Study And Application On Photothermal Liposomes Triggered Release Of Doxorubicin Via NIR

Liposomes currently represent one of the best studied types of drug carriers, However, controlling the encapsulated drug release from liposomes both spatially and temporally still remained a challenge. Photothermal ablation (PTA) is an emerging technique that uses near-infrared (NIR) laser light-generated heat to destroy tumor cells, and presents a promising clinical application for tumor treatment. However, complete tumor eradication by PTA therapy alone is difficult because heterogeneous heat distribution can lead to sublethal thermal dose in some areas of the tumor. In this study, we provided novel thermosensitive liposomes (TSL), called’photothermal liposomes’. which contain hollow gold nanospheres (HAuNS) and doxorubicin (DOX).Hollow gold nanospheres (HAuNS), the average size distribution is35.6±1.7nm, polydispersity index is0.003. Under the irradiation of NIR laser, HAuNS can effectively turn the NIR light into heat owing to the optical characteristics of surface plasmon resonance. Our TEM image showed that after the hydrophobic modification of OMP, the hydrophobic HAuNS can attach on the lipid membrane. The DOX&HAuNS-TSL present photothermal effect and drug controlled release under NIR laser irradiation as the external stimulus. Our data indicated that when plused NIR laser, rapid and repetitive DOX release from the photothermal liposomes (DOX&HAuNS-TSL). The study in vitro release showed the accumulative release of DOX from DOX&HAuNS-TSL enhanced almost40%when irradiated with NIR laser in24h. While without the NIR laser, the total release of DOX was less than6%. The above differences could be readily achieved upon NIR laser irradiation, which could be mainly attributed to the phase transition and the increased permeability of whole liposome membrane due to the heat diffusion from HAuNS attached on the membrane.Our data also indicated the treatment of tumor cells with DOX&HAuNS-TSL followed by NIR laser irradiation showed significantly greater cytotoxicity than the treatment with DOX&HAuNS-TSL alone, DOX-TSL alone and HAuNS-TSL plus NIR laser irradiation. The significantly enhanced cytotoxicity for DOX&HAuNS-TSL plus NIR laser should be attributed three effects:1) the PTA effect,2) increased intracellular DOX concentration due to the triggered release of DOX from DOX&HAuNS-TSL, and3) a synergistic interaction between the photothermal effect and DOX’s cytotoxic effect. Furthermore, our finding of in vivo antitumor study indicated that the combination of simultaneous photothermal and chemotherapeutic effect mediated by DOX&HAuNS-TSL plus NIR laser presented a significantly higher antitumor efficacy than the PTA alone mediated by HAuNS-TSL plus NIR laser irradiation, which could be as the valuable reference and direction for the clinical application of PTA in tumor therapy.In this study, we further introduced Her2antibody to modify photothermal liposomes and prepared the immunoliposome, called DOX&HAuNS-Her2-TSL which can be specific uptaked by BT474and SKOV3cell. In the co-cultured system of BT474/A549or SKOV3/A549cells, DOX&HAuNS-Her2-TSL can specific target to BT474or SKOV3cells. Thus cause the relative survival rate of SKOV3cells decreased from47.4%to22.4%in the SKOV3/A549system; the relative survival rate of BT474cells decreased from54.3%to29.1%in the BT474/A549system. The in vivo distribution study of SKOV3/A549bearing tumor model animals showed that more DOX&HAuNS-Her2-TSL target to SKOV3tumor.In the anti-tumor pharmacodynamics study, our data Indicated that the group of DOX&HAuNS-Her2-TSL showed excellent anti-tumor effect. The great therapeutic effect attributed to active targeting of DOX&HAuNS-Her2-TSL which further maximize the combination of simultaneous photothermal and chemotherapeutic effect.