Target delivering paclitaxel by ferritin heavy chain nanocages for glioma treatment

Published on Jul 10, 2020in Journal of Controlled Release9.776
· DOI :10.1016/J.JCONREL.2019.12.010
Lin Li5
Estimated H-index: 5
(Sichuan University)
Sources
Abstract
Abstract Glioma is one of the most common aggressive brain malignancies, but the treatment of glioma is still far from satisfying. The efficiency of chemotherapy – the major choice of glioma treatment – is severely limited by low chemotherapeutic agents delivery across blood-brain barrier (BBB) and low tumor retention. Therefore, a safe and effective drug delivery system to help chemotherapy agents traverse the BBB and accumulate at tumor sites is urgently needed. Paclitaxel (PTX) is one of the most common and effective chemotherapy agent, however, it suffers from extremely low solubility and BBB penetration ability. Herein, we developed endogenous human ferritin heavy chain nanocage (HFn) as PTX carrier, which could specifically bind to widely overexpressed transferrin receptor 1 (TfR1) on BBB and glioma cells. We propose that this binding may help PTX cross the BBB and enhance its tumor accumulation. PTX-loaded HFn (HFn-PTX) was prepared and exhibited satisfactory targeting effect in Bend.3 and C6 cells in vitro. In vivo tissue biodistribution assay also demonstrated that HFn-PTX could indeed promote the accumulation of PTX in the brain. HFn-PTX exhibited the best anti-tumor effect with median survival time of 30 days, significantly longer than that of free PTX (14 days) and physiological saline group (13 days). In summary, we have designed and fabricated an effective delivery system for PTX to treat glioma. We also provided evidences that Transferrin (Tf) could not prevent the binding of HFn to TfR1 nor consequent TfR1-mediated HFn uptake, providing a clue for future research.
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