Microbubble-Templated Immunoactive Metal-Phenolic Capsules for Drug Delivery and Enhanced Cancer Immunotherapy

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Immunotherapy

Background:

• Advanced drug delivery systems are crucial for improving cancer therapy outcomes.
• Integrating immunomodulatory functions into delivery systems offers synergistic therapeutic potential.
• Metal-phenolic networks (MPNs) present a versatile platform for drug encapsulation and targeted delivery.

Purpose of the Study:

• To develop novel metal-phenolic capsules for combined drug delivery and immunomodulation in cancer therapy.
• To investigate the synergistic effects of chemotherapy and immunotherapy mediated by these capsules.
• To evaluate the in vivo efficacy and immune response of the developed system.

Main Methods:

• Assembly of a stable metal-phenolic network (MPN) using Fe(III), tannic acid, and catechol-modified hyaluronic acid.
• Loading of doxorubicin (DOX) onto mannose-glycated bovine serum albumin microbubbles to form microcapsules.
• Assessment of pH-responsive DOX release, reactive oxygen species (ROS) generation, and immunogenic cell death (ICD) induction.
• In vivo evaluation using bilateral tumor models and flow cytometry analysis to assess tumor inhibition, metastasis delay, and immune cell activation.

Main Results:

• The developed microcapsules exhibited pH-responsive DOX release and induced ROS accumulation, enhancing ICD.
• The capsules effectively promoted dendritic cell (DC) maturation through direct stimulation and paracrine signaling from M1 macrophages.
• In vivo studies showed significant inhibition of primary and distant tumor growth, delayed lung metastasis, and robust T-cell responses.
• Enhanced DC maturation and increased infiltration of activated CD8+ and CD4+ T cells were confirmed in lymph nodes, tumors, and spleens.

Conclusions:

• The immunoactive MPN microcapsules provide a promising platform for synergistic cancer therapy.
• This approach enhances the immunotherapeutic efficacy of doxorubicin through combined chemotherapy and carrier-inherent immunomodulation.
• The developed system offers a novel strategy for combinatorial cancer treatment with potential for reduced metastasis.