSp2 颗粒是一种很有前景的新型颗粒载药系统,可用于递送具有抗肿瘤活性的多肽药物。
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来源期刊
Biochemical Engineering Journal
Biochemical Engineering Journal 工程技术-工程:化工
CiteScore
7.10
自引率
5.10%
发文量
380
审稿时长
34 days
期刊介绍: The Biochemical Engineering Journal aims to promote progress in the crucial chemical engineering aspects of the development of biological processes associated with everything from raw materials preparation to product recovery relevant to industries as diverse as medical/healthcare, industrial biotechnology, and environmental biotechnology. The Journal welcomes full length original research papers, short communications, and review papers* in the following research fields: Biocatalysis (enzyme or microbial) and biotransformations, including immobilized biocatalyst preparation and kinetics Biosensors and Biodevices including biofabrication and novel fuel cell development Bioseparations including scale-up and protein refolding/renaturation Environmental Bioengineering including bioconversion, bioremediation, and microbial fuel cells Bioreactor Systems including characterization, optimization and scale-up Bioresources and Biorefinery Engineering including biomass conversion, biofuels, bioenergy, and optimization Industrial Biotechnology including specialty chemicals, platform chemicals and neutraceuticals Biomaterials and Tissue Engineering including bioartificial organs, cell encapsulation, and controlled release Cell Culture Engineering (plant, animal or insect cells) including viral vectors, monoclonal antibodies, recombinant proteins, vaccines, and secondary metabolites Cell Therapies and Stem Cells including pluripotent, mesenchymal and hematopoietic stem cells; immunotherapies; tissue-specific differentiation; and cryopreservation Metabolic Engineering, Systems and Synthetic Biology including OMICS, bioinformatics, in silico biology, and metabolic flux analysis Protein Engineering including enzyme engineering and directed evolution.
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