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Modified-Release Drug Delivery Systems: Stimuli-Activated01:30

Modified-Release Drug Delivery Systems: Stimuli-Activated

Stimuli-activated drug delivery systems are designed to release drugs in response to specific physical, chemical, or biological stimuli. These systems often utilize hydrogels—three-dimensional, hydrophilic polymer networks capable of swelling in aqueous environments and retaining significant fluid volumes. Upon exposure to particular stimuli, these hydrogels undergo structural transitions that allow the embedded drug to be released. Due to this adaptive behavior, such systems are also called...

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Injectable HMME-Loading Emulsion Hydrogel for Ultrasound-Triggered Release and Enhanced Sonodynamic Immunotherapy.

Jia Zhang1,2, Chunyu Lai1, Bin Li1

  • 1Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, #79 Qingchun Road, Hangzhou, 310003, China.

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This study developed an emulsion hydrogel loaded with hematoporphyrin monomethyl ether (HMME) to enhance sonodynamic immunotherapy for difficult-to-treat cancers. The novel hydrogel boosts anti-tumor immune responses and improves treatment efficacy when combined with immune checkpoint blockade therapies.

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HMMEemulsion hydrogelimmune checkpoint blockadesonodynamic therapy

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Area of Science:

  • Biomedical Engineering
  • Immunology
  • Oncology

Background:

  • Immune checkpoint blockade (ICB) therapies targeting PD-1/PD-L1 show limited efficacy in low-immunogenic tumors.
  • Novel strategies are needed to enhance immunotherapy for challenging cancer types.

Purpose of the Study:

  • To develop an emulsion hydrogel encapsulating hematoporphyrin monomethyl ether (HMME) for enhanced sonodynamic immunotherapy (SDT).
  • To evaluate the efficacy of this hydrogel combined with ultrasound (US) and ICB in low-immunogenic cancers.

Main Methods:

  • Fabrication of a shear-thinning, water-in-oil emulsion hydrogel for HMME encapsulation.
  • Assessment of US- and lipase-triggered HMME release kinetics.
  • In vivo evaluation of the hydrogel combined with US and anti-PD-1 therapy in a pancreatic cancer model.

Main Results:

  • The HMME-loaded hydrogel (Gel@HMME) demonstrated controlled release upon ultrasound stimulation.
  • Gel@HMME + US promoted dendritic cell maturation and M1-TAM polarization, enhancing T cell infiltration.
  • Combination therapy significantly inhibited tumor growth by upregulating calreticulin and PD-L1 expression.

Conclusions:

  • An injectable HMME-loaded emulsion hydrogel offers a promising approach for sonodynamic immunotherapy.
  • This strategy effectively enhances anti-tumor immune responses in low-immunogenic cancers.
  • The combination of SDT and ICB presents a potent therapeutic strategy for pancreatic cancer.