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多功能混合纳米颗粒系统联合近红外激光照射治疗黑色素瘤的概念验证研究

Proof-of-Concept Study of Multifunctional Hybrid Nanoparticle System Combined with NIR Laser Irradiation for the Treatment of Melanoma.

作者信息

Lopes Joana, Ferreira-Gonçalves Tânia, Figueiredo Isabel V, Rodrigues Cecília M P, Ferreira Hugo, Ferreira David, Viana Ana S, Faísca Pedro, Gaspar Maria Manuela, Coelho João M P, Silva Catarina Oliveira, Reis Catarina Pinto

机构信息

Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal.

Pharmacology and Pharmaceutical Care Laboratory, Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.

出版信息

Biomolecules. 2021 Mar 30;11(4):511. doi: 10.3390/biom11040511.

Abstract

The global impact of cancer emphasizes the importance of developing innovative, effective and minimally invasive therapies. In the context of superficial cancers, the development of a multifunctional nanoparticle-based system and its in vitro and in vivo safety and efficacy characterization are, herein, proposed as a proof-of-concept. This multifunctional system consists of gold nanoparticles coated with hyaluronic and oleic acids, and functionalized with epidermal growth factor for greater specificity towards cutaneous melanoma cells. This nanoparticle system is activated by a near-infrared laser. The characterization of this nanoparticle system included several phases, with in vitro assays being firstly performed to assess the safety of gold nanoparticles without laser irradiation. Then, hairless immunocompromised mice were selected for a xenograft model upon inoculation of A375 human melanoma cells. Treatment with near-infrared laser irradiation for five minutes combined with in situ administration of the nanoparticles showed a tumor volume reduction of approximately 80% and, in some cases, led to the formation of several necrotic foci, observed histologically. No significant skin erythema at the irradiation zone was verified, nor other harmful effects on the excised organs. In conclusion, these assays suggest that this system is safe and shows promising results for the treatment of superficial melanoma.

摘要

癌症的全球影响凸显了开发创新、有效且微创治疗方法的重要性。在此,针对浅表性癌症,提出开发一种基于多功能纳米颗粒的系统,并对其进行体外和体内安全性及疗效表征,以此作为概念验证。这种多功能系统由包覆有透明质酸和油酸且用表皮生长因子功能化的金纳米颗粒组成,以增强对皮肤黑色素瘤细胞的特异性。该纳米颗粒系统由近红外激光激活。对该纳米颗粒系统的表征包括几个阶段,首先进行体外试验以评估未进行激光照射时金纳米颗粒的安全性。然后,选择无毛免疫受损小鼠,接种A375人黑色素瘤细胞后建立异种移植模型。近红外激光照射五分钟并原位给予纳米颗粒进行治疗,结果显示肿瘤体积缩小了约80%,在某些情况下,组织学观察到形成了多个坏死灶。未证实照射区域有明显的皮肤红斑,对切除器官也未观察到其他有害影响。总之,这些试验表明该系统是安全的,对浅表性黑色素瘤的治疗显示出有前景的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8344/8103244/39051c477a9c/biomolecules-11-00511-g001.jpg

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