Liposomal Carrier Conjugated to APP-Derived Peptide for Brain Cancer Treatment

Martin Gabay, Abraham Weizman, Nidal Zeineh, Meygal Kahana, Fadi Obeid, Nahum Allon, Moshe Gavish

Research output: Contribution to journalArticlepeer-review

Abstract

Brain tumors are hard to treat with the currently available therapy. The major obstacle in the treatment of brain tumors is the lack of therapeutic strategies capable to penetrate the blood–brain barrier (BBB). The BBB is an endothelial interface that separates the brain from the circulatory blood system and prevents the exposure of the central nervous system (CNS) to circulating toxins and potentially harmful compounds. Unfortunately, the BBB prevents also the penetration of therapeutic compounds into the brain. We present here a drug-delivery liposomal carrier, conjugated to a peptide inserted in the liposomal membrane, which is putatively recognized by BBB transporters. The peptide is a short sequence of 5 amino acids (RERMS) present in the amyloid precursor protein (APP). This APP-targeted liposomal system was designed specifically for transporting compounds with anti-cancer activity via the BBB into the brain in an effective manner. This drug-delivery liposomal carrier loaded with the anti-cancer compounds temozolomide (TMZ), curcumin, and doxorubicin crossed the BBB in an in vitro model as well as in vivo (mice model). In the in vitro model, the targeted liposomes crossed the BBB model fourfold higher than the non-targeted liposomes. Labeled targeted liposomes penetrated the brain in vivo 35% more than non-targeted liposomes. Treatment of mice that underwent intracranial injection of human U87 glioblastoma, with the targeted liposomes loaded with the three tested anti-cancer agents, delayed the tumor growth and prolonged the mice survival in a range of 45% -70%. It appears that the targeted liposomal drug-delivery system enables better therapeutic efficacy in a SCID mouse model of glioblastoma compared to the corresponding non-targeted liposomes and the free compounds.

Original languageEnglish
Pages (from-to)1019-1029
Number of pages11
JournalCellular and Molecular Neurobiology
Volume41
Issue number5
DOIs
StatePublished - Jul 2021

Keywords

  • APP-targeted liposomes
  • Blood–brain barrier (BBB)
  • Curcumin
  • Doxorubicin
  • Glioblastoma
  • Temozolomide (TMZ)

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