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一种由热敏脂质体和金纳米棒组成的简单纳米平台,通过改进的化疗联合光热疗法治疗骨转移。

A simple nanoplatform of thermo-sensitive liposomes and gold nanorods to treat bone metastasis through improved chemotherapy combined with photothermal therapy.

作者信息

Gu Jia, Jiang Lifan, Chen Zhongping, Qi Jun

机构信息

Department of Burns and Plastic Surgery, Affiliated Hospital of Nantong University, Nantong, People's Republic of China.

Institute of Special Environmental Medicine, Nantong University, Nantong, People's Republic of China.

出版信息

Int J Pharm X. 2024 Aug 30;8:100282. doi: 10.1016/j.ijpx.2024.100282. eCollection 2024 Dec.

Abstract

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.

摘要

骨转移仍然是一个临床挑战,目前仍被认为无法治愈。虽然基于纳米颗粒的药物递送和光热疗法(PTT)在治疗皮下实体瘤方面显示出前景,但由于骨转移部位难以到达以及骨转移的复杂性,它们在治疗骨转移方面的治疗效果有限。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,通过改进的化疗与GNR辅助的PTT相结合来治疗骨转移。首先对TSL的脂质组合进行调整,以调节其在生理条件下的稳定性及其对PTT引起的轻度热疗的敏感性。然后将负载药物的TSL与GNR通过简单孵育结合形成纳米平台。细胞实验表明,在近红外(NIR)照射下,该纳米平台通过PTT、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,有效抑制了肿瘤细胞的活力和迁移能力。在骨转移小鼠模型中,该纳米平台能够将负载的药物和GNR有效递送至骨转移部位,以便在局部NIR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更替,该纳米平台在很大程度上保留了骨结构,从而缓解疼痛并延长生存期。受纳米平台制备和治疗操作简便性的启发,基于脂质体的热敏药物递送与GNR辅助的PTT相结合的策略在治疗骨转移方面被认为极具前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d19/11403519/9c33da27b736/ga1.jpg

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