Membrane Targeted Chemotherapy with Hybrid Liposomes for Tumor Cells Leading to Apoptosis

Abstract

We have produced hybrid liposomes (HL) which can be prepared by sonication of a mixture of vesicular and micellar molecules in a buffer solution. The physical properties of HL such as size, shape, and membrane fluidity can be controlled by changing the constituents and compositional ratio. We have employed HL for chemotherapy and interesting results are as follows; (A) The uniform and stable structure of HL composed of L-α-dimyristoylphosphatidylcholine (DMPC) and polyoxyethylenedodecyl ether (C₁₂(EO)(n)) with a diameter of 80 nm was revealed. (B) The remarkable inhibitory effects of HL on the growth of various tumor cells were attained in vitro. (C) Induction of apoptosis by HL was obtained and the pathway of apoptosis induced by HL was clarified. (D) A good correlation between the membrane fluidity of HL and inhibitory effects of HL for tumor cells was obtained. (E) Significantly chemotherapeutic effects were obtained using mice model of carcinoma after the treatment with HL without any side effects in vivo. (F) In clinical applications, prolonged survival and remarkable reduction of neoplasm were attained in patients with lymphoma after the treatment with HL without any side effects after the approval of the bioethics committee.

Therapeutic Effects of Cationic Hybrid Liposomes on the Hepatic Metastasis of Colon Carcinoma Along with Apoptosis <i>in Vivo</i>

“…13) HL having larger membrane fluidity showed higher inhibitory effects on the growth of various cancer cells in vitro and in vivo. 13,[17][18][19]21,22) We have already reported pharmacokinetics of HL using normal mice and rats. [17][18][19]21,22) HL circulated in blood for 3 h after intravenous administration to normal mice, and then metabolized in the liver.…”

“…13,[17][18][19]21,22) We have already reported pharmacokinetics of HL using normal mice and rats. [17][18][19]21,22) HL circulated in blood for 3 h after intravenous administration to normal mice, and then metabolized in the liver. [17][18][19] Specific accumulation of HL including fluorescence probe into tumor cells that immunostained using carcinoembryonic antigen (CEA) as a histochemical marker of metastatic colon carcinoma in the liver of hepatic metastasis mouse models of colon carcinoma was observed using a confocal laser scanning microscope.…”

Comparison of the Interfacial Properties of Span 80 Vesicle, W/O Emulsions and Liposomes

“…Another aspect of the two-step emulsification method is to be able to incorporate a model ligand such as PEG at the second emulsification step (Figure 1(d)), making it possible to modify the model ligand only at the outer surface of the vesicles in contrast to the conventional method [22]. As shown in Figures 4 to 6, the incorporation of the PEG layer into the membranes resulted in no large variation in surface properties for both liposomes and vesicles.…”

Inhibitory Effects of Hybrid Liposomes on the Growth of Non-small Cell Lung Carcinoma Cells and Anti-invasive Activity by Ceramide Generation without any Drugs

“…The physical properties of HL such as shape, size, membrane fluidity of phase transition can be controlled by changing the constituents and compositional ratio. Remarkably high inhibitory effects of HL composed of DMPC and polyoxyethylene(n) dodecyl ethers (C 12 (EO) n ) on the growth of tumor cells in vitro [13][14][15][16][17], in vivo [17][18][19][20][21], and clinical application [22][23][24] have been obtained without drugs. We have reported HL induced apoptosis in various cancer cells including NSCLC (A549, H460, H23 and H520) cells [25].…”