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Peer-reviewedCC BY 4.0Molecules

Agarose-Encapsulated Multifunctional Microspheres with High Drug Payload and Multimodal Imaging Capability for Arterial Embolization–Associated Hyperthermia Therapy

  1. 1School of Automation, Hangzhou Dianzi University, Hangzhou 310018, China
  2. 2Department of Interventional Vascular Surgery, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou 325200, China
  3. 3Department of Clinical Laboratory, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou 325200, China

Abstract

Hepatocellular carcinoma (HCC) represents a leading cause of cancer-related mortality worldwide, and transarterial chemoembolization (TACE) remains the standard first-line locoregional therapy for intermediate-stage HCC. Nevertheless, conventional TACE frequently yields suboptimal therapeutic efficacy in advanced or heterogeneous tumors, necessitating combined therapeutic strategies. Herein, we report a one-step emulsion fabrication strategy to develop agarose-encapsulated multifunctional microspheres (AEMMs) using low-cost, biocompatible agarose as the scaffold matrix. AEMMs co-encapsulate PSS for electrostatic drug binding, iodixanol as a dual-contrast agent for CT and DSA, and superparamagnetic Fe3O4 nanoparticles that serve as both MRI contrast agent and NIR photothermal converter. In vitro evaluation demonstrates that AEMMs achieve ultrahigh drug loading capacities of 89.87 ± 1.78 mg/mL for DOX or 90.60 ± 0.84 mg/mL for Irinotecan, which are comparable to commercial CalliSpheres® and nearly twofold higher than DC Beads®. Photothermal evaluation confirms that AEMMs induce rapid temperature elevation above 50 °C within 3 min under 808 nm laser irradiation, with excellent thermal stability and reproducibility over repeated on–off cycles. Furthermore, AEMMs provide excellent complementary contrast for CT, DSA, and T2-weighted MRI, enabling real-time embolization monitoring and postoperative assessment. Blank AEMMs exhibit negligible cytotoxicity against HepG2 cells even at high concentrations, verifying favorable biocompatibility. Collectively, AEMMs integrate mechanical embolization, localized sustained chemotherapy, on-demand photothermal ablation, and multimodal imaging guidance into a single platform, offering a rational and promising integrated strategy to overcome the key limitations of conventional TACE for advanced HCC management.

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BibTeX
@article{zhang2026agaroseencapsulated,
  title = {{Agarose-Encapsulated Multifunctional Microspheres with High Drug Payload and Multimodal Imaging Capability for Arterial Embolization–Associated Hyperthermia Therapy}},
  author = {Yuqing Zhang and Shuo Huang and Quanming Kou and Yindong Xu and Yizhou Xu and Lei Chen and Xiangyue Wang and Changsheng Shi},
  journal = {Molecules},
  year = {2026},
  month = oct,
  doi = {10.3390/molecules31203626},
  url = {https://www.mdpi.com/1420-3049/31/20/3626},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Agarose-Encapsulated Multifunctional Microspheres with High Drug Payload and Multimodal Imaging Capability for Arterial Embolization–Associated Hyperthermia Therapy
AU  - Yuqing Zhang
AU  - Shuo Huang
AU  - Quanming Kou
AU  - Yindong Xu
AU  - Yizhou Xu
AU  - Lei Chen
AU  - Xiangyue Wang
AU  - Changsheng Shi
PY  - 2026
DA  - 2026/10/01
JO  - Molecules
DO  - 10.3390/molecules31203626
UR  - https://www.mdpi.com/1420-3049/31/20/3626
AB  - Hepatocellular carcinoma (HCC) represents a leading cause of cancer-related mortality worldwide, and transarterial chemoembolization (TACE) remains the standard first-line locoregional therapy for intermediate-stage HCC. Nevertheless, conventional TACE frequently yields suboptimal therapeutic efficacy in advanced or heterogeneous tumors, necessitating combined therapeutic strategies. Herein, we report a one-step emulsion fabrication strategy to develop agarose-encapsulated multifunctional microspheres (AEMMs) using low-cost, biocompatible agarose as the scaffold matrix. AEMMs co-encapsulate PSS for electrostatic drug binding, iodixanol as a dual-contrast agent for CT and DSA, and superparamagnetic Fe3O4 nanoparticles that serve as both MRI contrast agent and NIR photothermal converter. In vitro evaluation demonstrates that AEMMs achieve ultrahigh drug loading capacities of 89.87 ± 1.78 mg/mL for DOX or 90.60 ± 0.84 mg/mL for Irinotecan, which are comparable to commercial CalliSpheres® and nearly twofold higher than DC Beads®. Photothermal evaluation confirms that AEMMs induce rapid temperature elevation above 50 °C within 3 min under 808 nm laser irradiation, with excellent thermal stability and reproducibility over repeated on–off cycles. Furthermore, AEMMs provide excellent complementary contrast for CT, DSA, and T2-weighted MRI, enabling real-time embolization monitoring and postoperative assessment. Blank AEMMs exhibit negligible cytotoxicity against HepG2 cells even at high concentrations, verifying favorable biocompatibility. Collectively, AEMMs integrate mechanical embolization, localized sustained chemotherapy, on-demand photothermal ablation, and multimodal imaging guidance into a single platform, offering a rational and promising integrated strategy to overcome the key limitations of conventional TACE for advanced HCC management.
SN  - 1420-3049
ER  -