The biodistribution and tumor localization of SP5-2-LD, MP5-2-LD, LD, and FD were estimated by measuring the intrinsic auto-fluorescence signal of doxorubicin in mice with NSCLC xenografts. Doxorubicin (M r 543.54), a small-molecule chemotherapeutic agent as its M r is ,1000, has a poor pharmacokinetic profile, and its blood concentration drops to background level within one hour after administration ( Fig. S5A and Text S2). The pharmacokinetic profile of various liposomal doxorubicin formulations, including SP5-2-LD, MP5-2-LD, and LD, were markedly greater than FD (Fig. S5A) . The area under the concentrationtime curve (AUC 0-48 hours ) of doxorubicin in tumor tissues was 10.4 mg?hr/g, 31.5 mg?hr/g, 29.0 mg?hr/g, and 59.9 mg?hr/g in the FD, LD, MP5-2-LD, and SP5-2-LD groups, respectively (Table S2 ). The mean intra-tumor doxorubicin concentration in the SP5-2-LD-treated group was 5.7-, 1.9-and 2.1-fold higher than the intra-tumor doxorubicin concentration in the FD, LD, and MP5-2-LD groups (Fig. 4A and Table S2 ).