Protoporphyrin IX (PpIX)‐Coated Superparamagnetic Iron Oxide Nanoparticle (SPION) Nanoclusters for Magnetic Resonance Imaging and Photodynamic Therapy

Abstract

The ability to produce nanotherapeutics at large-scale with high drug loading efficiency, high drug loading capacity, high stability, and high potency is critical for clinical translation. However, many nanoparticle-based therapeutics under investigation suffer from complicated synthesis, poor reproducibility, low stability, and high cost. In this work, a simple method for preparing multifunctional nanoparticles is utilized that act as both a contrast agent for magnetic resonance imaging and a photosensitizer for photodynamic therapy for the treatment of cancer. In particular, the photosensitizer protoporphyrin IX (PpIX) is used to solubilize small nanoclusters of superparamagnetic iron oxide nanoparticles (SPIONs) without the use of any additional carrier materials. These nanoclusters are characterized with a high PpIX loading efficiency; a high loading capacity, stable behavior; high potency; and a synthetic approach that is amenable to large-scale production. In vivo studies of photodynamic therapy (PDT) efficacy show that the PpIX-coated SPION nanoclusters lead to a significant reduction in the growth rate of tumors in a syngeneic murine tumor model compared to both free PpIX and PpIX-loaded poly(ethylene glycol)-polycaprolactone micelles, even when injected at 1/8th the dose. These results suggest that the nanoclusters developed in this work can be a promising nanotherapeutic for clinical translation.

Indocyanine Green–Coated Gold Nanoclusters for Photoacoustic Imaging and Photothermal Therapy

“…Recently, we reported several novel fluorophore-based nanoparticle structures wherein a dye-ICG, protoporphyrin IX, or chlorin e6-was combined with only one other common component: superparamagnetic iron oxide nanoparticles (SPIOs). [21][22][23] In these three structures, the amphiphilic dye molecules were utilized as an outer coating to stabilize clusters of hydrophobic SPIO particles, thereby thermodynamically driving ICG to remain bound in large concentrations. The ICG-SPIO nanoclusters were successfully employed in image-guided surgery based on PA imaging (of ICG) and pre-surgical magnetic resonance (MR) imaging (of SPIOs).…”

Recent Progress in Metal-Based Nanoparticles Mediated Photodynamic Therapy

“…These nanoparticles can affect certain target tissues in the body, without having a toxic effect on healthy tissues. In order to control and contain these particles, an adjustable magnetic field orientation is applied [ 127 ]. Toxicity of oxide nanoparticles is low in comparison with metal nanoparticles, therefore they are used for realization of unique methods, such as delivery vehicles in thermal therapy, when heated by laser or microwave radiation to the destruction temperature of the pathological tissue, etc.…”

Broaden sources and reduce expenditure: Tumor-specific transformable oxidative stress nanoamplifier enabling economized photodynamic therapy for reinforced oxidation therapy

“…However, the lacking tumor selectivity and poor water solubility of PpIX, seriously restrict its clinical application. Great efforts have been devoted to solving these issues and various versatile nanocarriers such as polymeric nanoparticles 13 , 14 , micelles 15 , 16 , liposomes 17 , peptide-based nanoparticles 18 , 19 and inorganic nanoparticles 20 , have been fabricated to enhance photosensitivity and delivery efficiency of PpIX for improved PDT. However, these delivery strategies mainly emphasize how to increase the cellular internalization of administrated PpIX for enhanced intracellular ROS generation, while the subsequent intracellular elimination of PpIX seems to be overlooked.…”