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Derivatization of Hyaluronan to Target Neuroblastoma and Neuroglioma Expressing CD44
Giau Van Vo1,2, Kummara Madhusudana Rao3,4, Ildoo Chung4
1Department of Bionano Technology, Gachon Bionano Research Institute, Gachon University, 1342 Seongnam-daero, Sujeong-gu, Seongnam-si 13120, Gyeonggi-do, Republic of Korea.
Abstract:
Therapeutics for actively targeting over-expressed receptors are of great interest because the majority of diseased tissues originate from normal cells and do not possess a unique receptor from which they can be differentiated. One such receptor is CD44, which has been shown to be highly overexpressed in many breast cancers and other types of cancer cells. While CD44 has been documented to express low levels in normal adult neurons, astrocytes, and microglia, this receptor may be overexpressed by neuroblastoma and neuroglioma. If differential expression exists between normal and cancerous cells, hyaluronan (HA) could be a useful carrier that targets carcinomas. Thus, HA was conjugated with resveratrol (HA-R), and its efficacy was tested on cortical-neuroblastoma hybrid, neuroblastoma, and neuroglioma cells. Confocal and flow cytometry showed these cells express CD44 and are able to bind and uptake HA-R. The toxicity of HA-R correlated well with CD44 expression in this study. Therefore, conjugating resveratrol and other chemotherapeutics to HA could minimize the side effects for normal cells within the brain and nervous system and could be a viable strategy for developing targeted therapies.
Insights
Hyaluronan (HA) conjugated with resveratrol (HA-R) effectively targeted CD44-overexpressing neuroblastoma and neuroglioma cells. This targeted drug delivery approach shows promise for minimizing side effects in brain cancer therapies.
Area of Science:
- Oncology
- Nanomedicine
- Neuroscience
Background:
- Targeted therapeutics are crucial as many diseases arise from normal cells lacking unique receptors.
- CD44 receptor is overexpressed in various cancers, including breast cancer, and potentially in neuroblastoma and neuroglioma.
- Low CD44 expression in normal neurons, astrocytes, and microglia suggests potential for selective targeting.
Purpose of the Study:
- To investigate hyaluronan (HA) as a carrier for targeted drug delivery in CD44-overexpressing brain tumors.
- To evaluate the efficacy and toxicity of HA conjugated with resveratrol (HA-R) in neuroblastoma and neuroglioma models.
Main Methods:
- Conjugation of hyaluronan with resveratrol (HA-R).
- Testing HA-R efficacy on cortical-neuroblastoma hybrid, neuroblastoma, and neuroglioma cell lines.
- Utilizing confocal microscopy and flow cytometry to assess CD44 expression, HA-R binding, and cellular uptake.
Main Results:
- Confirmed CD44 expression on tested neuroblastoma and neuroglioma cells.
- Demonstrated successful binding and uptake of HA-R by these CD44-expressing cells.
- Observed toxicity of HA-R correlated with CD44 expression levels.
Conclusions:
- Hyaluronan-resveratrol conjugate (HA-R) is a viable targeted therapeutic strategy for CD44-overexpressing brain tumors.
- Targeting CD44 with HA-drug conjugates can potentially minimize side effects on normal neural cells.
- This approach offers a promising avenue for developing safer and more effective cancer therapies in the central nervous system.
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