Liposomes are considered as ideal carriers for drugs and bioactive molecules, because of their encapsulation ability and biocompatible properties. To increase their usefulness, we developed two types of multifunctional liposomes by incorporating functional components into liposome membranes. We incorporated temperature-sensitive block copolymers, gadolinium chelate-attached dendron lipid and target specific ligands such as transferrin and cRGD peptide into liposomes. Incorporation of temperature-sensitive block copolymer having a phase transition temperature of about 40 �C into stable liposomes consisting of egg yolk phosphatidylcholine and cholesterol afforded highly temperature-responsive liposomes which released content above 40 �C. Incorporation of gadolinium chelate-attached dendron lipid into the liposome membranes enabled their detection in the body with MRI. In addition, incorporation of ligands to the liposomes modified biodistribution. The MRI analysis showed that conjugation of transferrin did not improve the tumor accumulation of the liposomes but the attachment of cRGD enhanced liposome accumulation in tumor. Because cRGD has high affinity to integrin which is overexpressed on endotherial cells of tumor capillaries, their specific interaction might enhance accumulation of the liposomes in the tumor tissue. These ligand-attached temperature-responsive liposomes were loaded with doxorubicin and examined their tumor suppressive effects. These liposomes were administered to colon26 tumor-bearing mice from the tail vein and the tumors were heated at 44�C for 10 min 8 h after the liposome administration. The liposomes with cRGD exhibited stronger tumor suppressive effects than those with transferrin. Probably, efficient accumulation of the liposomes with cRGD might result in the excellent therapeutic effect. We also prepared multifunctional liposomes that deliver antigenic proteins into dendritic cells and activate them at the same time by incorporating both pH-sensitive polymers and adjuvant molecules into liposome membranes. When injected into tumor-bearing mice, these liposomes induced tumor specific immunity, which caused tumor suppression effectively.

Polymer-based design of multifunctional liposomes for cancer therapy

248th National Meeting (2014)

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