A radio-theranostic nanoparticle with high specific drug loading for cancer therapy and imaging.
We have developed a theranostic nanoparticle delivering the model radionuclide (177)Lu based on the versatile lipid-calcium-phosphate (LCP) nanoparticle delivery platform. Characterization of (177)Lu-LCP has shown that radionuclide loading can be increased by several orders of magnitude without affecting the encapsulation efficiency or the morphology of (177)Lu-LCP, allowing consistency during fabrication and overcoming scale-up barriers typical of nanotherapeutics. The choice of (177)Lu as a model radionuclide has allowed in vivo anticancer therapy in addition to radiographic imaging via the dual decay modes of (177)Lu. Tumor accumulation of (177)Lu-LCP was measured using both SPECT and Cerenkov imaging modalities in live mice, and treatment with just one dose of (177)Lu-LCP showed significant in vivo tumor inhibition in two subcutaneous xenograft tumor models. Microenvironment and cytotoxicity studies suggest that (177)Lu-LCP inhibits tumor growth by causing apoptotic cell death via double-stranded DNA breaks while causing a remodeling of the tumor microenvironment to a more disordered and less malignant phenotype.
Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7571, USA; UNC and NCSU Joint Department of Biomedical Engineering, Chapel Hill, NC 27599, USA.
Andrew B
AB
Satterlee
Biomedical Research Imaging Center, Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7571, USA.
Hong
H
Yuan
Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7571, USA; UNC and NCSU Joint Department of Biomedical Engineering, Chapel Hill, NC 27599, USA. Electronic address: leafh@unc.edu.
Leaf
L
Huang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002130:Calcium Phosphates / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004249:DNA Damage; D005260:Female; D006801:Humans; D008187:Lutetium / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000008:administration & dosage* / Q000627:therapeutic use; D009369:Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D011868:Radioisotopes / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000068936:Theranostic Nanomedicine; D015899:Tomography, Emission-Computed, Single-Photon; D059016:Tumor Microenvironment / Q000187:drug effects
D002130:Calcium Phosphates; D011868:Radioisotopes; D008187:Lutetium; C020243:calcium phosphate
Cancer; High specific drug loading; Nanoparticle; Theranostic