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Biomimetic polymeric nanoparticle-based photodynamic immunotherapy and protection against tumor rechallenge.
Biomaterials Science ( IF 6.6 ) Pub Date : 2020-01-29 , DOI: 10.1039/c9bm01704f Dongyoon Kim 1 , Junho Byun 1 , Jinwon Park 1 , Yeon Lee 1 , Gayong Shim 1 , Yu-Kyoung Oh 1
Biomaterials Science ( IF 6.6 ) Pub Date : 2020-01-29 , DOI: 10.1039/c9bm01704f Dongyoon Kim 1 , Junho Byun 1 , Jinwon Park 1 , Yeon Lee 1 , Gayong Shim 1 , Yu-Kyoung Oh 1
Affiliation
In this study, we sought to design a bionanomaterial that could exert anticancer effects against primary tumors and protect against rechallenged tumors via photodynamic immunotherapy. As a biomaterial, we used an amphiphilic phenylalanine derivative of poly-gamma glutamic acid, which forms nanoparticles by self-assembly. For anticancer effects, we co-entrapped hydrophobic chlorin e6 and monophosphoryl lipid A in the core of the plain amphiphilic phenylalanine nanoparticles (AN), to generate M/C/AN. For comparison, we used plain AN and chlorin e6-loaded AN (C/AN). In vitro studies showed that B16F10 cancer cells treated with C/AN or M/C/AN generated reactive oxygen species and exhibited an enhanced surface display of calreticulin upon exposure to 660 nm light irradiation. C/AN and M/C/AN exerted similar photodynamic anticancer effects; however, M/C/AN, but not C/AN, induced in vitro dendritic cell maturation. Our biodistribution study revealed that C/AN and M/C/AN showed higher accumulation at the tumor tissues compared to that seen in the free chlorin e6-treated group. In B16F10 tumor-bearing mice, the intravenous injection of C/AN or M/C/AN showed similar photodynamic anticancer effects against primary tumors. However, the growth of rechallenged tumors was more significantly inhibited in the M/C/AN group compared to the C/AN group. At day 40 after inoculation of the primary tumor, M/C/AN-treated mice showed 100% survival, whereas the other groups showed 0% survival. In the tumor microenvironment, higher infiltration of CD8+ T cells was observed in the M/C/AN group compared to the other groups. Our results suggest that AN co-loaded with a photosensitizer and an immune stimulant may hold great potential for use in photodynamic immunotherapy to inhibit both primary and metastatic tumors.
中文翻译:
基于仿生聚合物纳米粒子的光动力免疫疗法和针对肿瘤再攻击的保护。
在这项研究中,我们寻求设计一种可以通过光动力免疫疗法对原发肿瘤发挥抗癌作用并保护其免受再发肿瘤侵袭的生物纳米材料。作为生物材料,我们使用了聚γ-谷氨酸的两亲性苯丙氨酸衍生物,该衍生物通过自组装形成纳米颗粒。对于抗癌作用,我们将疏水性二氢卟酚e6和单磷酰基脂质A共同包裹在普通两亲苯基丙氨酸纳米颗粒(AN)的核心中,以生成M / C / AN。为了进行比较,我们使用普通AN和装载二氢二氢卟酚的AN(C / AN)。体外研究表明,用C / AN或M / C / AN处理的B16F10癌细胞在暴露于660 nm光照射下会产生活性氧,并显示钙网蛋白的增强表面显示。C / AN和M / C / AN发挥了类似的光动力抗癌作用。然而,M / C / AN,但不是C / AN,诱导体外树突状细胞成熟。我们的生物分布研究表明,与游离二氢卟酚e6处理组相比,C / AN和M / C / AN在肿瘤组织上显示出更高的积累。在带有B16F10肿瘤的小鼠中,静脉注射C / AN或M / C / AN对原发肿瘤显示出相似的光动力抗癌作用。但是,与C / AN组相比,M / C / AN组中再发肿瘤的生长受到更明显的抑制。接种原发肿瘤后第40天,经M / C / AN处理的小鼠显示100%存活,而其他组显示0%存活。在肿瘤微环境中,与其他组相比,在M / C / AN组中观察到更高的CD8 + T细胞浸润。
更新日期:2020-02-19
中文翻译:
基于仿生聚合物纳米粒子的光动力免疫疗法和针对肿瘤再攻击的保护。
在这项研究中,我们寻求设计一种可以通过光动力免疫疗法对原发肿瘤发挥抗癌作用并保护其免受再发肿瘤侵袭的生物纳米材料。作为生物材料,我们使用了聚γ-谷氨酸的两亲性苯丙氨酸衍生物,该衍生物通过自组装形成纳米颗粒。对于抗癌作用,我们将疏水性二氢卟酚e6和单磷酰基脂质A共同包裹在普通两亲苯基丙氨酸纳米颗粒(AN)的核心中,以生成M / C / AN。为了进行比较,我们使用普通AN和装载二氢二氢卟酚的AN(C / AN)。体外研究表明,用C / AN或M / C / AN处理的B16F10癌细胞在暴露于660 nm光照射下会产生活性氧,并显示钙网蛋白的增强表面显示。C / AN和M / C / AN发挥了类似的光动力抗癌作用。然而,M / C / AN,但不是C / AN,诱导体外树突状细胞成熟。我们的生物分布研究表明,与游离二氢卟酚e6处理组相比,C / AN和M / C / AN在肿瘤组织上显示出更高的积累。在带有B16F10肿瘤的小鼠中,静脉注射C / AN或M / C / AN对原发肿瘤显示出相似的光动力抗癌作用。但是,与C / AN组相比,M / C / AN组中再发肿瘤的生长受到更明显的抑制。接种原发肿瘤后第40天,经M / C / AN处理的小鼠显示100%存活,而其他组显示0%存活。在肿瘤微环境中,与其他组相比,在M / C / AN组中观察到更高的CD8 + T细胞浸润。