A radio-theranostic nanoparticle with high specific drug loading for cancer therapy and imaging

Journal of Controlled Release : Official Journal of the Controlled Release Society
Andrew B SatterleeLeaf Huang

Abstract

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.

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Citations

Mar 24, 2016·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Edwin C PrattJan Grimm
Jul 18, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Alexandre DetappeRoss Berbeco
Nov 26, 2016·Advanced Materials·Athanasia DasargyriJean-Christophe Leroux
Jun 19, 2017·Journal of Controlled Release : Official Journal of the Controlled Release Society·Jason L J Dearling, Alan B Packard
Dec 21, 2017·Journal of Drug Targeting·Jia-Lin HuangXiao-Ling Gao
Mar 13, 2018·Drug Development and Industrial Pharmacy·Lorenzo Degli EspostiMichele Iafisco
Mar 30, 2017·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Chrysafis AndreouMoritz F Kircher
Dec 21, 2017·Chemical Society Reviews·Chao QiPeng Huang
Sep 11, 2020·Nanomaterials·Federico Boschi, Antonello Enrico Spinelli
Dec 20, 2017·ACS Nano·Christopher M HartshornPiotr Grodzinski

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