Cell-Penetrating Protein/Corrole Nanoparticles.

Area of Science:

• Biochemistry
• Materials Science
• Nanotechnology

Background:

• Metallocorroles are versatile platforms for drug development and imaging agents.
• Bioavailability and therapeutic activity are tunable via metal ion substitution and functional group modification.
• Previous studies show promise for gallium corroles in cancer treatment and imaging.

Purpose of the Study:

• To investigate the relationship between metallocorrole structure, cytotoxicity, and very low density lipoprotein (VLDL) affinity.
• To develop a novel method for preparing cell-penetrating lipophilic metallocorrole/serum-protein nanoparticles (NPs).
• To evaluate the cellular uptake and intracellular distribution of these nanoparticles in prostate cancer cells.

Main Methods:

• Synthesized and tested bis-sulfonated metallocorroles with varying metal ions (Ga, Fe, Al, Mn, Sb, Au).
• Assessed cytotoxicity and measured binding affinities to VLDL.
• Developed a nanoparticle formulation using metallocorroles and serum proteins (albumin, transferrin).
• Characterized nanoparticle size and morphology using Cryo-Transmission Electron Microscopy (Cryo-TEM).
• Performed optical imaging studies on DU-145 prostate cancer cells.

Main Results:

• Cytotoxicity of bis-sulfonated corroles increased in the order Ga < Fe < Al < Mn < Sb < Au.
• Cytotoxicity correlated positively with metallocorrole affinity for VLDL.
• Novel metallocorrole/serum-protein nanoparticles (~100 nm) were successfully prepared.
• Nanoparticles exhibited rapid cellular uptake, slow release, and distribution to ER and lysosomes in DU-145 cells.
• Transferrin-coated nanoparticles showed enhanced internalization by transferrin-receptor-rich cancer cells.

Conclusions:

• Metallocorrole cytotoxicity and VLDL binding are key factors for therapeutic potential.
• Metallocorrole/serum-protein nanoparticles offer a promising strategy to enhance bioavailability and targeting of hydrophobic drugs.
• The developed nanoparticle preparation method may be applicable to a broader range of bioactive hydrophobic molecules.