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叶酸修饰的牛血清白蛋白包裹的载双药中空介孔二氧化硅纳米粒的制备,用于胃癌治疗的pH响应性靶向递送

Fabrication of folic acid-modified bovine serum albumin cloaked dual-drug loaded hollow mesoporous silica nanoparticles for pH-responsive and targeted delivery of gastric cancer therapy.

作者信息

Zhang Yuanwei, Liang Yuanxiao

机构信息

Shengzhou Branch of Zhejiang University First Hospital, Shengzhou People's Hospital, Shengzhou, 312400, China.

Xinchang County People's Hospital, Xinchang, 312500, China.

出版信息

Heliyon. 2024 Apr 7;10(8):e29274. doi: 10.1016/j.heliyon.2024.e29274. eCollection 2024 Apr 30.

DOI:10.1016/j.heliyon.2024.e29274
PMID:38699737
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11063411/
Abstract

Combination therapy is a highly successful way to address the limitations of using a single treatment method and improve therapy's overall efficacy. In this study, we developed a unique hollow mesoporous silica nanoparticle (HMSN) coated with folic acid (FA)-modified bovine serum albumin (FA-BSA). This nanoparticle, referred to as HFB, was designed to target cancer cells and release dual therapeutic drugs, Indocyanine green (ICG) and Paclitaxel (PTX), in response to specific stimuli termed as HFB@IP. The BSA protein acts as a "gatekeeper" to prevent early drug releases and cargo leakage by detaching from BSA in reaction to GSH. The FA facilitates the targeted transport of the drug into cancer cells that express folate receptors (FR), enhancing the effectiveness of chemo-photodynamic treatment (PDT). The drug nanocarrier demonstrated in vitro pH/redox-triggered drug release from HFB@IP due to breaking the imine bonds between aldehyde-functionalized HMSN (CHO-HMSN) and FA-BSA with the disulfide bond inside BSA. In addition, various biological assessments, including cell uptake experiments, demonstrated that HFB@IP effectively targets SGC-7901 cells and induces apoptosis in vitro. Further, it exhibits remarkable efficiency in synergistically killing cancer cells through chemo-photodynamic therapy, as indicated by a combination index (CI) of 0.328. The results showed that combining HMSN with biodegradable stimuli-responsive BSA molecules could offer a promising approach for precise chemo-photodynamic therapy in treating gastric cancer, allowing for the controlled release of drugs as necessary.

摘要

联合治疗是一种非常成功的方法,可以解决单一治疗方法的局限性并提高治疗的整体疗效。在本研究中,我们开发了一种独特的中空介孔二氧化硅纳米颗粒(HMSN),其表面包覆有叶酸(FA)修饰的牛血清白蛋白(FA-BSA)。这种纳米颗粒,称为HFB,旨在靶向癌细胞,并响应特定刺激释放两种治疗药物,吲哚菁绿(ICG)和紫杉醇(PTX),称为HFB@IP。BSA蛋白充当“守门人”,通过与谷胱甘肽反应从BSA上脱离来防止药物过早释放和货物泄漏。FA促进药物靶向运输到表达叶酸受体(FR)的癌细胞中,增强化学光动力治疗(PDT)的有效性。由于破坏了醛基功能化的HMSN(CHO-HMSN)与FA-BSA之间的亚胺键以及BSA内部的二硫键,药物纳米载体在体外表现出pH/氧化还原触发的从HFB@IP释放药物。此外,包括细胞摄取实验在内的各种生物学评估表明,HFB@IP有效地靶向SGC-7901细胞并在体外诱导细胞凋亡。此外,如联合指数(CI)为0.328所示,它在通过化学光动力疗法协同杀死癌细胞方面表现出显著的效率。结果表明,将HMSN与可生物降解的刺激响应性BSA分子相结合,可以为胃癌的精确化学光动力治疗提供一种有前景的方法,允许根据需要控制药物释放。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e91e/11063411/0a56a68e4073/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e91e/11063411/bea7e8c25ea9/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e91e/11063411/6049efe2ff4e/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e91e/11063411/11dbf8883ee3/gr3.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e91e/11063411/dd3f88b6aafb/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e91e/11063411/2e232246739c/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e91e/11063411/2b55f59bd245/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e91e/11063411/eebbcd989e48/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e91e/11063411/0a56a68e4073/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e91e/11063411/bea7e8c25ea9/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e91e/11063411/6049efe2ff4e/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e91e/11063411/11dbf8883ee3/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e91e/11063411/d19e62d51ac0/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e91e/11063411/dd3f88b6aafb/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e91e/11063411/2e232246739c/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e91e/11063411/2b55f59bd245/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e91e/11063411/eebbcd989e48/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e91e/11063411/0a56a68e4073/gr9.jpg

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