Exploiting the efficacy of Tyro3 and folate receptors to enhance the delivery of gold nanoparticles into colorectal cancer cells in vitro.
Exploiting the efficacy of Tyro3 and folate receptors to enhance the delivery of gold nanoparticles into colorectal cancer cells in vitro.
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利用Tyro3和叶酸受体的功效来增强金纳米颗粒在体外递送到结直肠癌细胞中。
DOI：
10.1039/d1na00318f
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发表时间：
2021-09-14
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
结直肠癌（CRC）是世界上第四大常见癌症。由于其无症状的性质，CRC在晚期被诊断，其中存活率<5%。此外，使用化学疗法、放射疗法和手术的CRC治疗经常引起不良副作用。因此，金纳米颗粒（GNP）被设想用于诊断和治疗CRC的领域。GNP在纳米尺度上具有独特的物理、化学和电学性质，这使其适合于在生物医学中的应用。然而，为了使GNPs在临床上有效，必须提高其在癌细胞中的内化效率。叶酸受体-α（FR）在CRC细胞中过表达，其中FR有助于细胞内叶酸的摄取。Tyro 3是一种新的酪氨酸激酶受体，驱动细胞增殖，其过表达与CRC的不良预后相关。它们在CRC细胞中相对于正常细胞的上调表达使它们成为使用主动靶向的GNP的理想靶标。因此，在本研究中，使用特异性抗体包被的GNP同时靶向受体FR和Tyro 3，以增强GNP在体外CRC细胞中的摄取和内化。合成四种不同类型的包被的GNP，即GNP-PEG、GNP-抗-FR、GNP-抗-Tyro 3和GNP-抗-（FR + Tyro 3），并与三种CRC细胞系即CRL 1790、CRL 2159和HCT 116孵育（0-50 ng）。发现与单独靶向FR或Tyro 3的GNP相比，GNP-抗（FR + Tyro 3）同时靶向这些受体在CRC细胞中的内化中最有效（p <0.05）。除此之外，结果显示，使用ICP-OES，在CRC细胞中Tyro 3介导与FR相似的内化功效（p <0.05）。与正常细胞相比，FR和Tyro 3受体在CRC细胞中上调。与单独靶向FR或Tyro 3受体的GNP相比，使用GNP同时靶向FR和Tyro 3受体导致CRC细胞中的上级摄取。
Colorectal cancer (CRC) is the fourth most common cancer in the world. Due to its asymptomatic nature, CRC is diagnosed at an advanced stage where the survival rate is <5%. Besides, CRC treatment using chemotherapy, radiotherapy and surgery often causes undesirable side-effects. As such, gold nanoparticles (GNPs) are envisaged in the field for the diagnosis and treatment of CRC. GNPs have unique physical, chemical and electrical properties at the nanoscale which make them suitable for application in biomedicine. However, for GNPs to become clinically effective, their internalisation efficiency in cancer cells must be enhanced. Folate receptor-α (FR) is overexpressed in CRC cells wherein FR helps in the uptake of folic acid within the cells. Tyro3, a novel tyrosine kinase receptor, drives cell proliferation and its overexpression is correlated with poor prognosis in CRC. Their upregulated expression in CRC cells relative to normal cells makes them an ideal target for GNPs using active targeting. Therefore, in this study receptors FR and Tyro3 were simultaneously targeted using specific antibody-coated GNPs in order to enhance the uptake and internalisation of GNPs in CRC cells in vitro. Four different types of coated-GNPs were synthesised GNPs-PEG, GNPs-anti-FR, GNPs-anti-Tyro3 and GNPs-anti-(FR + Tyro3) and incubated (0–50 ng) with three CRC cell lines namely CRL1790, CRL2159 and HCT116. Simultaneous targeting of these receptors by GNPs-anti-(FR + Tyro3) was found to be the most effective in internalisation in CRC cells compared with GNPs targeted singly to FR or Tyro3 (p <0.05). Besides this, results show that Tyro3 mediated similar internalisation efficacy to FR (p <0.05) in CRC cells using ICP-OES. FR and Tyro3 receptors are upregulated in CRC cells compared to normal cells. Simultaneous targeting of FR and Tyro3 receptors using GNPs has resulted in superior uptake in CRC cells compared to GNPs targeting FR or Tyro3 receptors alone.
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影响因子：
--
作者：
Gonzalez-Pons M;Cruz-Correa M
通讯作者：
Cruz-Correa M
影响因子：
3.7
作者：
Holback, Hillary;Yeo, Yoon
通讯作者：
Yeo, Yoon
DOI：
10.1073/pnas.90.15.7044
发表时间：
1993-08-01
影响因子：
11.1
作者：
BIESECKER, LG;GOTTSCHALK, LR;EMERSON, SG
通讯作者：
EMERSON, SG
影响因子：
7.4
作者：
Haiss, Wolfgang;Thanh, Nguyen T. K.;Fernig, David G.
通讯作者：
Fernig, David G.
影响因子：
10
作者：
Chou, Leo Y. T.;Chan, Warren C. W.
通讯作者：
Chan, Warren C. W.