一种简单的热敏脂质体和金纳米棒纳米平台,通过改进化疗结合光热疗法治疗骨转移瘤

IF 5.2 2区 医学 Q1 PHARMACOLOGY & PHARMACY International Journal of Pharmaceutics: X Pub Date : 2024-08-30 DOI:10.1016/j.ijpx.2024.100282
Jia Gu , Lifan Jiang , Zhongping Chen , Jun Qi
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引用次数: 0

摘要

骨转移瘤仍是一项临床难题,目前仍被认为是不治之症。虽然基于纳米颗粒的给药和光热疗法(PTT)在治疗皮下实体瘤方面显示出前景,但由于骨转移部位的不可接近性和骨转移的复杂性,它们在治疗骨转移方面的疗效有限。在此,我们报道了一种由热敏脂质体(TSL)和金纳米棒(GNR)组成的简单纳米平台,通过改进化疗结合 GNR 辅助 PTT 治疗骨转移瘤。首先对 TSL 的脂质组合进行了定制,以调节其在生理条件下的稳定性以及对 PTT 引起的轻度高热反应的敏感性。然后将得到的载药 TSL 与 GNR 结合,通过简单的孵育形成纳米平台。细胞实验表明,在近红外(NIR)照射下,纳米平台通过PTT有效抑制了肿瘤细胞的活力和迁移能力,PTT触发的热敏药物释放,以及PTT增强的肿瘤细胞对药物的敏感性。在小鼠骨转移模型中,该纳米平台能将负载的药物和 GNR 有效地输送到骨转移部位,并在局部近红外照射时快速释放药物。通过杀死肿瘤细胞并重新平衡破骨细胞和成骨细胞的新陈代谢,纳米平台在很大程度上保护了骨结构,从而缓解了疼痛并延长了存活时间。受纳米平台获取和治疗操作简便的启发,基于脂质体的热敏给药策略结合 GNR 辅助 PTT 被认为在治疗骨转移瘤方面大有可为。
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A simple nanoplatform of thermo-sensitive liposomes and gold nanorods to treat bone metastasis through improved chemotherapy combined with photothermal therapy

Bone metastasis remains a clinical challenge and is still considered incurable. While nanoparticles-based drug delivery and photothermal therapy (PTT) show promise in treating subcutaneous solid tumor, their therapeutic outcome in treating bone metastasis is limited, due to the inaccessibility of bone metastatic site and the complexity of bone metastasis. Herein, we reported a simple nanoplatform composed of thermo-sensitive liposomes (TSL) and gold nanorods (GNR) to treat bone metastasis through improved chemotherapy combined with GNR-assisted PTT. Lipid combination of TSL was firstly tailored to regulate its stability under physiological condition as well as its sensitivity in responding to PTT-caused mild hyperthermia. The obtained TSL with loaded drug was then combined with GNR to form the nanoplatform through unsophisticated incubation. Cell experiments revealed that upon near-infrared (NIR) irradiation, the nanoplatform effectively inhibited the viability and migration ability of tumor cells through PTT, PTT-triggered thermo-sensitive drug release, and PTT-augmented sensitivity of tumor cells to drug. In a murine model of bone metastasis, the nanoplatform enabled effective delivery of loaded drug and GNR to bone metastatic site for rapid drug release upon local NIR irradiation. Through killing tumor cells and rebalancing the turnover of osteoclasts and osteoblasts, the nanoplatform largely preserved bone structure for pain relief and survival extension. Inspired by the simplicity of nanoplatform acquirement and treatment operation, the strategy of liposomes-based thermo-sensitive drug delivery in combination with GNR-assisted PTT is considered greatly promising in treating bone metastasis.

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来源期刊
International Journal of Pharmaceutics: X
International Journal of Pharmaceutics: X Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.60
自引率
0.00%
发文量
32
审稿时长
24 days
期刊介绍: International Journal of Pharmaceutics: X offers authors with high-quality research who want to publish in a gold open access journal the opportunity to make their work immediately, permanently, and freely accessible. International Journal of Pharmaceutics: X authors will pay an article publishing charge (APC), have a choice of license options, and retain copyright. Please check the APC here. The journal is indexed in SCOPUS, PUBMED, PMC and DOAJ. The International Journal of Pharmaceutics is the second most cited journal in the "Pharmacy & Pharmacology" category out of 358 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.
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