2018
DOI: 10.1021/acsnano.8b05265
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Apolipoprotein E Peptide-Directed Chimeric Polymersomes Mediate an Ultrahigh-Efficiency Targeted Protein Therapy for Glioblastoma

Abstract: The inability to cross the blood−brain barrier (BBB) prevents nearly all chemotherapeutics and biotherapeutics from the effective treatment of brain tumors, rendering few improvements in patient survival rates to date. Here, we report that apolipoprotein E peptide [ApoE, (LRKLRKRLL) 2 C] specifically binds to low-density lipoprotein receptor members (LDLRs) and mediates superb BBB crossing and highly efficient glioblastoma (GBM)-targeted protein therapy in vivo. The in vitro BBB model studies reveal that ApoE… Show more

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Cited by 155 publications
(119 citation statements)
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“…Our results suggest that ApoE showed the possibility of use as a BBB shuttle with a higher penetration to the bECs than angiopep-2, although both target the same receptor. [50,54] It interestingly showed good correlation with the results of conventional 2D Transwell assay, [23] which suggested ApoE had better strategy for BBB-crossing though they provide transport ratio only. Thus, our platform is remarkably promising because it can provide comparable results in a quantitative manner between the BBB shuttle candidates.…”
Section: Discussionmentioning
confidence: 89%
See 1 more Smart Citation
“…Our results suggest that ApoE showed the possibility of use as a BBB shuttle with a higher penetration to the bECs than angiopep-2, although both target the same receptor. [50,54] It interestingly showed good correlation with the results of conventional 2D Transwell assay, [23] which suggested ApoE had better strategy for BBB-crossing though they provide transport ratio only. Thus, our platform is remarkably promising because it can provide comparable results in a quantitative manner between the BBB shuttle candidates.…”
Section: Discussionmentioning
confidence: 89%
“…However, although a few studies have attempted to compare various RMT peptides, the lack of a consistent platform has caused difficulty in understanding their performance and specificity to the target receptor. [23,24] An evaluation of BBB-penetrating molecules is conventionally performed in vivo, although their physiology differ from those of humans. [25,26] For example, bovine and porcine model have differences in the sequence of transporters and receptors although they showed high junctional tightness.…”
Section: Introductionmentioning
confidence: 99%
“…As illustrated in Figure 3c, bEnd.3 cells were incubated on the porous membrane, with the trans‐endothelial electrical resistance (TEER) value monitored every 2 days. The BBB model was believed to be successfully established when the TEER value reached 200 Ω cm 2 , comparable to the in vivo BBB . Then, FITC‐labelled TMP NPs were coincubated in an apical chamber with bEnd.3 cells at a concentration of 100 µg mL −1 .…”
Section: Resultsmentioning
confidence: 99%
“…to the cerebrum, thereby compromising the outcomes of diagnosis and therapy . With the increasing development of nanomaterials, receptor‐mediated transcytosis (RMT) has become one of the most promising protocols to overcome the BBB through receptors that are highly expressed on BBB endothelial cells, among which transferrin receptor (TfR) is a promising candidate . Moreover, TfR is also present in substantial quantities on GBM cells due to their high proliferation rate and iron demand .…”
Section: Introductionmentioning
confidence: 99%
“…Peptides are short amino acid sequences that could maintain the same or partial biological functions of natural proteins, and have drawn great interests as promising tools in molecular cell biology or drug candidates in clinical trials [1][2][3][4]. They were reported to play critical roles in cell adhesive and penetrating, tumor targeting, signal transduction, homeostasis and reproduction, cell apoptosis, nuclear localization, and immunity regulation, i.e., induction of T-cell response against pathogens [5][6][7][8][9][10][11][12][13][14][15][16]. Compared with traditional small molecule drugs, peptide-based therapeutics are particularly preferred due to higher specificity towards drug targets, higher safety such as limited adverse effects and immunogenicity, and faster clinical development [17].…”
Section: Introductionmentioning
confidence: 99%