Self-Assembly Protein Superstructures as a Powerful Chemodynamic Therapy Nanoagent for Glioblastoma Treatment
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ARTICLE
Cite as Nano-Micro Lett. (2020) 12:151 Received: 1 May 2020 Accepted: 18 June 2020 © The Author(s) 2020
https://doi.org/10.1007/s40820-020-00490-6
Self‑Assembly Protein Superstructures as a Powerful Chemodynamic Therapy Nanoagent for Glioblastoma Treatment Tao Zheng1 *, Wentao Wang1, Jon Ashley1, Ming Zhang1 *, Xiaotong Feng1, Jian Shen2,3, Yi Sun1 * * Tao Zheng, [email protected]; Ming Zhang, [email protected]; Yi Sun, [email protected] Department of Health Technology, Technical University of Denmark, 2800 Kongens Lyngby, Denmark 2 Jiangsu Collaborative Innovation Center for Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, People’s Republic of China 3 Key Laboratory of High Performance Polymer Material and Technology of Ministry of Education, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, People’s Republic of China 1
HIGHLIGHTS • A new type of protein nanostructure as a chemodynamic therapy nanoagent was fabricated via proper assembling and crosslinking techniques. • The as-fabricated nanostructures could cross the blood–brain barrier, possessing excellent long circulating times and accumulation properties at the tumor site. • The RBC@Hb@GOx NPs can be regarded as ‘pure particles of drugs,’ which can produce toxic reactive oxygen species to inhibit the growth of orthotopic brain tumor.
ABSTRACT Glioblastoma (GBM) remains a formidable challenge in
oncology. Chemodynamic therapy (CDT) that triggers tumor cell death by reactive oxygen species (ROS) could open up a new door for GBM treatment. Herein, we report a novel CDT nanoagent. Hemoglobin (Hb)
Endothelial cells
RBC@Hb@GOx NPs
Tight junction
Blood-brain barrier
and glucose oxidase (GOx) were employed as powerful CDT catalysts. Instead of encapsulating the proteins in drug delivery nanocarriers, we formulate multimeric superstructures as self-delivery entities by
Apop tosis
crosslinking techniques. Red blood cell (RBC) membranes are camouflaged on the protein superstructures to promote the delivery across blood–brain barrier. The as-prepared RBC@Hb@GOx nanoparticles (NPs) offer superior biocompatibility, simplified structure, and high accumulation at the tumor site. We successfully demonstrated that the
e as le Re
Hb H2O2 GOx
Glucose
Tumor cells
Tumor niche
NPs could efficiently produce toxic ROS to kill U87MG cancer cells in vitro and inhibit the growth of GBM tumor in vivo, suggesting that the new CDT nanoagent holds great promise for treating GBM. KEYWORDS Self-assembly protein superstructures; Glioblastoma therapy; Chemodynamic therapy; Self-delivery entities; Blood– brain barrier
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1 Introduction Glioblastoma multiforme (GBM) is the most malignant cancer in our central nervous system (CNS) [1]. It has an incidence of three per 100,000 adults per year and accounts for 52% of all primary brain tumors. The mainstay of treatment is surgery [2], followed by radiation and chemotherapy [3, 4]. Due to the ag
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