Cell-Penetrating Protein/Corrole Nanoparticles

Abstract

Recent work has highlighted the potential of metallocorroles as versatile platforms for the development of drugs and imaging agents, since the bioavailability, physicochemical properties and therapeutic activity can be dramatically altered by metal ion substitution and/or functional group replacement. Significant advances in cancer treatment and imaging have been reported based on work with a water-soluble bis-sulfonated gallium corrole in both cellular and rodent-based models. We now show that cytotoxicities increase in the order Ga < Fe < Al < Mn < Sb < Au for bis-sulfonated corroles; and, importantly, that they correlate with metallocorrole affinities for very low density lipoprotein (VLDL), the main carrier of lipophilic drugs. As chemotherapeutic potential is predicted to be enhanced by increased lipophilicity, we have developed a novel method for the preparation of cell-penetrating lipophilic metallocorrole/serum-protein nanoparticles (NPs). Cryo-TEM revealed an average core metallocorrole particle size of 32 nm, with protein tendrils extending from the core (conjugate size is ~100 nm). Optical imaging of DU-145 prostate cancer cells treated with corrole NPs (≤100 nM) revealed fast cellular uptake, very slow release, and distribution into the endoplasmic reticulum (ER) and lysosomes. The physical properties of corrole NPs prepared in combination with transferrin and albumin were alike, but the former were internalized to a greater extent by the transferrin-receptor-rich DU-145 cells. Our method of preparation of corrole/protein NPs may be generalizable to many bioactive hydrophobic molecules to enhance their bioavailability and target affinity.

Protein-coated corrole nanoparticles for the treatment of prostate cancer cells

“…S8). As previously reported with other corroles 15 , extraction into DCM or toluene was not observed even upon vigorous stirring or shaking of the NPs in the PBS/DCM mixture (Video 10). Next, the uptake of (2)Ga/ HSA NPs in regular media was examined by preparing NPs coated with HSA covalently modified with FITC (HSA-FITC).…”

“…S1) indicated a mean NP size of 69.2 ± 0.2 nm. Cryo-TEM analysis of (2)Ga/ HSA NPs revealed the formation of particles that were morphologically distinct from tpfc-based NPs 15 . Particles were spherical with an average diameter of 50.2 ± 8.1 nm (Fig.…”

“…The formation of (2)Ga/HSA NPs was confirmed by utilizing our previously established protocols 15 . HPLC analysis ( Fig.…”

“…Further investigation into the antineoplastic activity of metallocorroles revealed that the lipophilicity of corrole derivatives plays a central role in their activity toward malignant cells 15 . This finding led to the establishment of a facile procedure for the introduction of highly lipophilic corroles into biological media, consisting of corrole nanoparticles (NPs) coated with native proteins 15 . Independently, we also developed a novel one-pot synthesis of 5,10,15-tris(trifluoromethyl)corrole and its Ga(III) derivative, (2)Ga (Fig.…”

Corrole‐based photodynamic antitumor therapy

“…Cell morphology could reflect the health status of cells . When tumor cells undergo PDT treatment, apoptosis or necrosis typically would follow, leading eventually to cell demise through complicated and multiple processes.…”