AlPcS₄-PDT for gastric cancer therapy using gold nanorod, cationic liposome, and Pluronic^® F127 nanomicellar drug carriers

Abstract

PurposeAs a promising photodynamic therapy (PDT) agent, Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) provides deep penetration into tissue, high quantum yields, good photostability, and low photobleaching. However, its low delivery efficiency and high binding affinity to serum albumin cause its low penetration into cancer cells, further limiting its PDT effect on gastric cancer. In order to improve AlPcS4/PDT effect, the AlPcS4 delivery sys tems with different drug carriers were synthesized and investigated.Materials and methodsGold nanorods, cationic liposomes, and Pluronic® F127 nanomicellars were used to formulate the AlPcS4 delivery systems. The anticancer effect was evaluated by CCK-8 assay and colony formation assay. The delivery efficiency of AlPcS4 and the binding affinity to serum proteins were determined by fluorescence intensity assay. The apoptosis and necrosis ability, reactive oxygen species and singlet oxygen generation, mitochondrial transmembrane potential and ([Ca2+]i) concentration were further measured to evaluate the mechanism of cell death.ResultsThe series of synthesized AlPcS4 delivery systems with different drug carriers improve the limited PDT effect in varying degrees. In contrast, AlPcS4 complex with gold nanorods has significant anticancer effects because gold nanorods are not only suitable for AlPcS4 delivery, but also exhibit enhanced singlet oxygen generation effect and photothermal effect to induce cell death directly. Moreover, AlPcS4 complex with cationic liposomes shows the potent inhibition effect because of its optimal AlPcS4 delivery efficiency and ability to block serum albumin. In addition, AlPcS4 complex with Pluronic F127 exhibits inferior PDT effect but presents lower cytotoxicity, slower dissociation rate, and longer retention time of incorporated drugs; thus, F127–AlPcS4 is used for prolonged gastric cancer therapy.ConclusionThe described AlPcS4 drug delivery systems provide promising agents for gastric cancer therapy.

Effective Gold Nanoparticle-Antibody-Mediated Drug Delivery for Photodynamic Therapy of Lung Cancer Stem Cells

“…PDT can perform selective cytotoxic action toward cancer cells through the administration of a photosensitizing drug with a wavelength equal to the absorbance range of the sensitizer caused by irradiation [11]. When Oxygen (O 2 ) is available, PDT can cause tumor ischemia and starvation through indirect tumor ablation, seen by leaking of blood vessels, stopping blood flow and collapsing of blood vessels [12], and direct tumor cell destruction and local inflammatory reactions [13]. This is due to the formation of Reactive Oxygen Species (ROS) generated upon activation of the photosensitizer (PS) using light, inducing oxidative stress.…”

Drug Delivery Systems for Phthalocyanines for Photodynamic Therapy

“…MNPs are functionalized mainly by gold (AuNPs) with covalently or non-covalently conjugated PSs (62,169). These approaches have been described for MPCs, however, they are not widely used (170,171). One specific type of extensively studied solid nanoparticles is upconversion nanoparticles (UCNPs).…”

<p>A Gastric Cancer Peptide GX1-Modified Nano-Lipid Carriers Encapsulating Paclitaxel: Design and Evaluation of Anti-Tumor Activity</p>

“…8 Chemotherapy, the main treatment modality for GC exhibits poor therapeutic benefits and significant toxicity. 9,10 In fact, the five-year survival rate after comprehensive treatment has been estimated to be between 25~30%. 11,12 Within this context, new strategies able to treat malignant tumor, prolong survival period and improve quality of life are required to improve GC's therapeutic outcomes.…”