Evidence map›Paper›PMID 42664319›Full record

ArticleScience advances2026

Surface chemistry governs sex-dependent responses to PEG and zwitterionic siRNA nanocarriers in primary macrophages.

Olivia L Lanier, Brinkley A Morse, Ethan P Cisneros, Fabiola A Chapa-Villarreal, Angelea Maestas-Olguin, Reem Al Buzz, Ani Savk, Nicholas A Peppas

Abstract read
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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

8 authors.

Olivia L LanierDepartment of Chemical & Biological Engineering, University of New Mexico, Albuquerque, NM 87131, USA.ORCID 0000-0002-6401-0465
Brinkley A MorseInstitute for Biomaterials, Drug Delivery, and Regenerative Medicine, The University of Texas at Austin, Austin, TX 78712, USA.
Ethan P CisnerosInstitute for Biomaterials, Drug Delivery, and Regenerative Medicine, The University of Texas at Austin, Austin, TX 78712, USA.
Fabiola A Chapa-VillarrealInstitute for Biomaterials, Drug Delivery, and Regenerative Medicine, The University of Texas at Austin, Austin, TX 78712, USA.ORCID 0000-0003-2531-7584
Angelea Maestas-OlguinDepartment of Chemical & Biological Engineering, University of New Mexico, Albuquerque, NM 87131, USA.ORCID 0000-0001-6102-7934
Reem Al BuzzInstitute for Biomaterials, Drug Delivery, and Regenerative Medicine, The University of Texas at Austin, Austin, TX 78712, USA.ORCID 0009-0007-9029-1145
Ani SavkInstitute for Biomaterials, Drug Delivery, and Regenerative Medicine, The University of Texas at Austin, Austin, TX 78712, USA.
Nicholas A PeppasDepartment of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.ORCID 0000-0003-0894-5626

Funding

FAIR Data Competency and Machine Learning Readiness for Biomedical ScientistsK12GM088021 · NIGMS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI REBECCA S. HARTLEY, Diane Lidke · 2009 to 2026
$16.4M
Redefining Nanomedicine Beyond One-Size-Fits-All: Uncovering Mechanisms of Sex Differences and Female Life Stages in Drug DeliveryR35GM160475 · NIGMS · UNIVERSITY OF NEW MEXICO · PI LANIER, OLIVIA LAUREN · 2025 to 2025
$1.8M
Sensor arrays based on molecularly imprinted polymers for diagnosis of Sjogren's syndromeR01EB022025 · NIBIB · UNIVERSITY OF TEXAS AT AUSTIN · PI ANSLYN, ERIC V., PEPPAS, NICHOLAS A · 2016 to 2019
$1.5M
NIBIB NIH HHS R01 EB022025NIGMS NIH HHS K12 GM088021NIGMS NIH HHS R35 GM160475
6 · The paper itself

Abstract

Nanoparticle carriers are widely used for nucleic acid delivery, with poly(ethylene glycol) (PEG)-conjugated nanoparticles emerging as a frontrunner in the field. Growing concerns surrounding PEG immunogenicity have generated interest in zwitterionic polymers as alternative biocompatible surface grafts. At present, there exists a paucity of data regarding zwitterion-conjugated nanoparticle performance in primary immune cells and across biological sexes. Here, we synthesized pH-responsive PEG- and zwitterion-grafted cationic nanoparticles, including PEG methyl ether methacrylate (PEGMMA), carboxybetaine methacrylate (CBMA), sulfobetaine methacrylate (SBMA), and polymeric SBMA, and assessed their cytotoxicity and small interfering RNA (siRNA) delivery in primary male and female murine macrophages. All formulations enabled intracellular siRNA uptake and suppressed tumor necrosis factor-α expression. Sex-dependent effects varied by nanoparticle formulation and biological end point. Zwitterionic nanoparticles exhibited sex-specific effects in cytotoxicity and gene knockdown despite similar uptake, whereas PEGMMA showed higher uptake in females but comparable knockdown across sexes. These findings demonstrate that uptake alone does not predict functional efficacy and highlight the importance of sex-informed evaluation when developing nanomedicines.

Indexed as

Drug CarriersMacrophagesNanoparticlesPolyethylene GlycolsRNA, Small InterferingAnimalsFemaleMaleMiceSurface PropertiesDrug CarriersPolyethylene GlycolsRNA, Small Interfering

Identifiers

PMID42664319
PMCPMC13524025

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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.