Faculty Collaboration Database

Molecular mechanism of Gd@C₈₂(OH)₂₂ increasing collagen expression: Implication for encaging tumor. Biomaterials 2018 Jan;152:24-36

Date

10/29/2017

Pubmed ID

29080421

DOI

10.1016/j.biomaterials.2017.10.027

Scopus ID

2-s2.0-85032230328 (requires institutional sign-in at Scopus site)   32 Citations

Abstract

Gadolinium-containing fullerenol Gd@C₈₂(OH)₂₂ has demonstrated low-toxicity and highly therapeutic efficacy in inhibiting tumor growth and metastasis through new strategy of encaging cancer, however, little is known about the mechanisms how this nanoparticle regulates fibroblast cells to prison (instead of poison) cancer cells. Here, we report that Gd@C₈₂(OH)₂₂ promote the binding activity of tumor necrosis factor (TNFα) to tumor necrosis factor receptors 2 (TNFR2), activate TNFR2/p38 MAPK signaling pathway to increase cellular collagen expression in fibrosarcoma cells and human primary lung cancer associated fibroblasts isolated from patients. We also employ molecular dynamics simulations to study the atomic-scale mechanisms that dictate how Gd@C₈₂(OH)₂₂ mediates interactions between TNFα and TNFRs. Our data suggest that Gd@C₈₂(OH)₂₂ might enhance the association between TNFα and TNFR2 through a "bridge-like" mode of interaction; by contrast, the fullerenol appears to inhibit TNFα-TNFR1 association by binding to two of the receptor's cysteine-rich domains. In concert, our results uncover a sequential, systemic process by which Gd@C₈₂(OH)₂₂ acts to prison tumor cells, providing new insights into principles of designs of cancer therapeutics.

Author List

Liu J, Kang SG, Wang P, Wang Y, Lv X, Liu Y, Wang F, Gu Z, Yang Z, Weber JK, Tao N, Qin Z, Miao Q, Chen C, Zhou R, Zhao Y

MESH terms used to index this publication - Major topics in bold

Animals
Antineoplastic Agents
Cell Line, Tumor
Collagen
Fibrosarcoma
Fullerenes
Gadolinium
Humans
Lung Neoplasms
Metal Nanoparticles
Mice
Molecular Dynamics Simulation
Particle Size
Receptors, Tumor Necrosis Factor, Type II
Surface Properties
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha
p38 Mitogen-Activated Protein Kinases