Bioinspired Synthesis of Intrinsically ¹⁷⁷Lu-Labeled Hybrid Nanoparticles for Potential Cancer Therapy

Abstract

Intrinsically radiolabeled inorganic nanoparticles represent a new paradigm in personalized treatment of cancer. To minimize their potential side effects for future clinical translation, it is desirable to explore biocompatible materials for synthesis of the cancer-targeting nanoparticles. In this study, we report a unique human serum albumin (HSA)-mediated biomineralization process for synthesis of intrinsically radiolabeled [177Lu]­Lu2O3 nanoparticles entrapped in a protein scaffold ([177Lu]­Lu2O3-HSA nanocomposite). Various instrumental techniques such as X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS), transmission electron microscopy (TEM), etc. were utilized for characterization of as-synthesized nonradioactive nanoparticles. The intrinsically 177Lu-labeled nanoparticles demonstrated excellent in vitro and in vivo stability in preclinical settings. Cell binding and toxicity studies demonstrated the binding affinity and specificity of the intrinsically radiolabeled nanoparticles toward melanoma (B16F10) cells for use as a radiotherapeutic agent. Biodistribution studies demonstrated rapid and enhanced accumulation of the radiolabeled nanoparticles in the tumor (11.7 ± 2.1%ID/g at 4 h post-injection) with significant retention up to 7 days. The therapeutic efficacy of the [177Lu]­Lu2O3–HSA nanocomposite was demonstrated by tumor regression studies performed over a period of 21 days. The encouraging results obtained in this study demonstrate the potential of the [177Lu]­Lu2O3–HSA nanocomposite for clinical translation. This strategy will also facilitate the synthesis of other radiolabeled biocompatible nanoparticles for use in cancer theranostics.

Radiolabeled nanomaterials for biomedical applications: radiopharmacy in the era of nanotechnology

“…On the other hand, Chakravarty et al (2020) reported the synthesis and evaluation of intrinsically radiolabeled [ 177 Lu]Lu 2 O 3 NPs entrapped in a protein scaffold ([ 177 Lu] Lu 2 O 3 -HSA) through an HSA-mediated biomineralization process. [ 177 Lu]Lu 2 O 3 -HSA nanocomposite (4.1 ± 1.2 nm) was rapidly and highly accumulated in melanoma tumors after intravenous injection with significant retention up to 7 days.…”

“…Also, [ 177 administration dose (37 MBq) without degenerating liver and kidney. Besides, biochemical and hematological parameters were unaffected, and no behavioral or phenotype changes were observed (Chakravarty et al 2020). Finally, Imlimthan et al (2021) recently described a complete study about the theranostic potential of 177 Lu-labeled CNC loaded with vemurafenib, a clinically approved tyrosine kinase inhibitor, using a murine model of metastatic lung melanoma.…”

Inorganic Radiolabeled Nanomaterials in Cancer Therapy: A Review

“…Those nanomaterials possess radioluminescence properties as well as excellent chemical stability, limiting the release and accumulation of radioactive ions in the body. For instance, [ 177 Lu]­Lu 2 O 3 nanoparticles entrapped in a HSA protein scaffold were produced following a biomineralization process . A mixture of [ 177 Lu]­LuCl 3 and LuCl 3 was added to a basic solution of HSA, resulting in [ 177 Lu]­Lu 2 O 3 @HSA nanoparticles with a high radiochemical stability.…”

“…For instance, [ 177 Lu]Lu 2 O 3 nanoparticles entrapped in a HSA protein scaffold were produced following a biomineralization process. 130 A mixture of [ 177 Lu]LuCl 3 and LuCl 3 was added to a basic solution of HSA, resulting in [ 177 Lu]Lu 2 O 3 @HSA nanoparticles with a high radiochemical stability. Ex vivo biodistribution studies following intravenous injection revealed significant dose retention in the tumor.…”

Chelator-Free Radiolabeling with Theoretical Insights and Preclinical Evaluation of Citrate-Functionalized Hydroxyapatite Nanospheres for Potential Use as Radionanomedicine

“…Moreover, radiolabeling is an important strategy to visualize the pharmacokinetics of the nanoplatform when administered in vivo . Various methods of radiolabeling of nanoplatforms have been reported over the last several years. − Among them, the chelator-free radiolabeling method has its own superiority over the conventionally used strategies that require exogenous chelators to coordinate with certain radioisotopes to form stable complexes. , Sometimes, it is tricky to select the right chelator for a particular radiometal, while sometimes, radiolabeling with chelators requires stringent conditions (including elevated temperature and long incubation time), which could damage small biomolecules or antibodies conjugated to the nanoparticle surface . Moreover, in some cases, a conventional method involves potential disintegration of the radioisotope from the chelator, which would lead to transchelation to protein, giving erroneous elucidation of the result .…”