DOPE/DC-胆固醇脂质体和 GCPQ 胶束作为 AZD6244 纳米载体在 3D 结直肠癌细胞体外模型中的功效。

Efficacy of DOPE/DC-cholesterol liposomes and GCPQ micelles as AZD6244 nanocarriers in a 3D colorectal cancer in vitro model.

机构信息

Cancer Nanotechnology Group, University College London, Division of Surgery & Interventional Science, Royal Free Campus, London, NW3 2PF, UK.

Institute of Orthopaedics & Musculoskeletal Sciences, University College London, Division of Surgery & Interventional Science, Stanmore Campus, HA7 4LP, UK.

出版信息

Nanomedicine (Lond). 2016 Feb;11(4):331-44. doi: 10.2217/nnm.15.206. Epub 2016 Jan 20.

DOI:10.2217/nnm.15.206

PMID:26786002

Abstract

AIM

In this work, we use cationic organic nanocarriers as chemotherapy delivery platforms and test them in a colorectal cancer 3D in vitro model.

MATERIALS & METHODS: We used 3beta-(N-[N',N'-dimethylaminoethane]carbamoyl])cholesterol (DC-chol) and dioleoylphosphatidylethanolamine (DOPE) liposomes and N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ) micelles, to deliver AZD6244, a MEK inhibitor, to HCT116 cells cultured as monolayers and in 3D in vitro cancer models (tumoroids).

RESULTS

Nanoparticle-mediated drug delivery was superior to the free drug in monolayer experiments and despite their therapeutic effect being hindered by poor diffusion through the cancer mass, GCPQ micelles were also superior in tumoroids.

CONCLUSION

These results support the role of nanoparticles in improving drug delivery and highlight the need to include 3D cancer models in early phases of drug development.

摘要

目的

在这项工作中，我们使用阳离子有机纳米载体作为化疗药物递送平台，并在结直肠癌细胞 3D 体外模型中进行测试。

材料与方法

我们使用 3β-（N-[N'，N'-二甲氨基乙酰胺]羰基]）胆固醇（DC-chol）和二油酰基磷脂酰乙醇胺（DOPE）脂质体以及 N-棕榈酰-N-单甲基-N，N-二甲基-N，N，N-三甲基-6-O- 聚糖（GCPQ）胶束，将 MEK 抑制剂 AZD6244 递送至单层培养和 3D 体外癌症模型（类器官）中的 HCT116 细胞。