Aptamer-functionalized nanoscale metal-organic frameworks for targeted photodynamic therapy

Abstract

Photodynamic therapy (PDT) has been applied in clinical cancer treatment. Here we report an aptamer-functionalized nanoscale metal-organic framework for targeted PDT. Our nanosystem can be easily prepared and successfully used for targeted PDT with a significantly enhanced therapeutic efficacy in vitro and in vivo.Methods: By combining the strong binding ability between phosphate-terminated aptamers and Zr-based nanoscale metal-organic frameworks (Zr-NMOFs) and the intercalation of photosensitizer TMPyP4 within the G-quadruplex DNA structure, TMPyP4-G4-aptamer-NMOFs were prepared. The characteristics and photodynamic performance of TMPyP4-G4-aptamer-NMOFs were examined after preparation. Then, we studied their stability, specific recognition ability, and phototoxicity in vitro. For in vivo experiments, the nanosystem was intratumorally injected into a HeLa subcutaneous xenograft tumor mouse model. After irradiation on day 0, mice were further injected with the nanosystem on day 5 and were again subjected to laser irradiation for 30 min. Tumor volumes and body weights of all mice were measured by caliper every 2 days after the treatment.Results: The nanosystem induced 90% cell death of targeted cells. In contrast, the control cells maintained about 40% cell viability at the same concentration of nanosystem. For the in vivo experiments, the nanosystem-treated group maintained more than 76% inhibition within the entire experimental period.Conclusion: We have demonstrated that our smart TMPyP4-G4-sgc8-NMOFs nanosystem can be used for targeted cancer therapy with high efficiency.

G-Quadruplex-Based Drug Delivery Systems for Cancer Therapy

“…The rational design of ligands to selectively interact, stabilize or cleave G4 structures is a promising strategy to serve as anticancer drugs in the medical field [ 111 ]. G4 structures are also able to carry anticancer drugs and its conjugation with certain nano-particles increase the loading ability and, consequently, potentiate biological effects [ 112 ]. In addition, as the above examples have shown, some aptamers can intrinsically adopt a G4 structure, which enables extra targeting.…”

Bio‐Conjugated Advanced Materials for Targeted Disease Theranostics

“…Zirconium (Zr)‐based metal–organic frameworks containing the photosensitizers TMPyP4 or porphyrin have been reported for the targeted bioimaging and PDT in human cervix cancer HeLa cells, and in vivo when conjugated with sgc8 aptamers . Other reported metallic systems include a Mn(II)‐silver aptamer cluster used for targeted MRI of PANC‐1 tumors, which utilize an aptamer for hypoxia‐inducible factors (HIFs) .…”

Review of the Biomolecular Modification of the Metal-Organ-Framework

“…In pioneering research, the biochemical surface modification of nanomaterials has been applied to biological probes and cell imaging (Wang D. et al, 2019 ). To date, MOFs have been modified on their surface to meet specific requirements and achieve biological functionalization, such as targeted delivery and localized release (Meng et al, 2018 ). These characteristics greatly improve the performance and bioutilization of MOFs (Cai et al, 2017 ; Huang et al, 2018 ).…”