Osteotropic Radiolabeled Nanophotosensitizer for Imaging and Treating Multiple Myeloma.
basic_science · Level V
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- Record sourced from PubMed, PMID 32223222.
- Also identified by DOI 10.1021/acsnano.9b09618 and PMC identifier 7295119.
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Abstract
Rapid liver and spleen opsonization of systemically administered nanoparticles (NPs) for <i>in vivo</i> applications remains the Achilles' heel of nanomedicine, allowing only a small fraction of the materials to reach the intended target tissue. Although focusing on diseases that reside in the natural disposal organs for nanoparticles is a viable option, it limits the plurality of lesions that could benefit from nanomedical interventions. Here we designed a theranostic nanoplatform consisting of reactive oxygen (ROS)-generating titanium dioxide (TiO<sub>2</sub>) NPs, coated with a tumor-targeting agent, transferrin (Tf), and radiolabeled with a radionuclide (<sup>89</sup>Zr) for targeting bone marrow, imaging the distribution of the NPs, and stimulating ROS generation for cell killing. Radiolabeling of TiO<sub>2</sub> NPs with <sup>89</sup>Zr afforded thermodynamically and kinetically stable chelate-free <sup>89</sup>Zr-TiO<sub>2</sub>-Tf NPs without altering the NP morphology. Treatment of multiple myeloma (MM) cells, a disease of plasma cells originating in the bone marrow, with <sup>89</sup>Zr-TiO<sub>2</sub>-Tf generated cytotoxic ROS to induce cancer cell killing <i>via</i> the apoptosis pathway. Positron emission tomography/X-ray computed tomography (PET/CT) imaging and tissue biodistribution studies revealed that <i>in vivo</i> administration of <sup>89</sup>Zr-TiO<sub>2</sub>-Tf in mice leveraged the osteotropic effect of <sup>89</sup>Zr to selectively localize about 70% of the injected radioactivity in mouse bone tissue. A combination of small-animal PET/CT imaging of NP distribution and bioluminescence imaging of cancer progression showed that a single-dose <sup>89</sup>Zr-TiO<sub>2</sub>-Tf treatment in a disseminated MM mouse model completely inhibited cancer growth at euthanasia of untreated mice and at least doubled the survival of treated mice. Treatment of the mice with cold Zr-TiO<sub>2</sub>-Tf, <sup>89</sup>Zr-oxalate, or <sup>89</sup>Zr-Tf had no therapeutic benefit compared to untreated controls. This study reveals an effective radionuclide sensitizing nanophototherapy paradigm for the treatment of MM and possibly other bone-associated malignancies.
Medical subject headings
- Multiple Myeloma