Stable Gold Nanorods Conjugated Liposomal Podophyllotoxin Nanocomposites for Synergistic Chemo-Photothermal Cancer Therapy

As a phenyltetralin-type lignin isolated from roots and rhizomes of Podophyllum hexandrum, podophyllotoxin (POD) possesses a great deal of biological activities, especially the anticancer activity via preventing the division of cancerous cells. However, its practical clinical application as an anticancer agent is hindered by its poor water solubility and serious side effects. Herein, we enclosed the POD into the hydrophobic cavity of natural phosphatidylcholine based liposomes to improve its solubility and thus, enhance the chemotherapeutic effect. Modified gold nanorods (GNRs) were further conjugated onto the liposomal POD composite (GLP) for enhanced photothermal stability. The extinction coefficient of GLP aqueous dispersion at 808 nm was calculated to be 8.08 Lg^–1 cm^–1, and the photothermal conversion efficiency was calculated to be 46.1%. In addition, the release of POD from GLP composite was effectively triggered by NIR irradiation. Compared with the cellular viabilities in the single chemotherapy group (54.6%) and the single photothermal therapy group (66.9%), only 10.3% 4T1 cells were survived after photothermal and chemotherapy simultaneously in the GLP group after exposure to 808 nm NIR laser at an intensity of 1.0 W/cm² for 5 min. The cytotoxicity and hemolysis assay further demonstrated the excellent biocompatibility of POD based liposomal composite. Overall, the GNRs conjugated liposomal POD is a promising therapeutic nanoagent for synergistic chemo-thermal therapy.