The use of pH-triggered leaky heterogeneities on rigid lipid bilayers to improve intracellular trafficking and therapeutic potential of targeted liposomal immunochemotherapy Journal Article
| Authors: | Karve, S.; Alaouie, A.; Zhou, Y.; Rotolo, J.; Sofou, S. |
| Article Title: | The use of pH-triggered leaky heterogeneities on rigid lipid bilayers to improve intracellular trafficking and therapeutic potential of targeted liposomal immunochemotherapy |
| Abstract: | During endocytosis, pH-triggered release of encapsulated therapeutics from delivery carriers may accelerate their intracellular trafficking increasing therapeutic efficacy. To improve the therapeutic potential of targeted immunochemotherapy using anti-HER2/neu liposomal doxorubicin, we exploit the formation of leaky heterogeneities on rigid lipid bilayers to extensively release doxorubicin during endocytosis. We have previously demonstrated that pH-dependent formation of phase-separated lipid heterogeneities on the plane of a bilayer membrane increases the permeability of bilayers when they are composed of lipid pairs with rigid non-matching acyl chain lengths. This was suggested to be due to defective packing among lipids residing at the interfaces of lipid domains. Here we design nanometer-size antiHER2/neu-labeled PEGylated vesicles composed of lipid pairs with longer non-matching acyl chain lengths (n = 18 and 21). These vesicles exhibit superior killing efficacy of cancer cells compared to established liposome formulations, and their killing efficacy is similar to the effect of combined free doxorubicin and free antiHER2/neu antibody. Other transport-related properties such as liposome blood circulation times, and specific binding and internalization by cancer cells are unaffected. These results demonstrate the potential of vesicles with pH-triggered leaky heterogeneities to increase the therapeutic potential of targeted immunochemotherapy. © 2009 Elsevier Ltd. All rights reserved. |
| Keywords: | controlled study; human cell; doxorubicin; combined modality therapy; chemotherapy; binding affinity; animals; mice; lipid; ph; intracellular transport; drug screening assays, antitumor; cell line, tumor; mice, inbred balb c; drug delivery systems; immunotherapy; cardiovascular system; cancer cell; cell membrane; cell membranes; nanoparticle; lipids; drug therapy; trastuzumab; endocytosis; epidermal growth factor receptor antibody; liposome; heterogeneous membranes; immunochemotherapy; ph-triggered; acyl chain; bi-layer; bilayer membranes; blood circulation; cancer cells; intracellular trafficking; lipid domains; liposomal doxorubicin; nanometer size; ph-dependent; specific binding; therapeutic efficacy; therapeutic potentials; triggered release; chain length; ion exchange membranes; labels; liposomes; phase interfaces; lipid bilayers; drug carrier; immunoliposome; pentetate indium in 111; phosphatidic acid; phosphatidylcholine; bilayer membrane; cell killing; circulation time; encapsulation; internalization; lipid bilayer; lipid vesicle; membrane permeability; hydrogen-ion concentration; polyethylene glycols |
| Journal Title: | Biomaterials |
| Volume: | 30 |
| Issue: | 30 |
| ISSN: | 0142-9612 |
| Publisher: | Elsevier |
| Date Published: | 2009-10-01 |
| Start Page: | 6055 |
| End Page: | 6064 |
| Language: | English |
| DOI: | 10.1016/j.biomaterials.2009.07.038 |
| PUBMED: | 19665223 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 3" - "Export Date: 30 November 2010" - "CODEN: BIMAD" - "Source: Scopus" |
