---
title: "Ion‑Programmed J‑Aggregates Enable On‑Demand Phototherapy for Diabetic MRSA Wounds"
id: "pubmed-42695131"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42695131"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42695131/"
doi: "10.1002/anie.1142645"
published_at: "2026-10-19T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Ion‑Programmed J‑Aggregates Enable On‑Demand Phototherapy for Diabetic MRSA Wounds
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42695131
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42695131/)
- **DOI:** [10.1002/anie.1142645](https://doi.org/10.1002%2Fanie.1142645)
- **Published At:** 2026-10-19T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Investigators adapted Derjaguin‑Landau‑Verwey‑Overbeek (DLVO) principles to program J‑aggregate formation via long‑range electrostatic interactions; they referenced the Schulze‑Hardy rule relating coagulation to ion valence. - The team modified an anionic pentamethine cyanine (ACy5) by meso‑substitution with charged moieties to direct stacking in different ionic environments. - A probe, **ACy5‑Py‑3Py**, showed sharp J‑aggregation in response to multivalent counterions (z ≥ 2); aggregation was driven by high‑valent ions rather than high dye concentration. - Data indicated **anti‑concentration‑dependent assembly**: ACy5‑Py‑3Py formed stable **J‑aggregates** at concentrations as low as 0.25 µM, overcoming typical reliance on high dye load or nanocarriers. - The study exploited the multivalent‑anion–rich bacterial membrane to trigger **in situ J‑aggregation** on bacterial surfaces, enabling targeted phototheranostic action. - The resulting aggregates had potent phototherapeutic activity against bacteria and allowed theranostic imaging and treatment on demand. - In a diabetic mouse wound model infected with MRSA, ACy5‑Py‑3Py treatment reportedly outperformed vancomycin for wound healing; the authors reported no adverse effects in sterile wounds. - The abstract does not report specific irradiation parameters, precise dosing regimens beyond the noted 0.25 µM aggregation threshold, or full safety pharmacology details; those details are not included in the source abstract.
## Clinical Analysis & Structured Key Points
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Epub 2026 Sep 4. # Ion‑Programmed In Situ J‑Aggregates Overcome Concentration-Dependence for On-Demand Phototherapy of Diabetic Bacterial Infections [Haifeng Ge](https://pubmed.ncbi.nlm.nih.gov/?term=Ge+H&cauthor_id=42695131)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42695131/#full-view-affiliation-1 "Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research \(Ministry of Education\), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, P. R. China."), [Chenxi Lu](https://pubmed.ncbi.nlm.nih.gov/?term=Lu+C&cauthor_id=42695131)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42695131/#full-view-affiliation-1 "Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research \(Ministry of Education\), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, P. R. China."), [Li Xu](https://pubmed.ncbi.nlm.nih.gov/?term=Xu+L&cauthor_id=42695131)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42695131/#full-view-affiliation-2 "Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China."), [Suanquan He](https://pubmed.ncbi.nlm.nih.gov/?term=He+S&cauthor_id=42695131)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42695131/#full-view-affiliation-1 "Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research \(Ministry of Education\), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, P. R. China."), [Zhipengjun Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+Z&cauthor_id=42695131)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42695131/#full-view-affiliation-1 "Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research \(Ministry of Education\), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, P. R. China."), [Zhe Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+Z&cauthor_id=42695131)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42695131/#full-view-affiliation-2 "Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China."), [Hongwen Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+H&cauthor_id=42695131)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42695131/#full-view-affiliation-1 "Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research \(Ministry of Education\), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, P. R. China.") Affiliations Expand ### Affiliations * 1 Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, P. R. China. * 2 Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China. * PMID: **42695131** * DOI: [ 10.1002/anie.1142645 ](https://doi.org/10.1002/anie.1142645) Item in Clipboard # Ion‑Programmed In Situ J‑Aggregates Overcome Concentration-Dependence for On-Demand Phototherapy of Diabetic Bacterial Infections Haifeng Ge et al. Angew Chem Int Ed Engl. 2026. Show details Display options Display options Format Abstract PubMed PMID Angew Chem Int Ed Engl Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Angew+Chem+Int+Ed+Engl%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Angew+Chem+Int+Ed+Engl%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42695131/) . 2026 Oct 19;65(43):e1142645. doi: 10.1002/anie.1142645. Epub 2026 Sep 4. ### Authors [Haifeng Ge](https://pubmed.ncbi.nlm.nih.gov/?term=Ge+H&cauthor_id=42695131)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42695131/#short-view-affiliation-1 "Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research \(Ministry of Education\), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, P. R. China."), [Chenxi Lu](https://pubmed.ncbi.nlm.nih.gov/?term=Lu+C&cauthor_id=42695131)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42695131/#short-view-affiliation-1 "Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research \(Ministry of Education\), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, P. R. China."), [Li Xu](https://pubmed.ncbi.nlm.nih.gov/?term=Xu+L&cauthor_id=42695131)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42695131/#short-view-affiliation-2 "Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China."), [Suanquan He](https://pubmed.ncbi.nlm.nih.gov/?term=He+S&cauthor_id=42695131)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42695131/#short-view-affiliation-1 "Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research \(Ministry of Education\), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, P. R. China."), [Zhipengjun Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+Z&cauthor_id=42695131)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42695131/#short-view-affiliation-1 "Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research \(Ministry of Education\), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, P. R. China."), [Zhe Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+Z&cauthor_id=42695131)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42695131/#short-view-affiliation-2 "Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China."), [Hongwen Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+H&cauthor_id=42695131)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42695131/#short-view-affiliation-1 "Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research \(Ministry of Education\), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, P. R. China.") ### Affiliations * 1 Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, P. R. China. * 2 Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China. * PMID: **42695131** * DOI: [ 10.1002/anie.1142645 ](https://doi.org/10.1002/anie.1142645) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID Linked Discoveries ## Abstract J-aggregates are attractive for phototheranostics due to their enhanced absorption, redshift, and photostability, but they typically require high dye concentrations or nanocarriers. Inspired by Derjaguin-Landau-Verwey-Overbeek (DLVO) theory, in which multivalent ions promote colloid coagulation by compressing the electrical double layer and reducing electrostatic repulsion (Schulze-Hardy rule: CCC ∝ 1/z6), we developed a strategy based on long-range electrostatic interactions to construct high‑valent‑ion-programmable J-aggregates. By meso‑substituting positive or negative charged moieties to an anionic pentamethine cyanine (ACy5) to manipulate its stacking preference in ionic environment, we obtained probes capable of undergoing sharp J‑aggregation in response to high‑valent counterions (z ≥ 2). Benefiting from the long‑range nature of electrostatic interactions, ACy5-Py-3Py exhibited anti-concentration‑dependent assembly and formed stable J‑aggregates even at concentrations as low as 0.25 µM. Taking advantage of the multivalent-anion-rich bacterial membrane, we used ACy5-Py-3Py to achieve in situ J-aggregation on bacterial surfaces. The resulting aggregates exhibit potent phototherapeutic activity, enabling efficient bacterial theranostics and outperforming vancomycin in healing MRSA-infected wounds in diabetic mice. No adverse effects were observed in sterile wounds, confirming high biocompatibility. Together with its specific bactericidal efficacy, ACy5‑Py‑3Py represents a promising on‑demand phototheranostic J‑aggregate agent. **Keywords:** DLVO; NIR J‐aggregates; NIR‑phototherapeutics; anionic pentamethine cyanine; bacterial infections. © 2026 Wiley‐VCH GmbH. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Similar articles * [ Interaction forces, heteroaggregation, and deposition involving charged colloidal particles. ](https://pubmed.ncbi.nlm.nih.gov/24849534/) Trefalt G, Ruiz-Cabello FJ, Borkovec M.Trefalt G, et al.J Phys Chem B. 2014 Jun 12;118(23):6346-55. doi: 10.1021/jp503564p. Epub 2014 Jun 2.J Phys Chem B. 2014.PMID: 24849534 * [ Destabilization of colloidal suspensions by multivalent ions and polyelectrolytes: from screening to overcharging. ](https://pubmed.ncbi.nlm.nih.gov/22468583/) Szilagyi I, Sadeghpour A, Borkovec M.Szilagyi I, et al.Langmuir. 2012 Apr 17;28(15):6211-5. doi: 10.1021/la300542y. Epub 2012 Apr 5.Langmuir. 2012.PMID: 22468583 * [ In situ orderly self-assembly strategy affording NIR-II-J-aggregates for in vivo imaging and surgical navigation. ](https://pubmed.ncbi.nlm.nih.gov/37012267/) Li Z, Liang PZ, Xu L, Zhang XX, Li K, Wu Q, Lou XF, Ren TB, Yuan L, Zhang XB.Li Z, et al.Nat Commun. 2023 Apr 3;14(1):1843. doi: 10.1038/s41467-023-37586-7.Nat Commun. 2023.PMID: 37012267Free PMC article. * [ The polarization model for hydration/double layer interactions: the role of the electrolyte ions. ](https://pubmed.ncbi.nlm.nih.gov/15581557/) Manciu M, Ruckenstein E.Manciu M, et al.Adv Colloid Interface Sci. 2004 Dec 31;112(1-3):109-28. doi: 10.1016/j.cis.2004.09.001.Adv Colloid Interface Sci. 2004.PMID: 15581557Review. * [ Forces between solid surfaces in aqueous electrolyte solutions. ](https://pubmed.ncbi.nlm.nih.gov/31837508/) Smith AM, Borkovec M, Trefalt G.Smith AM, et al.Adv Colloid Interface Sci. 2020 Jan;275:102078. doi: 10.1016/j.cis.2019.102078. Epub 2019 Nov 22.Adv Colloid Interface Sci. 2020.PMID: 31837508Review. [ See all similar articles ](https://pubmed.ncbi.nlm.nih.gov/?linkname=pubmed_pubmed&from_uid=42695131) ## References 1. 1. E. E. Jelley, “Spectral Absorption and Fluorescence of Dyes in the Molecular State,” Nature 138 (1936): 1009–1010, . 2. 1. F. Würthner, T. E. Kaiser, and C. R. Saha‐Möller, “J‐Aggregates: From Serendipitous Discovery to Supramolecular Engineering of Functional Dye Materials,” Angewandte Chemie, International Edition 50 (2011): 3376–3410, . 3. 1. Z. Chen, Y. Liu, W. Wagner, et al., “Near‐IR Absorbing J‐Aggregate of an Amphiphilic BF2‐Azadipyrromethene Dye by Kinetic Cooperative Self‐Assembly,” Angewandte Chemie, International Edition 56 (2017): 5729–5733, . 4. 1. Y. Liu, G. Liu, W. Zhou, et al., “In Situ Self‐Assembled J‐Aggregate Nanofibers of Glycosylated Aza‐BODIPY for Synergetic Cell Membrane Disruption and Type I Photodynamic Therapy,” Angewandte Chemie, International Edition 62 (2023): e202309786, . 5. 1. T. Kim, B. Hwang, B. Lee, J. Bae, and Y. Kim, “Selective Monitoring and Imaging of Eosinophil Peroxidase Activity With a J‐Aggregating Probe,” Journal of the American Chemical Society 140 (2018): 11771–11776, . 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