Inhibition of SerpinB9 to enhance granzyme B-based tumor therapy by using a modified biomimetic nanoplatform with a cascade strategy

Han, Ran; Yu, Luting; Zhao, Chenxuan; Liu, Ying; Ma, Yanju; Qian, Zhiyu; Gu, Yueqing; Li, Siwen

doi:10.1016/j.biomaterials.2022.121723

Cited by 20 publications

(16 citation statements)

References 45 publications

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“…Han et al. [ 251 ] constructed biological NPs from the exosomes of M1 (M1-Exo) macrophages, used the inherent cytokines in M1-Exo to regulate the TME, and combined with PTT and gene therapy for tumor treatment. However, there are some disadvantages.…”

Section: Discussionmentioning

confidence: 99%

Cell membrane-coated nanomaterials for cancer therapy

Zeng¹,

Tang²,

Xiao³

et al. 2023

Materials Today Bio

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Section: Discussionmentioning

confidence: 99%

Cell membrane-coated nanomaterials for cancer therapy

Zeng¹,

Tang²,

Xiao³

et al. 2023

Materials Today Bio

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“…SerpinB9 protein, as an important protein involved in tumor cell apoptosis, can bind to granzyme B and downregulate its intracellular expression, thus inhibiting the apoptosis of tumor cells. 36 To evaluate the impact of SerpinB9 on granzyme B content in 4T1 cells, we employed the CRISPR/Cas9 system to knock down SerpinB9. Knockdown efficiency was verified by T7 endonuclease 1 (T7E1) mismatch detection and Western blotting (Figure 2E,F).…”

Section: Serpinb9 Is Highly Expressed In Im-and Msl-subtype Breast Ca...mentioning

confidence: 99%

Near-Infrared Titania Nanoparticle-Based Photoimmunotherapy via Tumor-Microenvironment-Responsive Gene Editing of SerpinB9 for Triple-Negative Breast Cancer

Yang,

Zhang,

Zhang

et al. 2024

ACS Appl. Nano Mater.

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Triple-negative breast cancer (TNBC) is a heterogeneous disease with multiple biological subtypes, offering poor clinical outcomes. No targeted therapy was approved for TNBC due to lack of tumor-specific targets. Here, we identify SerpinB9 as a vulnerability target for immunomodulatory TNBC tumors, suggesting that gene editing of SerpinB9 via the CRISPR/Cas9 system may be a viable approach to immunomodulatory TNBC-targeted therapy. To increase bioavailability and improve the delivery efficiency of gene editing, we designed glutathione-responsive nanoparticles to deliver Cas9 ribonucleoprotein targeting SerpinB9 (TiO 2−x @Cas9-RNP@HA). Under near-infrared light irradiation, TiO 2−x can produce both photodynamic therapy (PDT) and photothermal therapy (PTT) effects. PTT can induce tumor cell ablation and immunogenic cell death. PDT can produce ROS to induce cell killing and downregulation of SerpinB9. Inhibition of SerpinB9 expression with nanoparticles (TiO 2−x @Cas9-RNP@ HA) combined with near-infrared titania phototherapy can synergistically inhibit tumor growth. These results demonstrate the potential of near-infrared titania nanoparticle-based phototherapy and precise SerpinB9-targeted therapies in immunomodulatory TNBCs.

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“…Because these naturally occurring vesicles enclose proteins, lipids, and nucleic acids, they are promising candidates for cancer therapy, using exosomes derived from M1 macrophages (M1-Exo) to create biological NPs. 262 The intrinsic cytokines inside M1-Exo were used to orchestrate tumor microenvironment (TME) modulation in this novel strategy. This approach was successfully combined with photothermal therapy (PTT) and gene therapy, resulting in a multimodal tumor treatment strategy.…”

Section: Challenges and Possible Solutionsmentioning

confidence: 99%