External Magnet Improves Antitumor Effect of Vinblastine and the Suppression of Metastasis

Overview

Journal Cancer Sci

Specialty Oncology

Date 2009 May 23

PMID 19459849

Citations 5

Authors

Suman Dandamudi

Vishwesh Patil

William Fowle

Ban-An Khaw

Robert B Campbell

Affiliations

Soon will be listed here.

Abstract

The use of magnetic drug targeting (MDT) to selectively deliver chemotherapeutic drugs to tumor cells is a widely investigated approach; however, the notion of targeting tumor endothelial cells by this method is a fairly new concept. Positively-charged (cationic) liposomes have an extraordinarily high affinity for tumor vessels, but heterogeneous targeting is frequently observed. In order to improve on the overall efficiency of targeting tumor vessels, we investigated the use of an externally applied magnetic field together with magnetic cationic liposomes (MCLs) for cancer treatment. We examined the antitumor effect of the chemotherapeutic agent vinblastine loaded in MCLs, using a murine model of melanoma. Two hours following i.v. administration of MCLs, we observed significant tumor vascular uptake with use of an external magnet (15.9 +/- 6.3%) compared to no magnet (5 +/- 1.3%). The administration of vinblastine-loaded MCLs with the magnet produced a significant antitumor effect, reducing the presence of tumor nodules in preferential sites of metastasis compared to untreated and free drug control groups. CD31 immunostaining revealed a decrease in the general length of tumor blood vessels, altered vascular morphology and interruptions in the tumor vascular lining for the vinblastine-loaded MCL groups. Drug-loaded MCLs with magnetic fields may represent a promising combination approach for cancer treatment.

Citing Articles

Pathological impact and medical applications of electromagnetic field on melanoma: A focused review.

Duan Y, Wu X, Gong Z, Guo Q, Kong Y Front Oncol. 2022; 12:857068.

PMID: 35936711 PMC: 9355252. DOI: 10.3389/fonc.2022.857068.

Microfluidic Synthesis of Vinblastine-Loaded Multifunctional Particles for Magnetically Responsive Controlled Drug Release.

Huang K, Yang C, Wang Y, Wang W, Lu Y Pharmaceutics. 2019; 11(5).

PMID: 31058849 PMC: 6571913. DOI: 10.3390/pharmaceutics11050212.

Drug delivery systems and combination therapy by using vinca alkaloids.

Lee C, Huang Y, Yang C, Huang K Curr Top Med Chem. 2015; 15(15):1491-500.

PMID: 25877096 PMC: 4997956. DOI: 10.2174/1568026615666150414120547.

Carboxymethyl chitosan-folic acid-conjugated Fe3O4@SiO2 as a safe and targeting antitumor nanovehicle in vitro.

Li H, Li Z, Zhao J, Tang B, Chen Y, Hu Y Nanoscale Res Lett. 2014; 9(1):146.

PMID: 24667013 PMC: 4229976. DOI: 10.1186/1556-276X-9-146.

Suppressive effect of juzentaihoto on vascularization induced by b16 melanoma cells in vitro and in vivo.

Ishikawa S, Ishikawa T, Asano K, Fujiwara H, Okada M, Sunagawa M Evid Based Complement Alternat Med. 2011; 2012:945714.

PMID: 22110549 PMC: 3205749. DOI: 10.1155/2012/945714.

References

Gang J, Park S, Hyung W, Choi E, Wen J, Kim H . Magnetic poly epsilon-caprolactone nanoparticles containing Fe3O4 and gemcitabine enhance anti-tumor effect in pancreatic cancer xenograft mouse model. J Drug Target. 2007; 15(6):445-53. DOI: 10.1080/10611860701453901. View

Pluen A, Boucher Y, Ramanujan S, McKee T, Gohongi T, Di Tomaso E . Role of tumor-host interactions in interstitial diffusion of macromolecules: cranial vs. subcutaneous tumors. Proc Natl Acad Sci U S A. 2001; 98(8):4628-33. PMC: 31885. DOI: 10.1073/pnas.081626898. View

Strieth S, Eichhorn M, Sauer B, Schulze B, Teifel M, Michaelis U . Neovascular targeting chemotherapy: encapsulation of paclitaxel in cationic liposomes impairs functional tumor microvasculature. Int J Cancer. 2004; 110(1):117-24. DOI: 10.1002/ijc.20083. View

Fidler I . Regulation of neoplastic angiogenesis. J Natl Cancer Inst Monogr. 2001; (28):10-4. DOI: 10.1093/oxfordjournals.jncimonographs.a024251. View

Folkman J . What is the evidence that tumors are angiogenesis dependent?. J Natl Cancer Inst. 1990; 82(1):4-6. DOI: 10.1093/jnci/82.1.4. View

Babincova M, Cicmanec P, Altanerova V, Altaner C, Babinec P . AC-magnetic field controlled drug release from magnetoliposomes: design of a method for site-specific chemotherapy. Bioelectrochemistry. 2002; 55(1-2):17-9. DOI: 10.1016/s1567-5394(01)00171-2. View

Fidler I . Angiogenesis and cancer metastasis. Cancer J. 2000; 6 Suppl 2:S134-41. View

Maswadeh H, Demetzos C, Dimas K, Hatziantoniou S, Georgopoulos A, Rallis M . Accumulation of vinblastine into transfersomes and liposomes in response to a transmembrane ammonium sulfate gradient and their cytotoxic/cytostatic activity in vitro. Anticancer Res. 2001; 21(4A):2577-83. View

Folkman J . Tumor angiogenesis. Adv Cancer Res. 1985; 43:175-203. DOI: 10.1016/s0065-230x(08)60946-x. View

10.

Babincova M, Altanerova V, Lampert M, Altaner C, Machova E, Sramka M . Site-specific in vivo targeting of magnetoliposomes using externally applied magnetic field. Z Naturforsch C J Biosci. 2000; 55(3-4):278-81. DOI: 10.1515/znc-2000-3-422. View

11.

Nair S, Boczkowski D, Moeller B, Dewhirst M, Vieweg J, Gilboa E . Synergy between tumor immunotherapy and antiangiogenic therapy. Blood. 2003; 102(3):964-71. DOI: 10.1182/blood-2002-12-3738. View

12.

Dandamudi S, Campbell R . Development and characterization of magnetic cationic liposomes for targeting tumor microvasculature. Biochim Biophys Acta. 2007; 1768(3):427-38. DOI: 10.1016/j.bbamem.2006.10.006. View

13.

Ishida T, Kundu R, Yang E, Hirata K, Ho Y, Quertermous T . Targeted disruption of endothelial cell-selective adhesion molecule inhibits angiogenic processes in vitro and in vivo. J Biol Chem. 2003; 278(36):34598-604. DOI: 10.1074/jbc.M304890200. View

14.

Wu J, Lee A, Lu Y, Lee R . Vascular targeting of doxorubicin using cationic liposomes. Int J Pharm. 2007; 337(1-2):329-35. DOI: 10.1016/j.ijpharm.2007.01.003. View

15.

Suzuki M, Shinkai M, Honda H, Kobayashi T . Anticancer effect and immune induction by hyperthermia of malignant melanoma using magnetite cationic liposomes. Melanoma Res. 2003; 13(2):129-35. DOI: 10.1097/00008390-200304000-00004. View

16.

Campbell R, Ying B, Kuesters G, Hemphill R . Fighting cancer: from the bench to bedside using second generation cationic liposomal therapeutics. J Pharm Sci. 2008; 98(2):411-29. DOI: 10.1002/jps.21458. View

17.

Campbell R, Fukumura D, Brown E, Mazzola L, Izumi Y, Jain R . Cationic charge determines the distribution of liposomes between the vascular and extravascular compartments of tumors. Cancer Res. 2002; 62(23):6831-6. View

18.

Fortin-Ripoche J, Martina M, Gazeau F, Menager C, Wilhelm C, Bacri J . Magnetic targeting of magnetoliposomes to solid tumors with MR imaging monitoring in mice: feasibility. Radiology. 2006; 239(2):415-24. DOI: 10.1148/radiol.2392042110. View

19.

Nobuto H, Sugita T, Kubo T, Shimose S, Yasunaga Y, Murakami T . Evaluation of systemic chemotherapy with magnetic liposomal doxorubicin and a dipole external electromagnet. Int J Cancer. 2004; 109(4):627-35. DOI: 10.1002/ijc.20035. View

20.

BARRY J, Bookstein J, Alksne J . Ferromagnetic embolization. Experimental evaluation. Radiology. 1981; 138(2):341-9. DOI: 10.1148/radiology.138.2.7455113. View