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多功能介孔硅纳米系统的可控合成及尺寸效应对精准癌症治疗的影响。

Controlled synthesis and size effects of multifunctional mesoporous silica nanosystem for precise cancer therapy.

机构信息

a Department of Chemistry , Jinan University , Guangzhou , PR China.

出版信息

Drug Deliv. 2018 Nov;25(1):293-306. doi: 10.1080/10717544.2018.1425779.

DOI:10.1080/10717544.2018.1425779
PMID:29334793
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6058695/
Abstract

Nanomaterials-based drug delivery systems display potent applications in cancer therapy, owing to the enhanced permeability and retention effect and diversified chemical modification. In this study, we have tailored and synthesized different sized mesoporous silica nanoparticles (MSNs) through reactant control to investigate the relevancy of nanoparticle size toward anticancer efficacy and suppressing cancer multidrug resistance. The different sized MSNs loaded with anticancer ruthenium complex (RuPOP) and conjugated with folate acid (FA) to enhance the selectivity between cancer and normal cells. The nanosystem (Ru@MSNs) can specifically recognize HepG2 hepatocellular carcinoma cells, thus enhance accumulation and selective cellular uptake. The smaller sized (20 nm) Ru@MSNs exhibit higher anticancer activity against HepG2 cells, while the larger sized (80 nm) Ru@MSNs exhibit higher inhibitory effect against DOX-resistant hepatocellular carcinoma cells (R-HepG2). Moreover, Ru@MSNs induced ROS overproduction in cancer cells, leading to DNA damage and p53 phosphorylation, consequently promoting cancer cells apoptosis. Ru@MSNs (80 nm) also inhibited ABCB1 and ABCG2 expression in R-HepG2 cells to prevent drug efflux, thus overcome multidrug resistance. Ru@MSNs also inhibited tumor growth in vivo without obvious toxicity in major organs of tumor-bearing nude mice. Taken together, these results verify the size effects of MSNs nanosystem for precise cancer therapy.

摘要

基于纳米材料的药物传递系统由于增强的通透性和保留效应以及多样化的化学修饰，在癌症治疗中显示出强大的应用潜力。在本研究中，我们通过反应物控制定制和合成了不同尺寸的介孔硅纳米颗粒（MSNs），以研究纳米颗粒尺寸与抗癌功效和抑制癌症多药耐药性的相关性。不同尺寸的 MSNs 负载抗癌钌配合物（RuPOP）并与叶酸（FA）偶联，以增强癌细胞与正常细胞之间的选择性。纳米系统（Ru@MSNs）可以特异性识别 HepG2 肝癌细胞，从而增强积累和选择性细胞摄取。较小尺寸（20nm）的 Ru@MSNs 对 HepG2 细胞表现出更高的抗癌活性，而较大尺寸（80nm）的 Ru@MSNs 对多柔比星耐药肝癌细胞（R-HepG2）表现出更高的抑制作用。此外，Ru@MSNs 在癌细胞中诱导过量的 ROS 产生，导致 DNA 损伤和 p53 磷酸化，从而促进癌细胞凋亡。Ru@MSNs（80nm）还抑制了 R-HepG2 细胞中 ABCB1 和 ABCG2 的表达，以防止药物外排，从而克服多药耐药性。Ru@MSNs 还抑制了荷瘤裸鼠体内的肿瘤生长，而对主要器官没有明显毒性。总之，这些结果验证了 MSNs 纳米系统在精确癌症治疗中的尺寸效应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5450/6058695/bc22740129a8/IDRD_A_1425779_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5450/6058695/c40679e65185/IDRD_A_1425779_SCH0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5450/6058695/7de962c37a61/IDRD_A_1425779_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5450/6058695/e8bce9f8ee0b/IDRD_A_1425779_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5450/6058695/d08928904689/IDRD_A_1425779_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5450/6058695/1cddc27175dc/IDRD_A_1425779_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5450/6058695/7f6b2b4c752f/IDRD_A_1425779_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5450/6058695/bc22740129a8/IDRD_A_1425779_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5450/6058695/c40679e65185/IDRD_A_1425779_SCH0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5450/6058695/7de962c37a61/IDRD_A_1425779_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5450/6058695/e8bce9f8ee0b/IDRD_A_1425779_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5450/6058695/d08928904689/IDRD_A_1425779_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5450/6058695/1cddc27175dc/IDRD_A_1425779_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5450/6058695/7f6b2b4c752f/IDRD_A_1425779_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5450/6058695/bc22740129a8/IDRD_A_1425779_F0006_C.jpg

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