Minimally invasive injection of biomimetic Nano@Microgel for in situ ovarian cancer treatment through enhanced photodynamic reactions and photothermal combined therapy

Xiaodong Ma, Wenhui Zhou, Rong Zhang, Cancan Zhang, Jiaqi Yan, Jing Feng, Jessica M. Rosenholm, Tingyan Shi, Xian Shen, Hongbo Zhang*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

10 Citations (Scopus)
35 Downloads (Pure)

Abstract

Photodynamic therapy (PDT) induces immunogenic cell death (ICD) by producing reactive oxygen species (ROS), making it an ideal method for cancer treatment. However, the extremely lower level of oxygen, short half-life of produced ROS, and limited photosensitizers accumulating in the tumor site via intravenous administration are the main reasons that limit the further application of PDT. To address these issues, we loaded the photosensitizer porphine (THPP) into biomimetic gold nanorod-mesoporous silica core-shell nanoparticles (Au-MSN NPs) to prepare Au@MSN/THPP@CM NPs. We then seeded the NPs together with catalase (CAT) into a gelatin methacryloyl (GelMA) microgel matrix to form Au@MSN-Ter/THPP@CM@GelMA/CAT microspheres consisting of biomimetic nano@microgel. The NPs and biomimetic nano@microgel exhibited enhanced photodynamic (PD) reaction and excellent photothermal conversion ability. Moreover, we further conjugated an endoplasmic reticulum (ER) targeting ligand Tosyl Ethylenediamine (Ter) on the surface of Au-MSN NPs. The results showed that both Au@MSN-Ter/THPP@CM NPs and the finally formed Au@MSN-Ter/THPP@CM@GelMA/CAT biomimetic nano@microgel induced precise and prolonged ER stress through photodynamic reactions, which stimulated the exposure of the proapoptotic calreticulin (CRT) on the cell membrane and increased the release of high mobility group box 1 (HMGB1) form the nucleus in SKOV3 cells under near-infrared (NIR) laser irradiation. Additionally, a single dose of the nano@microgel delivered through minimally invasive injection generated a significant anti-tumor effect in the SKOV3 cell line-derived orthotopic ovarian cancer mouse model through a PD and PT combination therapy. This study offers a new strategy for enhanced PDT and provides a PD/PT synergistic treatment method for ovarian cancer.
Original languageEnglish
Article number100663
Number of pages16
JournalMaterials Today Bio
Volume20
DOIs
Publication statusPublished - Jun 2023
MoE publication typeA1 Journal article-refereed

Keywords

  • Gelatin methacryloyl
  • Photodynamic treatment
  • Photothermal treatment
  • Immunogenic cell death
  • Biomimetic Nano@Microgel

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