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Enhancing Human Skin Penetration with Biodegradable Enzymatic Nanomotors.

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Title: Enhancing Human Skin Penetration with Biodegradable Enzymatic Nanomotors.
Authors: Prado-Morales C; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST) , 08028Barcelona, Spain.; Universitat de Barcelona, Doctorate in Biotechnology, Facultat de Farmàcia i Ciències de l'Alimentació, 08028Barcelona, Spain., Waaijman T; Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Location VUMC, 1081 HVAmsterdam, The Netherlands., Macías-Tarrío I; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST) , 08028Barcelona, Spain.; Universitat de Barcelona, Doctorate in Biotechnology, Facultat de Farmàcia i Ciències de l'Alimentació, 08028Barcelona, Spain.; Departament de Bioquímica i Fisologia, Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona, 08028Barcelona, Spain., Huck-Iriart C; ALBA Synchrotron Light Source, Cerdanyola del Vallès, 08290Barcelona, Spain., Russo T; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST) , 08028Barcelona, Spain.; Universitat de Barcelona, Facultat de Biologia, 08028Barcelona, Spain., Gálvez-Savoca J; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST) , 08028Barcelona, Spain., Rodriguez-Emmenegger C; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST) , 08028Barcelona, Spain.; DWI - Leibniz Institute for Interactive Materials, 52074Aachen, Germany.; Institució Catalana de Recerca i Estudis Avaņats (ICREA), 08010Barcelona, Spain., Koning JJ; Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Location VUMC, 1081 HVAmsterdam, The Netherlands.; Amsterdam institute for Immunology and Infectious diseases, Inflammatory diseases, 1081 HVAmsterdam, The Netherlands., Sánchez S; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST) , 08028Barcelona, Spain.; Institució Catalana de Recerca i Estudis Avaņats (ICREA), 08010Barcelona, Spain.
Source: ACS nano [ACS Nano] 2026 Aug 18; Vol. 20 (32), pp. 23013-23033.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: American Chemical Society Country of Publication: United States NLM ID: 101313589 Publication Model: Print Cited Medium: Internet ISSN: 1936-086X (Electronic) Linking ISSN: 19360851 NLM ISO Abbreviation: ACS Nano Subsets: MEDLINE
Imprint Name(s): Original Publication: Washington D.C. : American Chemical Society
MeSH Terms: Skin*/metabolism , Urease*/metabolism , Urease*/chemistry , Skin Absorption*, Polylactic Acid-Polyglycolic Acid Copolymer/chemistry ; Lactic Acid/chemistry ; Lactic Acid/metabolism ; Polyglycolic Acid/chemistry ; Polyglycolic Acid/metabolism ; Humans ; Administration, Cutaneous
Abstract: The skin is the body's primary biological barrier, largely due to the highly organized structure of the stratum corneum (SC). Although essential for protection, this barrier function limits the efficacy of transdermal drug delivery, as most topically applied compounds fail to reach deeper skin layers at therapeutically relevant concentrations. Existing approaches often rely on physical disruption of the barrier, which can cause undesirable side effects. Moreover, many prior studies have been conducted in murine models, which do not accurately recapitulate human skin physiology, hindering the translation to humans. Here, we present an alternative approach using enzymatically powered nanomotors tested in a human reconstructed skin model. We developed organic nanomotors composed of poly(lactic-co-glycolic acid) functionalized with urease, and we proved their biocompatibility and degradability. Our results show that nanomotors penetrate the skin with 15.7% efficacy, 2.5 times more than passive nanoparticle controls. This enhanced penetration is attributed to their active motion and their ability to induce alterations in the lipid organization of the SC, an effect confirmed by synchrotron radiation small-angle X-ray scattering and electron microscopy. These findings highlight the potential of enzymatic nanomotors as a nondisruptive and effective platform for future transdermal delivery in human skin, combining advantages of both chemical enhancers and nanoparticles.
(© 2026 The Authors. Published by American Chemical Society.)
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Grant Information: CEX2023-001282 S Ministerio de Ciencia, Innovaci?n y Universidades; PID2021-128417OB-I00 Ministerio de Ciencia, Innovaci?n y Universidades; PRE2022-102542 Ministerio de Ciencia, Innovaci?n y Universidades; NA Generalitat de Catalunya; 2021 SGR 01606 Departament d'Innovaci?, Universitats i Empresa, Generalitat de Catalunya; 1292.19.019 Nederlandse Organisatie voor Wetenschappelijk Onderzoek; NA European Social Fund Plus; NA European Regional Development Fund; 101189426 Horizon 2020 European Commission (EC); 2024098683 ALBA Synchrotron; 20250370417 ALBA Synchrotron; 866348 Horizon 2020 European Commission (EC)
Contributed Indexing: Keywords: biological barrier; human skin model; nanobots; nanomedicine; nanomotors; skin; transdermal delivery
Substance Nomenclature: 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
EC 3.5.1.5 (Urease)
33X04XA5AT (Lactic Acid)
26009-03-0 (Polyglycolic Acid)
Entry Date(s): Date Created: 20260818 Date Completed: 20260818 Latest Revision: 20260822
Update Code: 20260822
PubMed Central ID: PMC13492477
DOI: 10.1021/acsnano.6c11619
PMID: 42611229
Database: MEDLINE
FullText Text:
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Header DbId: cmedm
DbLabel: MEDLINE
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AccessLevel: 3
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
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Items – Name: Title
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  Group: Ti
  Data: Enhancing Human Skin Penetration with Biodegradable Enzymatic Nanomotors.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AU" term="%22Prado-Morales+C%22">Prado-Morales C</searchLink>; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST) , 08028Barcelona, Spain.; Universitat de Barcelona, Doctorate in Biotechnology, Facultat de Farmàcia i Ciències de l'Alimentació, 08028Barcelona, Spain.<br /><searchLink fieldCode="AU" term="%22Waaijman+T%22">Waaijman T</searchLink>; Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Location VUMC, 1081 HVAmsterdam, The Netherlands.<br /><searchLink fieldCode="AU" term="%22Macías-Tarrío+I%22">Macías-Tarrío I</searchLink>; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST) , 08028Barcelona, Spain.; Universitat de Barcelona, Doctorate in Biotechnology, Facultat de Farmàcia i Ciències de l'Alimentació, 08028Barcelona, Spain.; Departament de Bioquímica i Fisologia, Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona, 08028Barcelona, Spain.<br /><searchLink fieldCode="AU" term="%22Huck-Iriart+C%22">Huck-Iriart C</searchLink>; ALBA Synchrotron Light Source, Cerdanyola del Vallès, 08290Barcelona, Spain.<br /><searchLink fieldCode="AU" term="%22Russo+T%22">Russo T</searchLink>; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST) , 08028Barcelona, Spain.; Universitat de Barcelona, Facultat de Biologia, 08028Barcelona, Spain.<br /><searchLink fieldCode="AU" term="%22Gálvez-Savoca+J%22">Gálvez-Savoca J</searchLink>; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST) , 08028Barcelona, Spain.<br /><searchLink fieldCode="AU" term="%22Rodriguez-Emmenegger+C%22">Rodriguez-Emmenegger C</searchLink>; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST) , 08028Barcelona, Spain.; DWI - Leibniz Institute for Interactive Materials, 52074Aachen, Germany.; Institució Catalana de Recerca i Estudis Avaņats (ICREA), 08010Barcelona, Spain.<br /><searchLink fieldCode="AU" term="%22Koning+JJ%22">Koning JJ</searchLink>; Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Location VUMC, 1081 HVAmsterdam, The Netherlands.; Amsterdam institute for Immunology and Infectious diseases, Inflammatory diseases, 1081 HVAmsterdam, The Netherlands.<br /><searchLink fieldCode="AU" term="%22Sánchez+S%22">Sánchez S</searchLink>; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST) , 08028Barcelona, Spain.; Institució Catalana de Recerca i Estudis Avaņats (ICREA), 08010Barcelona, Spain.
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  Data: <searchLink fieldCode="JN" term="%22101313589%22">ACS nano</searchLink> [ACS Nano] 2026 Aug 18; Vol. 20 (32), pp. 23013-23033.
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  Data: English
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  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22American+Chemical+Society%22">American Chemical Society </searchLink><i>Country of Publication: </i>United States <i>NLM ID: </i>101313589 <i>Publication Model: </i>Print <i>Cited Medium: </i>Internet <i>ISSN: </i>1936-086X (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2219360851%22">19360851 </searchLink><i>NLM ISO Abbreviation: </i>ACS Nano <i>Subsets: </i>MEDLINE
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  Data: <i>Original Publication</i>: Washington D.C. : American Chemical Society
– Name: SubjectMESH
  Label: MeSH Terms
  Group: Su
  Data: <searchLink fieldCode="MM" term="%22Skin%22">Skin*</searchLink>/<searchLink fieldCode="MM" term="%22Skin+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Urease%22">Urease*</searchLink>/<searchLink fieldCode="MM" term="%22Urease+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Urease%22">Urease*</searchLink>/<searchLink fieldCode="MM" term="%22Urease+chemistry%22">chemistry</searchLink> <br /><searchLink fieldCode="MM" term="%22Skin+Absorption%22">Skin Absorption*</searchLink><br /><searchLink fieldCode="MH" term="%22Polylactic+Acid-Polyglycolic+Acid+Copolymer%22">Polylactic Acid-Polyglycolic Acid Copolymer</searchLink>/<searchLink fieldCode="MH" term="%22Polylactic+Acid-Polyglycolic+Acid+Copolymer+chemistry%22">chemistry</searchLink> ; <searchLink fieldCode="MH" term="%22Lactic+Acid%22">Lactic Acid</searchLink>/<searchLink fieldCode="MH" term="%22Lactic+Acid+chemistry%22">chemistry</searchLink> ; <searchLink fieldCode="MH" term="%22Lactic+Acid%22">Lactic Acid</searchLink>/<searchLink fieldCode="MH" term="%22Lactic+Acid+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Polyglycolic+Acid%22">Polyglycolic Acid</searchLink>/<searchLink fieldCode="MH" term="%22Polyglycolic+Acid+chemistry%22">chemistry</searchLink> ; <searchLink fieldCode="MH" term="%22Polyglycolic+Acid%22">Polyglycolic Acid</searchLink>/<searchLink fieldCode="MH" term="%22Polyglycolic+Acid+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Administration%2C+Cutaneous%22">Administration, Cutaneous</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: The skin is the body's primary biological barrier, largely due to the highly organized structure of the stratum corneum (SC). Although essential for protection, this barrier function limits the efficacy of transdermal drug delivery, as most topically applied compounds fail to reach deeper skin layers at therapeutically relevant concentrations. Existing approaches often rely on physical disruption of the barrier, which can cause undesirable side effects. Moreover, many prior studies have been conducted in murine models, which do not accurately recapitulate human skin physiology, hindering the translation to humans. Here, we present an alternative approach using enzymatically powered nanomotors tested in a human reconstructed skin model. We developed organic nanomotors composed of poly(lactic-co-glycolic acid) functionalized with urease, and we proved their biocompatibility and degradability. Our results show that nanomotors penetrate the skin with 15.7% efficacy, 2.5 times more than passive nanoparticle controls. This enhanced penetration is attributed to their active motion and their ability to induce alterations in the lipid organization of the SC, an effect confirmed by synchrotron radiation small-angle X-ray scattering and electron microscopy. These findings highlight the potential of enzymatic nanomotors as a nondisruptive and effective platform for future transdermal delivery in human skin, combining advantages of both chemical enhancers and nanoparticles.<br /> (© 2026 The Authors. Published by American Chemical Society.)
– Name: Ref
  Label: References
  Group: RefInfo
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– Name: GrantInfo
  Label: Grant Information
  Group: Grant
  Data: CEX2023-001282 S Ministerio de Ciencia, Innovaci?n y Universidades; PID2021-128417OB-I00 Ministerio de Ciencia, Innovaci?n y Universidades; PRE2022-102542 Ministerio de Ciencia, Innovaci?n y Universidades; NA Generalitat de Catalunya; 2021 SGR 01606 Departament d'Innovaci?, Universitats i Empresa, Generalitat de Catalunya; 1292.19.019 Nederlandse Organisatie voor Wetenschappelijk Onderzoek; NA European Social Fund Plus; NA European Regional Development Fund; 101189426 Horizon 2020 European Commission (EC); 2024098683 ALBA Synchrotron; 20250370417 ALBA Synchrotron; 866348 Horizon 2020 European Commission (EC)
– Name: SubjectMinor
  Label: Contributed Indexing
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  Data: <i>Keywords: </i>biological barrier; human skin model; nanobots; nanomedicine; nanomotors; skin; transdermal delivery
– Name: NumberCAS
  Label: Substance Nomenclature
  Group: ID
  Data: 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)<br />EC 3.5.1.5 (Urease)<br />33X04XA5AT (Lactic Acid)<br />26009-03-0 (Polyglycolic Acid)
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  Data: <i>Date Created: </i>20260818 <i>Date Completed: </i>20260818 <i>Latest Revision: </i>20260822
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  Data: 20260822
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  Data: PMC13492477
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  Data: 10.1021/acsnano.6c11619
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  Data: 42611229
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42611229
RecordInfo BibRecord:
  BibEntity:
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      – Type: doi
        Value: 10.1021/acsnano.6c11619
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: 23013
    Subjects:
      – SubjectFull: Polylactic Acid-Polyglycolic Acid Copolymer chemistry
        Type: general
      – SubjectFull: Lactic Acid chemistry
        Type: general
      – SubjectFull: Lactic Acid metabolism
        Type: general
      – SubjectFull: Polyglycolic Acid chemistry
        Type: general
      – SubjectFull: Polyglycolic Acid metabolism
        Type: general
      – SubjectFull: Humans
        Type: general
      – SubjectFull: Administration, Cutaneous
        Type: general
      – SubjectFull: Skin metabolism
        Type: general
      – SubjectFull: Urease metabolism
        Type: general
      – SubjectFull: Urease chemistry
        Type: general
      – SubjectFull: Skin Absorption
        Type: general
    Titles:
      – TitleFull: Enhancing Human Skin Penetration with Biodegradable Enzymatic Nanomotors.
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            – D: 18
              M: 08
              Text: 2026 Aug 18
              Type: published
              Y: 2026
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              Value: 1936-086X
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