<I>In Vivo</I> Targeting of Cutaneous Melanoma Using an Melanoma Stimulating Hormone-Engineered Human Protein Cage with Fluorophore and Magnetic Resonance Imaging Tracers

Abstract

Nanoparticle (NP)-based materials are promising agents for enhancing cancer diagnosis and treatment. Once functionalized for selective targeting of tumor-expressed molecules, they can specifically deliver drugs and diagnostic molecules inside tumor cells. In the present work, we evaluated the in vivo melanoma-targeting ability of a nanovector (HFt-MSH-PEG) based on human protein ferritin (HFt), functionalized with both melanoma-targeting melanoma stimulating hormone (α-MSH) and stabilizing poly(ethylene glycol) (PEG) molecules. Independent and complementary techniques, such as whole-specimen confocal microscopy and magnetic resonance imaging, were used to detect in vivo localization of NP constructs with suitable tracers (i.e., fluorophores or magnetic metals). Targeted HFt-MSH-PEG NPs accumulated persistently at the level of primary melanoma and with high selectivity with respect to other organs. Melanoma localization of untargeted HFt-PEG NPs, which lack the α-MSH moiety, was less pronounced. Furthermore, HFt-MSH-PEG NPs accumulated to a significantly lower extent and with a different distribution in a diverse type of tumor (TS/A adenocarcinoma), which does not express α-MSH receptors. Finally, in a spontaneous lung metastasis model, HFt-MSH-PEG NPs localized at the metastasis level as well. These results suggest that HFt-MSH-PEG NPs are suitable carriers for selective in vivo delivery of diagnostic or therapeutic agents to cutaneous melanoma.

Functional ferritin nanoparticles for biomedical applications

“…Ferritin cage can serve as a multifunctional platform for the loading of metal nanoparticles and can be engineered for use as a cell-specific targeting moiety. Cell-targeting moieties can be exposed on the exterior surface of protein cage architectures by means of both genetic and chemical modifications [7,125,126]. …”

Use of Ferritin-Based Metal-Encapsulated Nanocarriers as Anticancer Agents

“…Labeling of exposed amines of HFt with rhodamine was performed as previously described [30]. Briefly, HFt solution (2 mg/mL) was incubated with 1 mM of 5(6)-carboxytetramethylrhodamine N-succinimidyl ester (λ ex 552 nm, λ em 575 nm; Thermo Fisher Scientific, Waltham, MA, USA) in PBS for 2 h at pH 7.5 and room temperature under stirring in the dark.…”

Humanized archaeal ferritin as a tool for cell targeted delivery

“…Ferritins external and internal surfaces are chemically and genetically modifiable allowing for the attachment site for drugs, nucleic acids, fluorophores or magnetic moieties. Along this line, recent studies further established heavy (H) or light (L)-chain homopolymers as versatile multifunctional nanocarriers for targeted cancer diagnosis and therapy (6)(7)(8)(9)(10). In fact, human ferritins constitute biocompatible nanocarriers that stabilize and shelter the enclosed particles, thus preventing immunogenic responses.…”