Mitochondrial metabolism blockade nanoadjuvant reversed immune-resistance microenvironment to sensitize albumin-bound paclitaxel-based chemo-immunotherapy

Mitochondrial metabolism blockade nanoadjuvant reversed immune-resistance microenvironment to sensitize albumin-bound paclitaxel-based chemo-immunotherapy

Received 3 February 2024; received in revised form 15 May 2024; accepted 17 May 2024 | Zaigang Zhou, Wenjuan Luo, Chunjuan Zheng, Haoxiang Wang, Rui Hu, Hui Deng, Jianliang Shen
The supporting information for the original article provides detailed experimental data and results to support the findings of the study. The study investigates the effects of a mitochondrial metabolism blockade nano-adjuvant, TPP-TAM, on the immune-resistant microenvironment and its impact on albumin-bound paclitaxel-based chemo-immunotherapy. Key findings include: 1. **Chemical Synthesis and Characterization**: The chemical synthesis process of TAM-C6 and TPP-TAM is described, along with their 1H-NMR and HR-MS spectra. 2. **In Vitro Effects**: Western blot assays show that TPP-TAM@Alb treatment reduces the expression of PD-L1 and TGF-β proteins in 4T1 cells, indicating improved immune response. 3. **Cell Viability and Apoptosis**: The viability of 4T1 and MCF-7 cells treated with different concentrations of TAM, TPP-TAM, TPP-TAM@Alb, and PTX@Alb is evaluated, showing that TPP-TAM@Alb enhances cell death. 4. **ROS Generation and Fluorescence**: The generation of ROS and live cell fluorescence are assessed, demonstrating the therapeutic effects of TPP-TAM@Alb. 5. **Tumor Growth and Metastasis**: The growth of 4T1 tumors and the formation of lung metastases are monitored, showing that TPP-TAM@Alb effectively inhibits tumor growth and metastasis. 6. **Toxicity Assessment**: Histopathological images of organs from treated mice are provided, indicating no significant toxicity from TPP-TAM@Alb treatment. These results collectively support the potential of TPP-TAM@Alb as a promising nano-adjuvant for enhancing the efficacy of albumin-bound paclitaxel-based chemo-immunotherapy.The supporting information for the original article provides detailed experimental data and results to support the findings of the study. The study investigates the effects of a mitochondrial metabolism blockade nano-adjuvant, TPP-TAM, on the immune-resistant microenvironment and its impact on albumin-bound paclitaxel-based chemo-immunotherapy. Key findings include: 1. **Chemical Synthesis and Characterization**: The chemical synthesis process of TAM-C6 and TPP-TAM is described, along with their 1H-NMR and HR-MS spectra. 2. **In Vitro Effects**: Western blot assays show that TPP-TAM@Alb treatment reduces the expression of PD-L1 and TGF-β proteins in 4T1 cells, indicating improved immune response. 3. **Cell Viability and Apoptosis**: The viability of 4T1 and MCF-7 cells treated with different concentrations of TAM, TPP-TAM, TPP-TAM@Alb, and PTX@Alb is evaluated, showing that TPP-TAM@Alb enhances cell death. 4. **ROS Generation and Fluorescence**: The generation of ROS and live cell fluorescence are assessed, demonstrating the therapeutic effects of TPP-TAM@Alb. 5. **Tumor Growth and Metastasis**: The growth of 4T1 tumors and the formation of lung metastases are monitored, showing that TPP-TAM@Alb effectively inhibits tumor growth and metastasis. 6. **Toxicity Assessment**: Histopathological images of organs from treated mice are provided, indicating no significant toxicity from TPP-TAM@Alb treatment. These results collectively support the potential of TPP-TAM@Alb as a promising nano-adjuvant for enhancing the efficacy of albumin-bound paclitaxel-based chemo-immunotherapy.
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Understanding Mitochondrial metabolism blockade nanoadjuvant reversed immune-resistance microenvironment to sensitize albumin-bound paclitaxel-based chemo-immunotherapy