Evidence map›Paper›PMID 39627819›Full record

ArticleJournal of nanobiotechnology2024

A minimalist multifunctional nano-prodrug for drug resistance reverse and integration with PD-L1 mAb for enhanced immunotherapy of hepatocellular carcinoma.

Ting Zou, Yun Huang, Zongtao Zhou, Shuangyan He, Jia Liu, Yalan Chen, Hongdu Liu, Zhonghui Luo, Miaoxin Liu, Hua Wei and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of nanobiotechnology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

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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

11 authors.

Ting Zou *Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science & MOE Key Lab of Rare Pediatric Disease, Hengyang Medical School, University of South China, Hengyang, 421001, China.
Yun Huang *Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science & MOE Key Lab of Rare Pediatric Disease, Hengyang Medical School, University of South China, Hengyang, 421001, China.
Zongtao Zhou *Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science & MOE Key Lab of Rare Pediatric Disease, Hengyang Medical School, University of South China, Hengyang, 421001, China.
Shuangyan He *Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science & MOE Key Lab of Rare Pediatric Disease, Hengyang Medical School, University of South China, Hengyang, 421001, China.
Jia LiuHunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science & MOE Key Lab of Rare Pediatric Disease, Hengyang Medical School, University of South China, Hengyang, 421001, China.
Yalan ChenHunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science & MOE Key Lab of Rare Pediatric Disease, Hengyang Medical School, University of South China, Hengyang, 421001, China.
Hongdu LiuHunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science & MOE Key Lab of Rare Pediatric Disease, Hengyang Medical School, University of South China, Hengyang, 421001, China.
Zhonghui LuoHunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science & MOE Key Lab of Rare Pediatric Disease, Hengyang Medical School, University of South China, Hengyang, 421001, China.
Miaoxin LiuHunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science & MOE Key Lab of Rare Pediatric Disease, Hengyang Medical School, University of South China, Hengyang, 421001, China.
Hua WeiHunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science & MOE Key Lab of Rare Pediatric Disease, Hengyang Medical School, University of South China, Hengyang, 421001, China. weih@usc.edu.cn.
CuiYun YuAffiliated Hospital of Hunan Academy of Chinese Medicine, Hunan Academy of Chinese Medicine, Changsha, 410013, China. yucuiyunusc@hotmail.com.

Funding

National Natural Science Foundtaion of China 82373826
6 · The paper itself

Abstract

Clinical treatment of hepatocellular carcinoma (HCC) with 5-fluorouracil (5-FU), the primary anticancer agent, remains unsatisfactory due to the glutathione (GSH)-associated drug resistance and immunosuppressive microenvironment of HCC. To develop a facile yet robust strategy to overcome 5-FU resistance for enhanced immunotherapy treatment of HCC via all dimensional GSH exhaustion, we report in this study construction of a minimalist prodrug consisting of 5-FU linked to an indoleamine-(2,3)-dioxygenase (IDO) inhibitor (IND) via a disulfide bridge, FU-SS-IND that can further self-assemble into stabilized nanoparticles, FU-SS-IND NPs. Specifically, besides the disulfide linker-induced GSH exhaustion, IND inhibits GSH biosynthesis and enhances the effector function of T cells for turning a "cold" tumor to a "hot" one, which synergistically achieving a tumor inhibition rate (TIR) of 92.5% in a 5-FU resistant mice model. Most importantly, FU-SS-IND NPs could upregulate programmed death ligand 1 (PD-L1) expression on the surface of tumor cells, which enables facile combination with immune checkpoint blockade (ICB) for a ultimate prolonged survival lifetime of 5-FU-resistant tumors-bearing mice. Overall, the minimalist bioreducible nano-prodrug developed herein demonstrates great translatable potential for efficiently reversing drug resistance and enhancing immunotherapy of HCC.

Indexed as

B7-H1 AntigenCarcinoma, HepatocellularDrug Resistance, NeoplasmFluorouracilImmunotherapyLiver NeoplasmsNanoparticlesProdrugsAnimalsAntibodies, MonoclonalCell Line, TumorHumansMiceMice, Inbred BALB CAntibodies, MonoclonalB7-H1 AntigenFluorouracilProdrugs5-FUDrug resistanceGSH exhaustionINDNano-prodrugPD-L1

Identifiers

PMID39627819
PMCPMC11613529

What OpenQuestion holds

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Registered trials

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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.