Evidence map›Paper›PMID 34069106›Full record

ArticleCancers2021

Transferrin Modified GSH Sensitive Hyaluronic Acid Derivative Micelle to Deliver HSP90 Inhibitors to Enhance the Therapeutic Efficacy of Brain Cancers.

Tilahun Ayane Debele, Ping-Ching Wu, Yu-Feng Wei, Jian-Ying Chuang, Kwang-Yu Chang, Jui-Hung Tsai, Wen-Pin Su

Abstract read
In one paragraph

Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Review
  2. Article
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  5. Review
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Tilahun Ayane DebeleInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, No. 35, Tainan 704, Taiwan.ORCID 0000-0002-1039-9620
Ping-Ching WuDepartment of Biomedical Engineering, National Cheng Kung University, Tainan 701, Taiwan.
Yu-Feng WeiDepartment of Internal Medicine, School of Medicine for International Students, College of Medicine, E-Da Cancer Hospital, I-Shou University, Kaohsiung 824, Taiwan.ORCID 0000-0002-6380-3527
Jian-Ying ChuangThe Ph.D. Program for Neural Regenerative Medicine, Taipei Medical University, Taipei 115, Taiwan.ORCID 0000-0001-5124-0643
Kwang-Yu ChangNational Institute of Cancer Research, National Health Research Institute, Tainan 704, Taiwan.
Jui-Hung TsaiDepartments of Oncology and Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
Wen-Pin SuInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, No. 35, Tainan 704, Taiwan.ORCID 0000-0003-0863-203X

Funding

Ministry of Science and Technology, Taiwan 108-2811-B-006-501; 108-2811-B-006-525; 106-2314-B-006-074-MY3; 109-2314-B-006-078 and 109-2314-B-006-084-MY3National Cheng Kung University Hospital 10703056 and 10804005
6 · The paper itself

Abstract

Herein, GSH-sensitive hyaluronic acid-poly(lactic-co-glycolic acid) (HA-SS-PLGA) was synthesized. Surface modification of PLGA with hyaluronic acid produced a highly stable micelle at physiological pH while a micelle was destabilized at a higher GSH level. Fluorescence microscopy results showed that rhodamine-encapsulated micelle was taken up by brain cancer cells, while competitive inhibition was observed in the presence of free HA and free transferrin. In vitro cytotoxicity results revealed that transferrin-targeted nanoformulated AUY922 (TF-NP-AUY922) shows higher cytotoxicity than either free AUY922 or non-targeted AUY922-loaded micelles (NP-AUY922). In comparison to the control groups, free AUY922, TF-NP-AUY922 or NP-AUY922 treatment revealed the upregulation of HSP70, while the expression of HSP90 client proteins was simultaneously depleted. In addition, the treatment group induced caspase-dependent PARP cleavage and the upregulation of p53 expression, which plays a key role in apoptosis of brain cancer cells. In vivo and ex vivo biodistribution studies showed that cypate-loaded micelle was taken up and accumulated in the tumor regions. Furthermore, in vivo therapeutic efficacy studies revealed that the AUY922-loaded micelle significantly suppressed tumor growth in comparison to the free AUY922, or control groups using tumor-bearing NOD-SCID mice. Moreover, biochemical index and histological analysis revealed synthesized micelle does not show any significant cytotoxicity to the selected major organs. Overall, a synthesized micelle is the best carrier for AUY922 to enhance the therapeutic efficiency of brain cancer.

Indexed as

brain cancerGSH-sensitive micellehyaluronic acidpoly(lactic-co-glycolic) acid

Identifiers

PMID34069106
PMCPMC8156315

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.