Purpose To develop a near-infrared (NIR) light-sensitive liposome, which contains hollow gold nanospheres (HAuNS) and doxorubicin (DOX), and evaluate their potential utility for enhancing antitumor activity and controlling drug release. Methods The liposomes (DOX&HAuNS-TSL) were designed based on a thermal sensitive liposome (TSL) formulation, and hydrophobically modified HAuNS were attached onto the membrane of the liposomes. The behavior of DOX release from the liposomes was investigated by the dialysis, diffusion in agarose gel and cellular uptake of the drug. The biodistribution of DOX&HAuNS-TSL was assessed by i.v. injection in tumor-bearing nude mice. Antitumor efficacy was evaluated both histologically using excised tissue and intuitively by measuring the tumor size and weight. Results Rapid and repetitive DOX release from the liposomes (DOX&HAuNS-TSL), could be readily achieved upon NIR laser irradiation. 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 (chemotherapy alone) and HAuNS-TSL plus NIR laser irradiation (Photothermal ablation, PTA, alone). 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. Conclusions Our study could be as the valuable reference and direction for the clinical application of PTA in tumor therapy.
It is difficult for most of drug delivery system to really display a temporal and spatial release of entrapped drug once the systems are iv administrated. We hypothesized that the photothermal effect, mediated by a near-infrared (NIR) laser and hollow gold nanospheres (HAuNS), can modulate paclitaxel (PTX) release from polymer micelles, and further result in the enhanced antitumor activity of the micelles. We loaded PTX and HAuNS, which display strong plasmon absorption in the NIR region, into glycolipid-like polymer micelles with an excellent cell internalization capability. The surface of the micelles was conjugated successfully with a peptide, which has the specific-binding with EphB4, a member of the Eph family of receptor tyrosine kinases overexpressed on cell membrane of numerous tumors, to increase the delivery of PTX into tumor cells. Rapid and repetitive drug release from our polymer (HP-TCS) micelles could be readily achieved upon NIR laser irradiation. Our data demonstrated the specific-delivery of HPTCS micelles into positive-EphB4 tumors using a duel-tumor model after iv administration during the whole experiment process (1-48h). Interestingly, significantly higher uptake of the micelles by SKOV3 tumors (positive-EphB4) than A549 tumors (negtive-EphB4) was observed, with increased ratio on experiment time. However, the specific cell uptake was observed only during the short incubation time (1-4h) in vitro. Our data also indicated the treatment of tumor cells with the micelles followed by NIR laser irradiation showed significantly greater toxicity activity than the treatment with the micelles alone, free PTX and the micelles (without PTX loading) plus NIR laser irradiation. The enhanced toxicity activity to tumor cells should be attributed to the enhanced drug cellular uptake mediated by the glycolipid-like micelles, chemical toxicity of the released drug from the micelles due to the trigger of NIR laser, and the photothermal ablation under NIR laser irradiation.
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