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Ligand Installation to Polymeric Micelles for Pediatric Brain Tumor Targeting
Takayoshi Watanabe1, Hayato Laurence Mizuno1,2, Jumpei Norimatsu1
1Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Abstract:
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.
Insights
Targeting medulloblastoma with nanocarriers improved drug delivery. Attaching anti-CD276 antibodies to nanocarriers enhanced cellular uptake in medulloblastoma cells, showing potential for better cancer treatment.
Area of Science:
- Oncology
- Nanotechnology
- Drug Delivery
Background:
- Medulloblastoma poses significant therapeutic challenges due to poor drug accumulation and limited cellular uptake.
- Enhancing drug internalization via ligand conjugation to tumor cells is a promising strategy.
- Nanocarriers offer improved drug loading and delivery versatility when combined with targeting ligands.
Purpose of the Study:
- To investigate the potential of targeting CD276/B7-H3 on medulloblastoma cells.
- To enhance cellular uptake of nanocarriers by installing anti-CD276 antibodies.
- To evaluate the efficacy of ligand-installed nanocarriers for medulloblastoma drug delivery.
Main Methods:
- Conjugation of anti-CD276 antibodies onto polyion complex micelles (PIC/m) using click chemistry.
- Utilizing CD276 as a target on medulloblastoma cells.
- Assessing cellular uptake efficiency of antibody-installed nanocarriers.
Main Results:
- Anti-CD276 antibody-installed PIC/m demonstrated enhanced intracellular delivery into CD276-expressing medulloblastoma cells.
- The enhanced delivery was confirmed to be CD276-dependent.
- Increased antibody density on nanocarrier surfaces correlated with improved cellular uptake efficiency.
Conclusions:
- Anti-CD276 antibody-installed nanocarriers show significant potential for improving drug delivery in medulloblastoma.
- Targeting CD276 represents a viable strategy for enhancing nanocarrier-mediated drug internalization.
- This approach may lead to more effective therapeutic outcomes for medulloblastoma patients.
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