Cedars-Sinai Medical Center

Alexander Ljubimov

Keith L Black

Julia Y Ljubimova

Eggehard Holler

Nanoconjugates that include a polymalic-based molecular scaffold with one or more imaging moiety and one or more targeting modules attached to the scaffold are provided. Methods of targeting a diseased cell or a diseased tissue in a subject by administering the nanoconjugate are described. Methods of synthesizing the nanoconjugate are also provided.

Polymalic acid based nanoconjugates for imaging

Using gene array technology, we observed that an increase of the &#x3b1;4 chain-containing Laminin-8 correlated with poor prognosis for patients with brain gliomas. We established that inhibition of Laminin-8 expression by a new generation of highly specific and stable antisense oligonucleotides (Morpholino&#x2122;) against chains of Laminin-8 could slow or stop the spread of glioma. This was demonstrated in an in vitro model using human glioblastoma multiforme cell lines M059K and U-87MG co-cultured with normal human brain microvascular endothelial cells (HBMVEC). Using Western blot analysis and immunohistochemistry, we con-firmed that antisense treatment effectively blocked laminin-8 protein synthesis. Antisense oligonucleotides against both &#x3b1;4 and &#x3b2;1 chains of laminin-8 blocked significantly the invasion of co-cultures through Matrigel. The results show that Laminin-8 may not only contribute to glioma progression and recurrence as part of the neovascularization process but also by directly increasing the invasive potential of tumor cells.

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Studio City, CA, United States of America

Alexander Ljubimov