Supporting Information

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1 Supporting Information Se/Ru-decorated Porous Metal-Organic Framework Nanoparticles for The Delivery of Pooled sirnas to Reversing Multidrug Resistance in Taxol-resistant Breast Cancer Cells Qingchang Chen a, 1, Meng Xu a, 1, Wenjing Zheng a, Taoyuan Xu a, Hong Deng b and Jie Liu a, * a Department of Chemistry, Jinan University, Guangzhou 51632, China b Key Laboratory of Electrochemical Technology on Energy Storage and Power Generation of Guangdong Higher Education Institutes, South China Normal University, Guangzhou 56, China * Corresponding authors, tliuliu@jnu.edu.cn. Tel/Fax : These authors contributed equally S-1

2 Supporting Figures Figure S1. Transmission electron microscope images of reduced Na 2 SeO 3 in the condition of bare MIL-11 (not grafted with Cys ). (A) SeNPs are separated from MIL-11. (B) SeNPs scattered along the edge of MIL-11. (C) MIL-11 lone. (D) SeNPs alone. S-2

3 After grafted with Cys, the BET surface area, pore volume and pore size of MIL-11 exhibited a slight decrease. The Cys moleculars are assumed to be present mainly at the center of mesopore cages, leading to a slight decrease of the pore sizes, as terminal water molecules to produce Fe(III) CUSs are directed towards the center of the cages. Therefore, these results indicated that loaded in the whole phase of MIL-11, including external surface and internal surface. A Quantity Absorbed (cm 3 /g) MIL-11 Cys@MIL Relative pressure (P/P ) B Incremental pore volume MIL-11 Cys@MIL Pore diameter (nm) Figure S2. (A) Nitrogen adsorption isotherms 77K and (B) Pore-size distribution curves with adsorption volume V and pore diameter D (right) of the as-synthesized and Cys-grafted MIL-11. S-3

4 The Elemental Analysis was performed by standard protocols employing digestion in HNO 3 /HCl/H 2 O 2 and the inductively coupled plasma-atomic emission spectroscopy (ICP-AES) was used to measure Selenium and Ruthenium content. Table S1. Loading amount of Selenium/ Ruthenium (wt%) in NPs modified MIL-11(Fe). Element Se@MIL-11 Ru@MIL-11 Selenium (wt%) Ruthenium (wt%) S-4

5 The particle-sirna complexes were incubated at ph values of 7.4, and the amount of sirna released into the supernatant was determined by measuring the absorbance at 2 nm at different time points. As shown in the Figure S3, an initial burst was observed from each type of nano-sirna complexes in the first few hours, followed by a sustained release. After 12 h incubation, the cumulative sirna release from the Se@MIL-11-siRNA and Ru@MIL-11-siRNA complexes reached to 62.4% and 78.9%, respectively. Cumulative release (%) Se@MIL-11-siRNA Ru@MIL-11-siRNA Time (h) Figure S3. Profile of sirna release from Se@MIL-11-siRNA and Ru@MIL-11-siRNA complexes prepared at mass ratio of 16:1. The percentage of cumulative sirna release was measured at, 1, 2, 4, 6, 8, 12, 24 and 48 h. SiRNA: nm. Three replicate samples were used for each condition and data were shown as mean ± SD. S-5

6 A Cell Viability (%) 1 MCF-7 MCF-7/T B Cell Viability (%) MCF-7 cell Se@MIL-11 Ru@MIL-11 C Cell Viability (%) MCF-7/T cell Se@MIL-11 Ru@MIL-11 Control 1 Concentration (µg/ml) Control Concentration (µg/ml) Control 5 1 Concentration (µg/ml) Figure S4. In vitro cytotoxicity of MIL-11, Se@MIL-11 and Ru@MIL-11 to MCF-7 cell and MCF-7/T (Taxol-resistance) cell. (A) Cell viability of MCF-7 cell and MCF-7/T after 72 h incubation with MIL-11. (B) Cell viability of MCF-7 cell after 72 h incubation with Se@MIL-11 and Ru@MIL-11 at various concentrations. (C) Cell viability of MCF-7/T cell after 72 h incubation with Se@MIL-11 and Ru@MIL-11 at various concentrations. Untreated cells were used as controls. Each bar represents the mean ± SD of four experiments. S-6

7 A MCF-7 cell MCF-7/T cell B MCF-7 cell MCF-7/T cell Cell Viability Cell Viability Control Pooled sirna MIL-11 Paclitaxel Se@MIL-11-PsiRNA Se@MIL-11-VsiRNA Se@MIL-11-(P+V)siRNA Control Pooled sirna MIL-11 Paclitaxel Ru@MIL-11-PsiRNA Ru@MIL-11-VsiRNA Ru@MIL-11-(P+V)siRNA Figure S5. (A) Cytotoxicity of Se@MIL-11-siRNA delivery systems in MCF-7 and paclitaxel resistance MCF-7/T cells. (B) Cytotoxicity of Ru@MIL-11-siRNA delivery systems in MCF-7 and paclitaxel resistance MCF-7/T cells. Cells were incubated with Pooled sirna solution, paclitaxel solution (1 µg/ml), MIL-11(1 µg/ml), Se/Ru@MIL-11 (1 µg/ml) and Se/Ru@MIL-11-siRNA (weight ratio of vehicles to sirna = :1, the concentration of Se/Ru@MIL-11 is 1 µg/ml ) for 72 h, and then the cytotoxicity was determined by MTT assay. Each bar represents the mean ± SD of four experiments. S-7

8 A Intensity (a.u.) 5 3 MIL-11 B Intensity (a.u.) Se@MIL Raman shift (cm -1 ) Raman shift (cm -1 ) Figure S6. Raman-spectrum of activated MIL-11(A) and Se@MIL-11 (B). S-8

9 Table S2. Summary of Raman vibrations in MIL-11 materials Wavenumbers [cm -1 ] Vibration Comment Raman / Intensity* 37 / w Ar-H aromatic C-H vibration of Theterephthalic acid 16 / s C=C C=C stretching vibration (Benzene-body) 1489 / w C=C C=C (Benzene-body) 14 / m - Ar-CO 2 (C=O) symmetric stretching vibration 1389 / m C=C C=C (Benzene-body) 693 / w C-S C-S coupled vibration of L-cysteine 537 / w - CO 2 out-plane rocking vibration of L-cysteine 445 / w - CO 2 in-plane rocking vibration of L-cysteine 366 / m C-C-N Deformation vibration 215 / w C-C-S Deformation vibration S-9

10 Figure S7. Activation intracellular apoptotic signaling pathways by and Paclitaxel resistance MCF-7/T cells were treated with (1 µg/ml), (weight ratio of vehicles to sirna = :1, the concentration of Se/Ru@MIL-11 is 1 µg/ml) for 24 h. S-1