Evidence map›Paper›PMID 40325025›Full record

ArticleNature communications2025

Rational development of gemcitabine-based nanoplatform for targeting SERPINB9/Granzyme B axis to overcome chemo-immune-resistance.

Haozhe Huang, Yiqing Mu, Yixian Huang, Beihong Ji, Yifei Wang, Chien-Yu Chen, Yuang Chen, Zhangyi Luo, Sihan Li, Ziqian Zhang and 6 more

Abstract read
In one paragraph

Article in Nature communications, 2025. 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.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Clinical application and drug resistance mechanism of gemcitabine.Frontiers in cell and developmental biology · 2025
    Review
  7. Review
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

16 authors.

Haozhe Huang *Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.
Yiqing Mu *Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.
Yixian HuangCenter for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.
Beihong JiDepartment of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.
Yifei WangCenter for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-2832-4125
Chien-Yu ChenCenter for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.
Yuang ChenCenter for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0001-8733-3948
Zhangyi LuoCenter for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.
Sihan LiCenter for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.
Ziqian ZhangCenter for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0001-9294-660X
Luxuan WangDepartment of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.
James F ConwayDepartment of Structural Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-6581-4748
Da YangCenter for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-8336-9457
Junmei WangDepartment of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA. juw79@pitt.edu.ORCID http://orcid.org/0000-0002-9607-8229
Jingjing SunCenter for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA. jsun@unmc.edu.ORCID http://orcid.org/0000-0002-6230-1015
Song LiCenter for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA. sol4@pitt.edu.ORCID http://orcid.org/0000-0003-1658-949X

Funding

Immunostimulatory Nanocarrier for Breast Cancer ImmunochemotherapyR01CA219399 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LI, SONG · 2017 to 2021
$2.3M
Nanoparticles-mediated combination therapy for breast cancerR01CA278608 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Song Li · 2023 to 2026
$2.0M
Combination Therapy for Pancreatic CancerR01CA270623 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Song Li · 2023 to 2026
$1.9M
Nanotherapeutics for Synergistic Targeting of Myc in Prostate CancerR01CA223788 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LI, SONG · 2018 to 2022
$1.8M
New Generation of General AMBER Force Field for Biomedical ResearchR01GM147673 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WANG, JUNMEI, YANG, WEI · 2022 to 2025
$1.5M
Targeting iRhom to Improve Colon Cancer ImmunochemotherapyR01CA295774 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Song Li · 2025 to 2026
$1.1M
Olympus FV3000 Confocal MicroscopeS10OD030254 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GIBBS, ROBERT B · 2022 to 2022
$482k
NCI NIH HHS R01 CA219399NCI NIH HHS R01 CA223788NCI NIH HHS R01 CA270623NCI NIH HHS R01 CA278608NCI NIH HHS R01 CA295774NIGMS NIH HHS R01 GM147673NIH HHS S10 OD030254
6 · The paper itself

Abstract

SERPINB9, an endogenous inhibitor of granzyme B (GzmB), has emerged as a critical factor in the resistance to immunotherapy by protecting cancer cells from GzmB-induced cytotoxicity. However, its role in chemosensitivity remains unknown. In this study, we show that gemcitabine (GEM) treatment upregulates SERPINB9 through transcription factor ATF-3. Interestingly, GEM also induces the expression of GzmB and knockout or knockdown of SERPINB9 results in enhanced response of tumor cells to GEM, suggesting a role of GzmB/SERPINB9 axis in regulating chemosensitivity. To facilitate the therapeutic translation of these findings, we engineer POEM nanocarrier (consisting of lipid-derivatized polylysine (PEG-PLL-Oleic acid, PPO), and GEM-conjugated polylysine (PEG-PLL-OA-GEM, PPOGEM), PPO/PPOGEM (POEM)) that is highly effective in codelivery of built-in GEM and loaded SERPINB9 short interfering RNA (siSPB9). GEM conjugation introduces an additional mechanism of carrier/siRNA interaction in addition to charge-mediated interaction and enables efficient i.v. delivery at lower N/P ratios. Here, we show that co-delivery of GEM and siSPB9 significantly improves antitumor efficacy and remodels the tumor immune microenvironment in pancreatic cancer models, supporting a promising therapeutic strategy.

Indexed as

DeoxycytidineDrug Resistance, NeoplasmGranzymesSerpinsAnimalsAntimetabolites, AntineoplasticCell Line, TumorGemcitabineHumansMiceNanoparticlesPancreatic NeoplasmsRNA, Small InterferingXenograft Model Antitumor AssaysAntimetabolites, AntineoplasticDeoxycytidineGemcitabineGranzymesRNA, Small InterferingSERPINB9 protein, humanSerpins

Identifiers

PMID40325025
PMCPMC12053578

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.