Evidence map›Paper›PMID 41851499›Full record

ArticleNature nanotechnology2026

Prodrug-tethered lipid nanoparticles for synergistic messenger RNA cancer immunotherapy.

Qiangqiang Shi, Ningqiang Gong, Jinjin Wang, Rohan Palanki, Qiuxian Zheng, Mohamad-Gabriel Alameh, Garima Dwivedi, Benjamin Davis, Jilian Melamed, Zhangyi Luo and 13 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature nanotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

23 authors.

Qiangqiang Shi *Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0009-0009-2503-4374
Ningqiang Gong *Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-9444-8505
Jinjin WangDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8382-044X
Rohan PalankiDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Qiuxian ZhengDepartment of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA.
Mohamad-Gabriel AlamehDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-5672-6930
Garima DwivediDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Benjamin DavisDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jilian MelamedDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Zhangyi LuoDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0009-0007-5791-4013
Junchao XuDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-0725-8111
Christian G Figueroa-EspadaDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-2700-7678
Lulu XueDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-5719-1336
Ye ZengDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-1207-6486
Xuexiang HanDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-0011-5222
Dongyoon KimDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Qinyuan ChenSchool of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Hannah YamagataDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-9525-7102
Hannah C GeislerDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-6455-8183
Rakan El-MaytaDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-5855-233X
Il-Chul YoonDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Drew WeissmanDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-1501-6510
Michael J MitchellDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA. mjmitch@seas.upenn.edu.ORCID http://orcid.org/0000-0002-3628-2244

Funding

A data-driven drug delivery (4D) platform for probing and treating the chemoresistant bone marrow microenvironmentDP2TR002776 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL, MICHAEL J · 2018 to 2018
$2.4M
Engineering Biomaterials to Modulate the Tumor Immune MicroenvironmentK00CA284294 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Christian Gabriel FIGUEROA-ESPADA · 2025 to 2026
$206k
Engineering Biomaterials to Modulate the Bone Marrow Microenvironment in Multiple MyelomaF99CA284294 · NCI · UNIVERSITY OF PENNSYLVANIA · PI FIGUEROA-ESPADA, CHRISTIAN GABRIEL · 2023 to 2024
$98k
NCATS NIH HHS DP2 TR002776NCI NIH HHS F99 CA284294NCI NIH HHS K00 CA284294
6 · The paper itself

Abstract

Regulating T cell phenotypes between activation and exhaustion remains a significant challenge for messenger RNA-based cancer immunotherapy. A potential approach to improve anti-cancer T cell activity is to co-deliver interleukin-12 (IL-12), to stimulate effector T cells, and indoleamine 2,3-dioxygenase (IDO) inhibitor, to suppress T cell exhaustion. Here we design prodrug ionizable lipid nanoparticles (pLNPs), via a library of prodrug ionizable lipids (pILs), incorporating an intracellularly cleavable IDO inhibitor within the pIL structure and encapsulating IL-12 messenger RNA. The lead pIL shows enhanced mRNA transfection over a clinically utilized ionizable lipid, as well as strong immunomodulatory effects via release of the IDO inhibitor. In a subcutaneous colon cancer mouse model, pLNP drives complete regression of primary tumours by eliciting effector T cell infiltration while reducing exhaustion, induces a memory T cell response and stimulates a systemic immune response that allows for regression of distal tumours in this study. These results highlight the promise of pLNPs for small-molecule drug and mRNA combination cancer immunotherapy.

Indexed as

Colonic NeoplasmsImmunotherapyLipidsNanoparticlesProdrugsRNA, MessengerAnimalsCell Line, TumorFemaleHumansIndoleamine-Pyrrole 2,3,-DioxygenaseInterleukin-12LiposomesMiceMice, Inbred C57BLT-LymphocytesIndoleamine-Pyrrole 2,3,-DioxygenaseInterleukin-12Lipid NanoparticlesLipidsLiposomesProdrugsRNA, Messenger

Identifiers

PMID41851499

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.