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Targeted temperature sensitive magnetic liposomes for thermo-chemotherapy

Pradhan, Pallab and Giri, Jyotsnendu and Rieken, Finn and Koch, Christian and Döblinger, Markus and Banerjee, Rinti and Bahadur, Dhirendra and Plank, Christian (2010) Targeted temperature sensitive magnetic liposomes for thermo-chemotherapy. Journal of Controlled Release, 142 (1). pp. 108-121. ISSN 0168-3659.

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We describe folate receptor targeted thermosensitive magnetic liposomes, which are designed to combine features of biological and physical (magnetic) drug targeting for use in magnetic hyperthermia-triggered drug release. The optimized liposome formulation DPPC:cholesterol:DSPE-PEG_(2000):DSPE-PEG_(2000)-Folate at 80:20:4.5:0.5 molar ratio showed calcein release of about 70% both in PBS and in 50% FBS (fetal bovine serum) at 43 °C and less than 5% release at 37 °C following 1 h incubation. Folate-targeted doxorubicin-containing magnetic liposomes of the above lipid composition (MagFolDox) showed encapsulation efficiencies of about 85% and 24% for doxorubicin and magnetic nanoparticles (mean crystallite size 10 nm), respectively. This magnetic formulation displayed the desired temperature sensitivity with 52% doxorubicin release in 50% fetal bovine serum (FBS) following 1 h incubation at 43 °C. MagFolDox, when physically targeted to tumor cells in culture by a permanent magnetic field yielded a substantial increase in cellular uptake of doxorubicin as compared to Caelyx® (a commercially available liposomal doxorubicin preparation), non-magnetic folate-targeted liposomes (FolDox) and free doxorubicin in folate receptor expressing tumor cell lines (KB and HeLa cells). This resulted in a parallel increase in cytotoxicity over Caelyx® and FolDox. Magnetic hyperthermia at 42.5 °C and 43.5 °C synergistically increased the cytotoxicity of MagFolDox. The results suggest that an integrated concept of biological and physical drug targeting, triggered drug release and hyperthermia based on magnetic field influence can be used advantageously for thermo-chemotherapy of cancers.

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Additional Information:© 2009 Elsevier. Received 13 May 2009; accepted 1 October 2009. Available online 9 October 2009. Financial supports from the German Excellence Initiative via the “Nanosystems Initiative Munich (NIM)” and the nanomission of DST, Govt. of India are gratefully acknowledged. Pallab Pradhan gratefully acknowledges DAAD (Deutscher Akademischer Austausch Dienst) for awarding the “DAAD Sandwich fellowship” for pursuing the research in Germany. David Schaffert, Ludwig-Maximilians-University of Munich is duly acknowledged for assistance with NMR and mass spectrometry. Stefan Bössinger, University of Augsburg, is duly acknowledged for DSC measurements. Dr. Jürgen Plitzko and Ulrike Boehm, Max Planck Institute of Biochemistry, Martinsried, are acknowledged for performing the Cryo-TEM studies.
Funding AgencyGrant Number
German Excellence Initiative via Nanosystems Initiative Munich (NIM)UNSPECIFIED
Deutscher Akademischer Austausch Dienst (DAAD) Sandwich fellowshipUNSPECIFIED
Subject Keywords:Targeted; Temperature sensitive; Magnetic liposomes; Magnetic nanoparticles; Hyperthermia; Drug targeting; Magnetic drug targeting; Folate receptor targeting
Issue or Number:1
Record Number:CaltechAUTHORS:20100405-102432539
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:17851
Deposited By: Tony Diaz
Deposited On:07 Apr 2010 17:55
Last Modified:03 Oct 2019 01:34

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