Evidence map›Paper›PMID 42319928›Full record

ArticleScience advances2026

Universal diseased-site targeting via glycolysis-driven lactic acid gradient.

Zheng Cao, Xueqing Cheng, Xiulian Lu, Qian He, Qiong Dai, Liyun Zhang, Xiang Zhang, Jeffrey Harding, Shili Xu, R Michael van Dam and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Zheng CaoDepartment of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0003-1242-3513
Xueqing ChengBeijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China.
Xiulian LuBeijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China.
Qian HeShanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan 030032, China.ORCID 0009-0000-1705-8952
Qiong DaiBeijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China.ORCID 0000-0003-1510-6054
Liyun ZhangShanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan 030032, China.
Xiang ZhangDepartment of Mechanical and Aerospace Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jeffrey HardingDepartment of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine; and UCLA AIDS Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Shili XuDepartment of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA.
R Michael van DamDepartment of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0003-2316-0173
Meiyiming WangBeijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China.ORCID 0009-0007-2774-739X
Yuxi LiBeijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China.ORCID 0000-0002-3490-6703
Pei-Yu ChiouDepartment of Mechanical and Aerospace Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Chaoyong LiuBeijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China.ORCID 0000-0002-0914-687X
Jing WenDepartment of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine; and UCLA AIDS Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0002-6127-6276
Yunfeng LuDepartment of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0002-8589-0297

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Robert Damoiseaux · 1985 to 2026
$134.5M
Improved delivery of bNAbs for targeting CNS infection in infantsR01NS137919 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Jing Wen, Rachael Wolters · 2024 to 2026
$2.5M
NCI NIH HHS P30 CA016042NINDS NIH HHS R01 NS137919
6 · The paper itself

Abstract

Targeted delivery of protein therapeutics remains challenging for translating biologics into effective treatments. Here, we introduce a universal strategy leveraging elevated glycolysis, a hallmark of many pathological states, and its resulting extracellular acidification as a navigational cue. Therapeutic proteins are encapsulated within pH-responsive polymer shells that remain near-neutral at physiological pH but gradually gain positive charge under acidic conditions. This dynamic charge modulation allows nanocapsules to sense pH gradients between healthy and diseased tissues, directing them toward pathological sites. Unlike receptor-mediated targeting that operates over nanometer scales, this receptor-independent approach enables long-range targeting. In vivo models of cancer, chronic inflammation, and acute injury demonstrate selective accumulation of encapsulated proteins at diseased sites, enhancing therapeutic efficacy while reducing systemic toxicity. By transforming a ubiquitous metabolic signature into a directional driving force, this lactate acid gradient-mediated targeting (LaGET) platform offers a previously underexplored paradigm for targeted delivery of protein therapeutics.

Indexed as

Drug Delivery SystemsGlycolysisLactic AcidAnimalsHumansHydrogen-Ion ConcentrationMiceNeoplasmsLactic Acid

Identifiers

PMID42319928
PMCPMC13281810

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.