Optimized silk fibroin nanoparticle functionalization with anti-CEA nanobody enhancing active targeting of colorectal cancer cells

丝素 盐酸阿霉素 生物相容性 材料科学 药物输送 纳米颗粒 表面改性 纳米技术 细胞毒性 生物物理学 阿霉素 体外 化学 生物化学 丝绸 生物 化疗 物理化学 冶金 复合材料 遗传学
作者
Xiying Fan,Xinying Peng,Tingting Wang,Yi Gu,Guochuan Sun,Qinghui Shou,Haipeng Song,Rui Nian,Wenshuai Liu
出处
期刊:Biomedical Materials [IOP Publishing]
卷期号:18 (4): 045027-045027
标识
DOI:10.1088/1748-605x/acdeba
摘要

Abstract This work aimed to establish a simple and feasible method to obtain silk fibroin nanoparticles (SFNPs) with uniform particles size, and then modify the SFNPs with nanobody (Nb) 11C12 targeting the proximal membrane end of carcinoembryonic antigen on the surface of colorectal cancer (CRC) cells. The regenerated silk fibroin (SF) was isolated using ultrafiltration tubes with a 50 kDa molecular weight cut-off, and the retention fraction (named as SF > 50 kDa) was further self-assembled into SFNPs by ethanol induction. Scanning electron microscope (SEM) and high-resolution transmission electron microscop showed that the SFNPs with uniform particles size were formed. Due to electrostatic adsorption and pH responsiveness, SFNPs have been proved to effectively load and release the anticancer drug doxorubicin hydrochloride (DOX) (DOX@SFNPs). Further, targeting molecule Nb 11C12 was used to modify these nanoparticles, constituting the targeted outer layer of the drug delivery system (DOX@SFNPs-11C12), achieving precise localization to cancer cells. The release amount of DOX observed from in vitro drug release profiles increased as follows: pH 7.4 < pH 6.8 < pH 5.4, demonstrating that the DOX release could be accelerated in a weakly acidic environment. In vitro cytotoxicity experiments displayed that SFNPs-11C12 nanoparticles exhibited good safety and biocompatibility. Drug-loaded nanoparticles, DOX@SFNPs-11C12, led to higher LoVo cells apoptosis compared to DOX@SFNPs. Fluorescence spectrophotometer characterization and confocal laser scanning microscopy further showed that the internalization of DOX was highest in the DOX@SFNPs-11C12, certifying that the introduced targeting molecule enhanced the uptake of drug delivery system by LoVo cells. This study provides a simple and operational approach to developing an optimized SFNPs drug delivery system modified by targeting Nb, which can be a good candidate for CRC therapy.
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