Department of Oncology, Shanghai Fourth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory for the Synthesis and Application of Organic Functional Molecules of Ministry of Education, Key Laboratory for the Green Preparation and Application of Functional Materials of Ministry of Education, College of Chemistry and Chemical Engineering, Hubei University, Wuhan, China.
Drug Deliv. 2022 Dec;29(1):3186-3196. doi: 10.1080/10717544.2022.2128469.
Nanoparticles can promote the accumulation of drugs in tumors. However, they find limited clinical applications because they cannot easily penetrate the stroma of cancer tissues, and it is difficult to control drug release. We developed a multiresponse multistage drug-delivery nanogel with improved tumor permeability and responsiveness to the tumor microenvironment for the controlled delivery of anticancer agents. For this purpose, ∼100 nm multistage drug delivery nanogels with pH, redox, near-infrared stimulation, and enzyme responsiveness were grown in situ using 20 nm gold nanoparticles (AuNPs) via an emulsion-aiding crosslinking technique with cysteine crosslinker. An alginate cysteine AuNP (ACA) nanocarrier can efficiently load the cationic drug doxorubicin (DOX) to produce a multistage drug delivery nanocarrier (DOX@ACA). DOX@ACA can maintain the slow release of DOX and reduce its toxicity. In cancer tissues, the high pH and reductase microenvironment combined with the in vitro delivery of alginate and near-infrared light drove drug release. The developed nanoparticles effectively inhibited cancer cells, and in vivo evaluations showed that they effectively enhanced antitumor activity while having negligible in vivo toxicity to major organs.
纳米颗粒可以促进药物在肿瘤中的积累。然而,由于它们不易穿透癌症组织的基质,并且难以控制药物释放,因此它们在临床上的应用有限。我们开发了一种具有改进的肿瘤通透性和对肿瘤微环境响应性的多响应多阶段药物输送纳米凝胶,用于控制抗癌药物的输送。为此,我们使用胱氨酸交联剂通过乳液辅助交联技术,原位生长了具有 pH、氧化还原、近红外刺激和酶响应性的约 100nm 多阶段药物输送纳米凝胶,使用 20nm 金纳米颗粒 (AuNPs)。海藻酸钠半胱氨酸 AuNP (ACA) 纳米载体可以有效地负载阳离子药物阿霉素 (DOX) 以产生多阶段药物输送纳米载体 (DOX@ACA)。DOX@ACA 可以保持 DOX 的缓慢释放并降低其毒性。在癌症组织中,高 pH 和还原酶微环境结合体外输送的海藻酸钠和近红外光驱动药物释放。所开发的纳米颗粒有效地抑制了癌细胞,体内评估表明,它们有效地增强了抗肿瘤活性,而对主要器官的体内毒性可以忽略不计。
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