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
Supporting information for the article "Mitochondrial metabolism blockade nanoadjuvant reversed immune-resistance microenvironment to sensitize albumin-bound paclitaxel-based chemo-immunotherapy" is provided. The study investigates the effects of a nanoadjuvant that blocks mitochondrial metabolism on the immune-resistance microenvironment in order to enhance the efficacy of albumin-bound paclitaxel-based chemo-immunotherapy. The nanoadjuvant, TAM-C6 and TPP-TAM, were synthesized and characterized. The effects of TAM on the expression of AMPK, pAMPK, PD-L1, and TGF-β proteins in 4T1 cells were evaluated using western blot analysis. The 1H-NMR spectra of TAM-C6 and TPP-TAM were also provided. The generation of ROS by DCFH-DA was evaluated after treatment with PTX@Alb, TPP-TAM@Alb, or combination therapy. The viability of 4T1 cells treated with different concentrations of TAM, TPP-TAM, TPP-TAM@Alb, and PTX@Alb was assessed. The expression of Bcl-2 proteins in 4T1 cells after TPP-TAM@Alb treatment was also evaluated. The viability of MCF-7 cells treated with different concentrations of TAM, TPP-TAM, TPP-TAM@Alb, and PTX@Alb was assessed. The effects of TPP-TAM@Alb on the expression of TGF-β protein in MCF-7 cells were evaluated. The effects of TPP-TAM@Alb on the changes of pAMPK/AMPK ratio in 4T1 cells were evaluated. The quantification of PTX by HPLC after TPP-TAM@Alb or vehicle treatment was performed. The expression levels of PD-L1 and TGF-β proteins in 4T1 tumors after various treatments were quantified. The growth of breast fat pad transplanted 4T1 tumors after various treatments was evaluated. The photo of collected subcutaneous transplanted 4T1 tumors on Day 14 after different treatments was provided. The photo of collected lungs to evaluate the possibility of using TPP-TAM@Alb to inhibit the formation of 4T1 tumor lung metastasis was provided. The quantification of the numbers of 4T1 lung metastasis focus after various treatments was performed. Representative H&E images of the heart, lung, liver, spleen, and kidney collected from healthy mice at 24 h after treatment with Vehicle or TPP-TAM@Alb were provided.Supporting information for the article "Mitochondrial metabolism blockade nanoadjuvant reversed immune-resistance microenvironment to sensitize albumin-bound paclitaxel-based chemo-immunotherapy" is provided. The study investigates the effects of a nanoadjuvant that blocks mitochondrial metabolism on the immune-resistance microenvironment in order to enhance the efficacy of albumin-bound paclitaxel-based chemo-immunotherapy. The nanoadjuvant, TAM-C6 and TPP-TAM, were synthesized and characterized. The effects of TAM on the expression of AMPK, pAMPK, PD-L1, and TGF-β proteins in 4T1 cells were evaluated using western blot analysis. The 1H-NMR spectra of TAM-C6 and TPP-TAM were also provided. The generation of ROS by DCFH-DA was evaluated after treatment with PTX@Alb, TPP-TAM@Alb, or combination therapy. The viability of 4T1 cells treated with different concentrations of TAM, TPP-TAM, TPP-TAM@Alb, and PTX@Alb was assessed. The expression of Bcl-2 proteins in 4T1 cells after TPP-TAM@Alb treatment was also evaluated. The viability of MCF-7 cells treated with different concentrations of TAM, TPP-TAM, TPP-TAM@Alb, and PTX@Alb was assessed. The effects of TPP-TAM@Alb on the expression of TGF-β protein in MCF-7 cells were evaluated. The effects of TPP-TAM@Alb on the changes of pAMPK/AMPK ratio in 4T1 cells were evaluated. The quantification of PTX by HPLC after TPP-TAM@Alb or vehicle treatment was performed. The expression levels of PD-L1 and TGF-β proteins in 4T1 tumors after various treatments were quantified. The growth of breast fat pad transplanted 4T1 tumors after various treatments was evaluated. The photo of collected subcutaneous transplanted 4T1 tumors on Day 14 after different treatments was provided. The photo of collected lungs to evaluate the possibility of using TPP-TAM@Alb to inhibit the formation of 4T1 tumor lung metastasis was provided. The quantification of the numbers of 4T1 lung metastasis focus after various treatments was performed. Representative H&E images of the heart, lung, liver, spleen, and kidney collected from healthy mice at 24 h after treatment with Vehicle or TPP-TAM@Alb were provided.
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