Figure 6.

Targeting peptides HSP1, HSP2, and HSP4 improve the therapeutic efficacy of LD in vivo by increasing drug bioavailability. Mice bearing human LCC H460-derived xenografts with an average tumor size of (A) ~75 mm³ (n=8 in each group) or (B) ~500 mm³ (n=7 in each group) were intravenously injected with FD, LD, targeting liposomes (HSP1-LD, HSP2-LD, or HSP4-LD), or an equal volume of PBS. The administration regimens for each experiment are shown under their respective abscissae. Data points, mean tumor volumes. Error bars, SE. *, P<0.05 compared with non-targeting LD group; ***, P<0.001 compared with FD group. (C) Mice bearing human lung adenocarcinoma H1993 xenografts with an average tumor size of ~300 mm³ were intravenously injected with FD, LD, HSP1-LD, HSP2-LD, HSP4-LD (1 mg/kg, twice a week for three weeks), or an equal volume of PBS. n=7 in each group. Data points, mean tumor volumes. Error bars, SE. *, P<0.05; **, P<0.01; ***, P<0.001. All significant P values arise from comparison with the LD group. (D-E) Pharmacokinetic and pharmacodynamic analyses of LD, HSP1-LD, HSP2-LD, and HSP4-LD in H460 xenografts. At selected time points (1 hr and 24 hr) after a single dose injection (2 mg/kg), the biodistribution patterns of free form, liposomal, and targeting liposomal drug in serum (D, upper panel), tumor (D, middle panel), and normal tissues (E) were estimated by measuring doxorubicin auto-fluorescence signals. n=3 mice in each group. Auto-fluorescence signals were also detected in the nuclei of tumors (D, lower panel). *, P<0.05; **, P<0.01; ***, P<0.001; NS, no significance; Bars, mean; error bars, SD. HSP2 and HSP4 peptides selectively and significantly enhanced drug delivery to tumors and tumor nuclei. (E) Liposomal drugs have similar biodistribution patterns in normal tissues.