1. Lactoferrin/CD133 antibody conjugated nanostructured lipid carriers for dual targeting of blood-brain-barrier and glioblastoma stem cells.
- Author
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Zhao C, Zhu X, Yang H, Tan J, Gong R, Mei C, Cai X, Su Z, and Kong F
- Subjects
- Humans, Cell Line, Tumor, Animals, Mice, Drug Delivery Systems, Antibodies chemistry, Blood-Brain Barrier metabolism, Glioblastoma drug therapy, Glioblastoma metabolism, Glioblastoma pathology, Lactoferrin chemistry, AC133 Antigen metabolism, Neoplastic Stem Cells drug effects, Neoplastic Stem Cells metabolism, Temozolomide pharmacology, Nanostructures chemistry, Drug Carriers chemistry, Lipids chemistry, Brain Neoplasms drug therapy, Brain Neoplasms metabolism, Brain Neoplasms pathology
- Abstract
The main reasons for the difficulty in curing and high recurrence rate of glioblastoma multiforme (GBM) include: 1. The difficulty of chemotherapy drugs in penetrating the blood-brain barrier (BBB) to target tumor cells; 2. The presence of glioma stem cells (GSCs) leading to chemotherapy resistance. Therefore, breaking through the limitations of the BBB and overcoming the drug resistance caused by GSCs are the main strategies to address this problem. This study presents our results on the development of lactoferrin (Lf)/CD133 antibody conjugated nanostructured lipid carriers (Lf/CD133-NLCS) for simultaneously targeting BBB and GSCs. Temozolomide (TMZ) loaded Lf/CD133-NLCS (Lf/CD133-NLCS-TMZ) exhibited high-efficiency in vitro anti-tumor effects toward malignant glioma cells (U87-MG) and GSCs, while demonstrating no significant toxicity to normal cells at concentrations lower than 200 μg ml
-1 . The results of the in vitro targeting GBM study revealed a notably higher cellular uptake of Lf/CD133-NLCS-TMZ in U87-MG cells and GSCs in comparison to Lf/CD133 unconjugated counterpart (NLCS-TMZ). In addition, increased BBB permeability were confirmed for Lf/CD133-NLCS-TMZ compared to NLCS-TMZ both in vitro and in vivo . Taking together, Lf/CD133-NLCS-TMZ show great potential for dual targeting of BBB and GSCs, as well as GBM therapy based on this strategy., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)- Published
- 2024
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