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

Purpose: As a promising photodynamic therapy (PDT) agent, Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS 4 ) 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 AlPcS 4 /PDT effect, the AlPcS 4 delivery sys­tems with different drug carriers were synthesized and investigated. Materials and methods: Gold nanorods, cationic liposomes, and Pluronic ® F127 nanomicellars were used to formulate the AlPcS 4 delivery systems. The anticancer effect was evaluated by CCK-8 assay and colony formation assay. The delivery efficiency of AlPcS 4 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 ([Ca 2+ ] i ) concentration were further measured to evaluate the mechanism of cell death. Results: The series of synthesized AlPcS 4 delivery sys­tems with different drug carriers improve the limited PDT effect in varying degrees. In contrast, AlPcS 4 complex with gold nanorods has significant anticancer effects because gold nanorods are not only suitable for AlPcS 4 delivery, but also exhibit enhanced singlet oxygen generation effect and photothermal effect to induce cell death directly. Moreover, AlPcS 4 complex with cationic liposomes shows the potent inhibition effect because of its optimal AlPcS 4 delivery efficiency and ability to block serum albumin. In addition, AlPcS 4 complex with Pluronic F127 exhibits infe­rior PDT effect but presents lower cytotoxicity, slower dissociation rate, and longer retention time of incorporated drugs; thus, F127–AlPcS 4 is used for prolonged gastric cancer therapy. Conclusion: The described AlPcS 4 drug delivery systems provide promising agents for gastric cancer therapy. Keywords: drug delivery carriers, AlPcS 4 , gastric cancer therapy, gold nanoparticles, cationic liposome, nanomicelle