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一种光活性可注射抗菌水凝胶,通过近红外光介导的肿瘤消融来支持抗原细胞膜和索拉非尼的化学免疫治疗效果。

A photoactive injectable antibacterial hydrogel to support chemo-immunotherapeutic effect of antigenic cell membrane and sorafenib by near-infrared light mediated tumor ablation.

作者信息

Abbaszadeh Samin, Eskandari Mohammad Reza, Nosrati-Siahmazgi Vahideh, Musaie Kiyan, Mehrabi Soraya, Tang Ruikang, Jafari Mohammad Reza, Xiao Bo, Hosseinpour Sarmadi Vahid, Haghi Fakhri, Chen Bo Zhi, Guo Xin Dong, Santos Hélder A, Shahbazi Mohammad-Ali

机构信息

Department of Pharmacology, School of Medicine, Zanjan University of Medical Sciences, 45139-56111, Zanjan, Iran.

Department of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Science, 45139-56184, Zanjan, Iran.

出版信息

Mater Today Bio. 2023 Mar 14;19:100609. doi: 10.1016/j.mtbio.2023.100609. eCollection 2023 Apr.

Abstract

Intravenously administered nanocarriers suffer from off-target distribution, pre-targeting drug leakage, and rapid clearance, limiting their efficiency in tumor eradication. To bypass these challenges, an injectable hydrogel with time- and temperature-dependent viscosity enhancement behavior and self-healing property are reported to assist in the retention of the hydrogel in the tumor site after injection. The cancer cell membrane (CCM) and sorafenib are embedded into the hydrogel to elicit local tumor-specific immune responses and induce cancer cell apoptosis, respectively. In addition, hyaluronic acid (HA) coated BiS nanorods (BiH) are incorporated within the hydrogel to afford prolonged multi-cycle local photothermal therapy (PTT) due to the reduced diffusion of the nanorods to the surrounding tissues as a result of HA affinity toward cancer cells. The results show the promotion of immunostimulatory responses by both CCM and PTT through the release of inflammatory cytokines from immune cells, which allows localized and complete ablation of the breast tumor in an animal model by a single injection of the hydrogel. Moreover, the BiH renders strong antibacterial activity to the hydrogel, which is crucial for the clinical translation of injectable hydrogels as it minimizes the risk of infection in the post-cancer lesion formed by PTT-mediated cancer therapy.

摘要

静脉注射的纳米载体存在靶向分布不佳、预靶向药物泄漏和快速清除等问题,限制了它们根除肿瘤的效率。为了克服这些挑战,据报道一种具有时间和温度依赖性粘度增强行为以及自愈特性的可注射水凝胶有助于在注射后将水凝胶保留在肿瘤部位。癌细胞膜(CCM)和索拉非尼分别嵌入水凝胶中,以引发局部肿瘤特异性免疫反应和诱导癌细胞凋亡。此外,由于透明质酸(HA)对癌细胞的亲和力导致纳米棒向周围组织的扩散减少,因此将HA包被的BiS纳米棒(BiH)掺入水凝胶中以提供延长的多周期局部光热疗法(PTT)。结果表明,CCM和PTT通过免疫细胞释放炎性细胞因子促进免疫刺激反应,通过单次注射水凝胶可在动物模型中实现乳腺肿瘤的局部和完全消融。此外,BiH赋予水凝胶强大的抗菌活性,这对于可注射水凝胶的临床转化至关重要,因为它最大限度地降低了PTT介导的癌症治疗形成的癌症后病变感染的风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8af/10034508/2e5d193e152d/ga1.jpg

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