Multi‐Bioinspired MOF Delivery Systems from Microfluidics for Tumor Multimodal Therapy

Abstract Metal–organic framework (MOF)‐based drug delivery systems have demonstrated values in oncotherapy. Current research endeavors are centralized on the functionality enrichment of featured MOF materials with designed versatility for synergistic multimodal treatments. Here, inspired by the multifarious biological functions including ferroptosis pattern, porphyrins, and cancer cell membrane (CCM) camouflage technique, novel multi‐biomimetic MOF nanocarriers from microfluidics are prepared. The Fe3+, meso‐tetra(4‐carboxyphenyl)porphine and oxaliplatin prodrug are incorporated into one MOF nano‐system (named FeTPt), which is further cloaked by CCM to obtain a “Trojan Horse”‐like vehicle (FeTPt@CCM). Owing to the functionalization with CCM, FeTPt@CCM can target and accumulate at the tumor site via homologous binding. After being internalized by cancer cells, FeTPt@CCM can be activated by a Fenton‐like reaction as well as a redox reaction between Fe3+ and glutathione and hydrogen peroxide to generate hydroxyl radical and oxygen. Thus, the nano‐platform effectively initiates ferroptosis and improves photodynamic therapy performance. Along with the Pt‐drug chemotherapy, the nano‐platform exhibits synergistic multimodal actions for inhibiting cancer cell proliferation in vitro and suppressing tumor growth in vivo. These features indicate that such a versatile biomimetic MOF delivery system from microfluidics has great potential for synergistic cancer treatment.


Figure S1 .
Figure S1.(a) Photographs of the microfluidic platform for the preparation of MOFs; the right image shows the capillary microfluidic chip.(b) Schematic illustration of the microfluidic platform for the preparation of FeT.

Figure S9 .
Figure S9.(a) Fluorescence spectra of SOSG incubated with FeT and irradiated with a 670 nm laser for different times.(b) Fluorescence spectra of SOSG incubated with FeTPt and without 670 nm laser irradiation.

Figure S10 .
Figure S10.(a) Fluorescence spectra of SOSG incubated with H2O2 and with 670 nm laser irradiation.(b) Fluorescence spectra of SOSG incubated with FeT and then being irradiated by a 670 nm laser.(c) Fluorescence spectra of SOSG incubated with FeT plus H2O2 and then being irradiated by a 670 nm laser.(d) Fluorescence spectra of SOSG incubated with FeTPt and then being irradiated by 670 nm laser.(e) Fluorescence spectra of SOSG incubated with FeTPt plus H2O2 and then being irradiated by a 670 nm laser.

Figure S12 .
Figure S12.UV-Vis spectra of the catalyzed oxidation of TMB treated with FeT plus H2O2.

Figure S14 .
Figure S14.Hydrodynamic size distributions and PDI analyses of FeT in 7 days.

Figure S17 .
Figure S17.(a) Pt and Fe release profiles of FeTPt in PBS with different pH values.(b) Pt and Fe release profiles of FeTPt and FeTPt@CCM in DMEM containing FBS (10%).

Figure S18 .
Figure S18.Fluorescence images of 4T1 cells after various treatments and incubated with DCFH-DA to detect intracellular ROS.Scale bar = 50 µm.

Figure S20 .
Figure S20.Live/dead staining of 4T1 cells after various treatments for 24 h and stained by Calcein AM and PI.Scale bar = 100 µm.

Figure S21 .
Figure S21.Quantification analyses of fluorescence intensity of tumors after injection with FeTPt or FeTPt@CCM at different time points.

Figure S22 .
Figure S22.Biodistribution of Pt in tumors and major organs of 4T1-tumor-bearing mice after injection with FeTPt (a) or FeTPt@CCM (b) at different time points.

Figure S23 .
Figure S23.(a) Tumor growth curves after various treatments.(b) Image of tumors isolated from tumor-bearing mice at the end of the treatment.(c) Weight of tumors collected from mice at the end of the treatment.(d) Body weights of mice during the treatments.

Table S1 .
The Fe and Pt contents in different nanoparticles.