Ligand Installation to Polymeric Micelles for Pediatric Brain Tumor Targeting.

Autor: Watanabe T; Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan., Mizuno HL; Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.; Department of Biochemistry and Cellular Biology, National Center of Neurology and Psychiatry (NCNP), Tokyo 187-8551, Japan., Norimatsu J; Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan., Obara T; Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan., Cabral H; Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan., Tsumoto K; Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.; Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Tokyo 113-8654, Japan.; Medical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo, Tokyo 113-8654, Japan., Nakakido M; Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.; Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Tokyo 113-8654, Japan., Kawauchi D; Department of Biochemistry and Cellular Biology, National Center of Neurology and Psychiatry (NCNP), Tokyo 187-8551, Japan., Anraku Y; Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.; Department of Materials Science and Engineering, School of Materials and Chemical Technology, Tokyo Institute of Technology, Tokyo 152-8550, Japan.
Jazyk: angličtina
Zdroj: Polymers [Polymers (Basel)] 2023 Apr 06; Vol. 15 (7). Date of Electronic Publication: 2023 Apr 06.
DOI: 10.3390/polym15071808
Abstrakt: Medulloblastoma is a life-threatening disease with poor therapeutic outcomes. In chemotherapy, low drug accumulation has been a cause of these outcomes. Such inadequate response to treatments has been associated with low drug accumulation, particularly with a limited cellular uptake of drugs. Recently, the conjugation of drugs to ligand molecules with high affinity to tumor cells has attracted much attention for enhancing drug internalization into target cells. Moreover, combining tumor-targeting ligands with nano-scaled drug carriers can potentially improve drug loading capacity and the versatility of the delivery. Herein, we focused on the possibility of targeting CD276/B7-H3, which is highly expressed on the medulloblastoma cell membrane, as a strategy for enhancing the cellular uptake of ligand-installed nanocarriers. Thus, anti-CD276 antibodies were conjugated on the surface of model nanocarriers based on polyion complex micelles (PIC/m) via click chemistry. The results showed that the anti-CD276 antibody-installed PIC/m improved intracellular delivery into CD276-expressing medulloblastoma cells in a CD276-dependent manner. Moreover, increasing the number of antibodies on the surface of micelles improved the cellular uptake efficiency. These observations indicate the potential of anti-CD276 antibody-installed nanocarriers for promoting drug delivery in medulloblastoma.
Databáze: MEDLINE
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