Nanoscale metal-organic frameworks for combined photodynamic & radiation therapy in cancer treatment

Biomaterials. 2016 Aug:97:1-9. doi: 10.1016/j.biomaterials.2016.04.034. Epub 2016 Apr 26.

Abstract

Nanoscale metal organic frameworks (NMOFs) have shown great potential in biomedicine owing to their structural/chemical diversities, high molecular loading capacities, and intrinsic biodegradability. Herein, we report the rational design of a NMOF composed by hafnium (Hf(4+)) and tetrakis (4-carboxyphenyl) porphyrin (TCPP). In such Hf-TCPP NMOFs, while TCPP is a photosensitizer to allow photodynamic therapy (PDT), Hf(4+) with strong X-ray attenuation ability could serve as a radio-sensitizer to enhance radiotherapy (RT). Those NMOFs with polyethylene glycol (PEG) coating show efficient tumor homing upon intravenous injection, and thus could be used for in vivo combined RT & PDT, achieving a remarkable anti-tumor effect. Importantly, Hf-TCPP NMOFs show efficient clearance from the mouse body, minimizing concerns regarding their possible long-term toxicity. Our work thus presents a new concept of developing multifunctional NMOFs as a biodegradable carrier-free system, in which both metal ions and organic ligands are fully utilized to exert their therapeutic functions.

Keywords: Combination therapy; Nanoscale metal−organic framework; Photodynamic therapy; Radiation therapy.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Hafnium / chemistry
  • Humans
  • Injections, Intravenous
  • Metal-Organic Frameworks / chemistry*
  • Metalloporphyrins / therapeutic use
  • Mice
  • Mice, Inbred BALB C
  • NIH 3T3 Cells
  • Nanostructures / chemistry*
  • Nanostructures / ultrastructure
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Neoplasms / radiotherapy*
  • Photochemotherapy*
  • Polyethylene Glycols / chemistry

Substances

  • 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin cobalt
  • Metal-Organic Frameworks
  • Metalloporphyrins
  • Polyethylene Glycols
  • Hafnium