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Nanomedicine Treatment for Brain Tumors

Principal Investigator: Julia Y. Ljubimova, MD, PhD

Researchers in the Molecular Oncology Group developed a new anti-tumor/nanomedicine drug that releases agents that slow tumor growth directly into cancer cells without affecting normal cells. Researchers developed the new drug, Polycefin, which showed significantly increased survival in animals with brain tumors who received the drug. The new drug is non-toxic, non-immunogenic, and biodegradable. Using this approach, it is possible to block several unique cancer markers that aid tumor growth for each patient at the same time, which can greatly increase the effectiveness of fighting brain cancer. Compared to chemotherapy, the new drug and delivery method is more effective, increases the maximum dose that can be used, decreases toxicity and immunogenicity, and enhances the ability to target cancer cells specifically. Using the new delivery method allows anti-cancer agents to accumulate directly in solid tumors, which can aid in fighting multi-drug resistant cells.

Summary

  • The drug was engineered on a natural biodegradable nanoplatform.
  • The drug is specifically delivered to the tumor cells using a targeting monoclonal antibody.
  • This controllable unique drug releases tumor growth inhibiting agents specifically into cancer cells without affecting normal surrounding cells.
  • The active drug component blocks several cancer-specific tumor markers at the same time.
  • There is a significant survival increase in tumor-bearing animals (preclinical data) after the drug administration.
  • Using this technology, it is possible to block a combination of several unique markers for each individual patient at the same time, providing a synergistic effect.

Recent Publications

Lee BS, Fujita M, Khazenzon NM, Wawrowsky KA, Wachsmann-Hogiu S, Farkas DL, Black KL, Ljubimova JY, Holler E. (2006) Polycefin, a new prototype of a multifunctional nanoconjugate based on poly(β-L-malic acid) for drug delivery. Bioconjug. Chem. 17:317-326.

Ljubimova JY, Fujita M, Lee BS, Khazenzon NM, Wachsmann-Hogiu S, Farkas DL, Black KL, Holler E. (2006) Nanoconjugates of poly(malic acid) with functional modules for drug delivery. NSTI-Nanotech, 2:354-357.

Fujita M, Khazenzon NM, Ljubimov AV, Lee BS, Virtanen I, Holler E, Black KL, Ljubimova JY. (2006) Inhibition of laminin-8 in vivo using a novel poly(malic acid)-based carrier reduces glioma angiogenesis. Angiogenesis 9:183-191.

Ljubimova JY, Fujita M, Khazenzon NM, Lee BS, Wachsmann-Hogiu S, Farkas DL, BlackKL, Holler E. (2007) Nanoconjugate based on polymalic acid for tumor targeting. Chem. Biol. Interact. v.162, in press.

Fujita M, Lee B-S, Khazenzon NM, Wawrowsky KA, Penichet M, Patil R, Ding H, Holler E, Black KL, Ljubimova JY (2007) Direct brain tumor targeting using combination of monoclonal antibodies attached to biopoly(β-L-malic acid). J. Control. Release, 122:356-363.

Fujita M, Khazenzon NM, Lee B-S, Holler E, Black KL, Ljubimova JY. (2007) Development of Nanoconjugate with Different Monoclonal Antibodies to Inhibit Molecular Targets Important for Tumor Angiogenesis. Chapter 9: Cancer Diagnostics, Imaging & Treatment. NSTI-Nanotech, 2:760-762.

Ljubimova JY, Fujita M, Khazenzon NM, Lee BS, Wachsmann-Hogiu S, Farkas DL, Black KL, Holler E. Nanoconjugate based on polymalic acid for tumor targeting. Chem. Biol. Interact. v.171:195-203, 2008

Ljubimova JY, Fujita, M, Ljubimov, A.V., Torchilin V.P., Black K.L., Holler, E. Poly(malic acid) nanoconjugates containing various antibodies and oligonucleotides for multitargeting drug delivery, Nanomedicine 3:247-265, 2008

Ljubimova JY, Black KL, Ljubimov AV, Holler E. Biodegradable multitargeting nanoconjugates for drug delivery. In: Multifunctional Pharmaceutical Nanocarriers. Springer, pp. 233 - 262, 2008.





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