Loading...

Synthesis and Characterization of Various Nanocarriers based on Metal-Organic Frameworks and their Applications in Biosensors and Drug Delivery Systems

Sojdeh, Soheil | 2025

104 Viewed
  1. Type of Document: Ph.D. Dissertation
  2. Language: Farsi
  3. Document No: 58459 (03)
  4. University: Sharif University of Technology
  5. Department: Chemistry
  6. Advisor(s): Bagherzadeh, Mojtaba; Jamali, Sirous
  7. Abstract:
  8. In this dissertation, three advanced MOF-based systems with complementary functions were designed, synthesized, characterized, and evaluated to harness the potential of these nanostructures in the fields of biosensing and cancer therapy. In the first part, a dual-mode nanosensor with a UiO-66@OPD structure was developed. By exploiting the intrinsic peroxidase-like activity of UiO-66 (Zr) and the photo-oxidation reaction of o-phenylenediamine (OPD), this system enabled highly sensitive and selective detection of hydrogen peroxide (H₂O₂), a representative reactive oxygen species (ROS). During the oxidation process, OPD was converted to OPDox, resulting in enhanced spectral signals in both the absorption region at 415 nm and the fluorescence region at 565 nm. The enzyme-like behavior of the system was confirmed by fitting to the Michaelis–Menten kinetic model, and calibration curves were obtained within the range of 0–600 nM with a high correlation coefficient (R² > 0.99). Biocompatibility assessment (MTT assay) on MCF-10A, HEK293, and A549 cell lines revealed low cytotoxicity and safe applicability for biological purposes. Owing to its high sensitivity, low cost, excellent biocompatibility, and simple design, this nanosensor demonstrates strong potential for the development of rapid diagnostic systems in biological and clinical settings. In the second part, a MIL-88A@catechin nanohybrid was constructed by employing defect engineering in MIL-88A and establishing polyphenolic networks through catechin conjugation, with the aim of serving as a targeted nanodrug for breast cancer therapy. The coordination defects in the MIL-88A framework were selectively exploited to form Fe–phenolate bonds with catechin, while surface functionalization was confirmed without disturbing crystallinity using FTIR, XRD, FESEM, XPS, and TGA analyses. Remarkably, despite the inherent antioxidant properties of catechin, this nanocomposite was able to induce strong oxidative stress in cancer cells through amplification of the Fe³⁺/Fe²⁺ redox cycle and enhanced hydroxyl radical (·OH) production via a reinforced Fenton reaction. Clinical studies demonstrated high selective cytotoxicity toward MDA-MB-231 cells (IC₅₀ = 25 μg/mL) while maintaining more than 80% viability in normal MCF-10A cells. Flow cytometry and genetic analyses (qRT-PCR) confirmed the induction of programmed cell death through both intrinsic and extrinsic apoptotic pathways, evidenced by upregulated expression of BAX, Caspase-9, and Caspase-8, alongside downregulation of BCL-2. Clinical investigations further revealed reduced tumor volume, diminished mitotic activity, increased apoptotic bodies, and modulation of angiogenesis-related receptor expression (upregulation of VEGFR1 and downregulation of VEGFR2), thereby confirming the significant antitumor efficacy of this nanocarrier in tumor suppression and angiogenesis remodeling. Overall, these findings underscore that engineered MOFs can act as multifunctional nanostructures not only for highly sensitive and accurate biosensing but also for targeted and effective treatment of therapy-resistant tumors. Such outcomes pave the way for the development of next-generation smart nanoplatforms in nanobiotechnology and nanomedicine. The third part highlights the perspective that the development of inorganic–organic hybrid nanoplatforms is regarded as a milestone in life sciences and emerging technologies, as these systems integrate the unique properties of each component while generating novel functionalities, thereby opening new horizons in diverse fields. The emergence of these new properties has facilitated enhanced drug-loading capacity, spatial selectivity, and controlled release of genes and drugs in biomedical applications. In this context, MIL-88A was employed to improve drug-loading capacity in carbon-based nanocomposites (Fe₃O₄/rGO@C₃N₄/MIL-88A). For the first time, gold (Au-HR) and silver (Ag-HR) complexes, owing to their potential in chemodynamic therapy (CDT), were stabilized within the magnetite matrix. Fenton assay results indicated that the most biocompatible nanocomposite was Fe₃O₄/rGO@C₃N₄/MIL-88A@Au-HR, which not only exhibited minimal ROS generation at physiological pH but also displayed the most favorable time-dependent pattern (92% increase within 90 min). Conversely, the Fe₃O₄/rGO@C₃N₄/MIL-88A@Ag-HR sample demonstrated a more pronounced pH-dependent response, with a 216% increase across the pH range of 0.4–4.7. From a therapeutic standpoint, the direct injection of antitumor agents into tumor tissues remains one of the most promising strategies for enhancing drug efficacy while minimizing side effects in healthy organs. In this regard, an injectable gelatin–chitosan hydrogel was selected as a promising matrix owing to its high biocompatibility, significant swelling capacity (24-fold), and excellent performance in delivering hydrophobic drugs such as paclitaxel
  9. Keywords:
  10. Metal-Organic Framework ; Nano-Biosensor ; Targeted Therapy ; Cancer Treatment ; Reactive Oxygen Species (ROS) ; Hydrogen Peroxide (H₂O₂)Detection ; Inorganic-Organic Hybrid Nanoplatform ; Fenton Reaction

 Digital Object List

 Bookmark

No TOC