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<p>In this study, we aimed to develop micro-sized polymer-lipid hybrid hydrogels (HH gels) using alginate-dopamine conjugates (Alg-dp) and extracellular vesicles (EVs) for the concomitant and sustained delivery of chemical anticancer drugs, a transforming growth factor-β receptor 1 kinase inhibitor (SD208) and doxorubicin (Dox), to lung cancer cells. SD208- and Dox-loaded EVs (cEVs) were encapsulated within spherical and micro-sized Alg-dp hydrogels via physical and chemical interactions using a water-in-oil-in-water double emulsion process. The morphologies, diameters, and encapsulation efficiency of the Alg-dp-HH gels were examined. The release profiles of loaded EVs were examined in different concentrations of trypsin and 10% serum conditions. The intracellular uptake of the released fluorescein isothiocyanate-labeled EVs from the Alg-dp HH gels was examined in A549 cells. The extent of apoptosis elicited by cEV-incorporated Alg-dp HH gels was examined using annexin V staining and cell proliferation using the cell counting kit-8 assay. Fabricated EV-loaded Alg-dp HH gels (~ 25&#xa0;μm) exhibited trypsin-responsive release of EVs and sustained release profiles for 7 d in a 10% serum medium. The released EVs were successfully delivered to A549 cells. The cEV-loaded Alg-dp HH gels elicited notable apoptosis and significantly suppressed A549 cell proliferation for 5 d. Thus, cEV-incorporated Alg-dp HH gels delivered SD208 and Dox to lung cancer cells for efficient anticancer effects via concomitant dual-drug delivery in a sustained manner, which could be used in other combination therapies with anticancer drugs.</p>

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Fabrication of hybrid hydrogels for concomitant and sustained delivery of dual anticancer drugs to lung cancer cells

  • 期刊论文

  • 发表日期：

    2026年6月26日

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  • Sehwan Park,
  • Sangho Yeo,
  • Chaewon So,
  • Aejin Lee,
  • Jun Hyuk Lee,
  • Yeonho Bae,
  • Hyejung Mok

摘要

In this study, we aimed to develop micro-sized polymer-lipid hybrid hydrogels (HH gels) using alginate-dopamine conjugates (Alg-dp) and extracellular vesicles (EVs) for the concomitant and sustained delivery of chemical anticancer drugs, a transforming growth factor-β receptor 1 kinase inhibitor (SD208) and doxorubicin (Dox), to lung cancer cells. SD208- and Dox-loaded EVs (cEVs) were encapsulated within spherical and micro-sized Alg-dp hydrogels via physical and chemical interactions using a water-in-oil-in-water double emulsion process. The morphologies, diameters, and encapsulation efficiency of the Alg-dp-HH gels were examined. The release profiles of loaded EVs were examined in different concentrations of trypsin and 10% serum conditions. The intracellular uptake of the released fluorescein isothiocyanate-labeled EVs from the Alg-dp HH gels was examined in A549 cells. The extent of apoptosis elicited by cEV-incorporated Alg-dp HH gels was examined using annexin V staining and cell proliferation using the cell counting kit-8 assay. Fabricated EV-loaded Alg-dp HH gels (~ 25 μm) exhibited trypsin-responsive release of EVs and sustained release profiles for 7 d in a 10% serum medium. The released EVs were successfully delivered to A549 cells. The cEV-loaded Alg-dp HH gels elicited notable apoptosis and significantly suppressed A549 cell proliferation for 5 d. Thus, cEV-incorporated Alg-dp HH gels delivered SD208 and Dox to lung cancer cells for efficient anticancer effects via concomitant dual-drug delivery in a sustained manner, which could be used in other combination therapies with anticancer drugs.