Photodynamic Therapy of Aluminum Phthalocyanine Tetra Sodium 2-Mercaptoacetate Linked to PEGylated Copper–Gold Bimetallic Nanoparticles on Colon Cancer Cells

Abstract

This work reports for the first time on the synthesis, characterization, and photodynamic therapy efficacy of the novel aluminium (III) chloride 2(3), 9(10), 16(17), 23(24)-tetrakis-(sodium 2-mercaptoacetate) phthalocyanine (AlClPcTS41) when alone and when conjugated to PEGylated copper–gold bimetallic nanoparticles (PEG-CuAuNPs) as photosensitizers on colon cancer cells (Caco-2). The novel AlClPcTS41 was covalently linked to the PEG-CuAuNPs via an amide bond to form AlClPcTS41-PEG-CuAuNPs. The amide bond was successfully confirmed using FTIR while the crystal structures were studied using XRD. The morphological and size variations of the PEG-CuAuNPs and AlClPcTS41-PEG-CuAuNPs were studied using TEM, while the hydrodynamic sizes and polydispersity of the particles were confirmed using DLS. The ground state electron absorption spectra were also studied and confirmed the typical absorption of metallated phthalocyanines and their nanoparticle conjugates. Subsequently, the subcellular uptake, cellular proliferation, and PDT anti-tumor effect of AlClPcTS41, PEG-CuAuNPs, and AlClPcTS41-PEG-CuAuNPs were investigated within in vitro Caco-2 cells. The designed AlClPcTS41 and AlClPcTS41-PEG-CuAuNPs demonstrated significant ROS generation abilities that led to the PDT effect with a significantly decreased viable cell population after PDT treatment. These results demonstrate that the novel AlClPcTS41 and AlClPcTS41-PEG-CuAuNPs had remarkable PDT effects against Caco-2 cells and may trigger apoptosis cell death pathway, indicating the potential of the AlClPcTS41 and AlClPcTS41-PEG-CuAuNPs in enhancing the cytotoxic effect of PDT treatment.

Design consideration of phthalocyanines as sensitizers for enhanced sono-photodynamic combinatorial therapy of cancer

“…Therefore, Pcs solubility is an important factor when designing Pcs for SPDT for cancer treatments. Another method for improving the solubility of Pcs include use of polar substituents such as —SO 3 − 92 , 93 , or —CO 2 − 94 , or —OH 95 and other ionic moieties 96 , 97 .…”

Nano‐phototherapy: Favorable prospects for cancer treatment

“…Development of multi‐functional and microorganism‐based integrated PDT microsystems to improve the PDT results and great biocompatibility has revealed the bright future of tumor PDT in clinics (Huo et al, 2021). Aluminium (III) chloride 2(3), 9(10), 16(17), 23(24)‐tetrakis‐(sodium 2‐mercaptoacetate) phthalocyanine (AlClPcTS41) and AlClPcTS41‐PEGylated copper–gold bimetallic nanoparticles (PEG‐CuAu NPs) (AlClPcTS41‐PEGCuAuNPs) demonstrated impressive PDT effect against Caco‐2 cells could initiate the apoptotic pathway, showing their potential to increase cytotoxic effect of PDT treatment (Simelane et al, 2023). Additionally, when compared to unconjugated aluminum phthalocyanine (AlPcS4Cl) and their controls, the nanoconjugate significantly increased cytotoxicity and apoptosis and dramatically decreased melanoma growth and survival.…”

“…The use of nanocarriers with FA functionality improved this impact. copper-gold bimetallic nanoparticles (PEG-CuAu NPs) (AlClPcTS41-PEGCuAuNPs) demonstrated impressive PDT effect against Caco-2 cells could initiate the apoptotic pathway, showing their potential to increase cytotoxic effect of PDT treatment (Simelane et al, 2023). Additionally, when compared to unconjugated aluminum phthalocyanine (AlPcS4Cl) and their controls, the nanoconjugate significantly increased cytotoxicity and apoptosis and dramatically decreased melanoma growth and survival.…”

Photodynamic Therapy for Inflammatory and Cancerous Diseases of the Intestines: Molecular Mechanisms and Prospects for Application

“…The application of nanomedicine is instrumental in augmenting the efficacy of PDT by improving the delivery, targeting, imaging, and enabling combination therapies 171 . Nanoparticles effectively encapsulate PS, providing protection and ensuring efficient and sustained delivery to the intended site 172 .…”