Targeting drug-loaded liposomes, in addition to enhancing their therapeutic activity, enhances tumor detection and response monitoring when they are coloaded
with an imaging agent. Addition of transferrin to 10B plus iodine contrast agent coloaded liposomes allowed a 3.6-fold higher 10B concentration in tumor tissues over untargeted coloaded liposomes [375]. The selective retention of transferrin-targeted formulations led to better tumor detection 72h after administration of liposomes, a period during which the signal from untargeted liposomes had washed out, thus combining monitoring of drug delivery and tumor response with boron neutron capture Inhibitors,research,lifescience,medical therapy [375]. Combined delivery of Gd and doxorubicin in liposomes targeted with a neural cell adhesion Inhibitors,research,lifescience,medical molecule-specific peptide allowed higher concentration of doxorubicin in tumor tissues corCytoskeletal Signaling inhibitor related with increased tumor growth inhibition over untargeted coloaded liposomes together with better visualization of tumors by MRI [392]. Targeting of iron oxide and doxorubicin coloaded liposomes to pancreatic tumors by conjugation of an antimesothelin antibody improved the antitumor activity and tumor signal enhancement over untargeted liposomes [393]. Folate targeting of doxorubicin-loaded liposomes encapsulating iron oxide Inhibitors,research,lifescience,medical resulted in superior tumor growth inhibition of liver cancer tumors than the standard formulation Doxil and simultaneously allowed
tumor imaging by MRI with higher sensitivity than the commercial contrast agent, Resovist [394]. 9. Conclusions In addition to the need for extended blood Inhibitors,research,lifescience,medical circulation and stimuli-controlled extravasation to the tumor’s niche, multifunctional liposomal nanocarriers must target at least one hallmark of cancer (aberrant cell growth, drug resistance, sustained angiogenesis, and tissue invasion) for enhancement of tumor therapy and/or diagnosis. As described throughout the paper, this requires coordinated action
of stealth, targeting, and internalizing Inhibitors,research,lifescience,medical moieties to achieve intracellular delivery to cancer cells in tumors. Moreover, combined targeting of tumor cells and related neoangiogenesis is becoming a focus of research that allows destruction of both primary and unless distant tumor nodules. However, targeted therapies rely on ligands presented by a few types of tumors and must face up to the fact of the heterogeneity of tumor cells and their surface markers [175, 395, 396]. A possible direction may be the coupling of ligands of different natures (antibody, protein, peptides and chimiokine, hormone analogs) to target at least two tumor cell populations for relapse-free cancer therapy and more sensitive malignant lesion detection. Conflict of Interests The authors declare that they have no conflict of interests. Acknowledgments This work was supported by the NIH Grant U54CA151881 to V. P. Torchilin. The authors are grateful to W. C. Hartner for critical review of the paper.