ABSTRACT
BACKGROUND: Chemo-immunotherapy modifies the tumor microenvironment to enhance the immune response and improve chemotherapy. This study introduces a dual-armed chemo-immunotherapy strategy combating breast tumor progression while re-polarizing Tumor-Associated Macrophage (TAM) using prodigiosin-loaded mannan-coated magnetic nanoparticles (PG@M-MNPs). METHODS: The physicochemical properties of one-step synthetized M-MNPs were analyzed, including X-ray diffraction, FTIR, DLS, VSM, TEM, zeta potential analysis, and drug loading content were carried out. Biocompatibility, cancer specificity, cellular uptake, and distribution of PG@M-MNPs were investigated using fluorescence and confocal laser scanning microscopy, and flow cytometry. Furthermore, the expression levels of IL-6 and ARG-1 after treatment with PG and PG@M-MNPs on M1 and M2 macrophage subsets were studied. RESULTS: The M-MNPs were successfully synthesized and characterized, demonstrating a size below 100 nm. The release kinetics of PG from M-MNPs showed sustained and controlled patterns, with enzyme-triggered release. Cytotoxicity assessments revealed an enhanced selectivity of PG@M-MNPs against cancer cells and minimal effects on normal cells. Additionally, immuno-modulatory activity demonstrates the potential of PG@M-MNPs to change the polarization dynamics of macrophages. CONCLUSION: These findings highlight the potential of a targeted approach to breast cancer treatment, offering new avenues for improved therapeutic outcomes and patient survival.
Subject(s)
Breast Neoplasms , Liver Neoplasms , Magnetite Nanoparticles , Mannose , Tumor Microenvironment , Tumor-Associated Macrophages , Breast Neoplasms/drug therapy , Breast Neoplasms/immunology , Breast Neoplasms/pathology , Humans , Female , Magnetite Nanoparticles/chemistry , Tumor-Associated Macrophages/immunology , Tumor-Associated Macrophages/drug effects , Mannose/chemistry , Liver Neoplasms/drug therapy , Liver Neoplasms/immunology , Cell Line, Tumor , Immunomodulation/drug effects , Animals , Particle Size , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Immunotherapy/methods , Mannans/chemistry , Mannans/administration & dosage , Mice , Drug Delivery SystemsABSTRACT
Biological metal-organic frameworks (BioMOFs) are hybrid compounds in which metal nodes are linked to biocompatible organic ligands and have potential for medical application. Herein, we developed a novel BioMOF modified with an anti-VEGFR1 scFv antibody (D16F7 scFv). Our BioMOF is co-loaded with a combination of an anticancer compound and a lipid-lowering drug to simultaneously suppress the proliferation, growth rate and metastases of cancer cells in cell culture model system. In particular, Prodigiosin (PG) and Simvastatin (SIM) were co-loaded into the newly synthesized Ca-Gly BioMOF nanoparticles coated with maltose and functionalized with a recombinant maltose binding protein-scFv fragment of anti-VEGFR1 (Ca-Gly-Maltose-D16F7). The nanoformulation, termed PG + SIM-NP-D16F7, has been shown to have strong active targeting behavior towards VEGFR1-overexpresing cancer cells. Moreover, the co-delivery of PG and SIM not only effectively inhibits the proliferation of cancer cells, but also prevents their invasion and metastasis. The PG + SIM-NP-D16F7 nanocarrier exhibited stronger cytotoxic and anti-metastatic effects compared to mono-treatment of free drugs and drug-loaded nanoparticles. Smart co-delivery of PG and SIM on BioMOF nanoparticles had synergistic effects on growth inhibition and prevented cancer cell metastasis. The present nanoplatform can be introduced as a promising tool for chemotherapy compared with mono-treatment and/or non-targeted formulations.
ABSTRACT
In this research, a novel composite is synthesized based on activated carbon and MIL-53(Al) through the solution mixing method at different MOF weight fractions, and the CO2 loading of prepared samples are measured in the batch and continuous apparatus. The structure, crystallinity, surface area, and chemical functionality of activated carbon, MIL-53(Al), and developed composite are characterized through BET, X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). The CO2 and N2 adsorption capacity of activated carbon, MIL-53(Al), and composites are examined in an isothermal batch reactor at the pressure range 0-110 kPa and equilibrium temperature 305 K. The adsorption isotherm of CO2 is correlated by the Langmuir and Toth models. Besides, the performance of composite is compared with MIL-53(Al) and activated carbon in a continuous packed bed at flow rate range 15-25 ml min-1 and temperature 32 °C, and the breakthrough curves are developed. The results show that increasing MOF content in the composite increases CO2 adsorption capacity, so the CO2 loading of synthesized composite containing 10%, 20%, and 30% MOF is 1.608, 1.704, and 1.792 mmol gr-1, respectively.
