Synthesis and Characterization of Thermally Responsive Pluronic F127−Chitosan Nanocapsules for Controlled Release and Intracellular Delivery of Small Molecules

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• 作者：Wujie Zhang ; Kyle Gilstrap ; Laying Wu ; Remant Bahadur K. C. ; Melissa A. Moss ; Qian Wang ; Xiongbin Lu ; Xiaoming He
• 刊名：ACS Nano
• 出版年：2010
• 出版时间：November 23, 2010
• 年：2010
• 卷：4
• 期：11
• 页码：6747-6759
• 全文大小：619K
• 年卷期：0
• ISSN：1936-086X

文摘

In this study, we synthesized empty core−shell structured nanocapsules of Pluronic F127 and chitosan and characterized the thermal responsiveness of the nanocapsules in size and wall-permeability. Moreover, we determined the feasibility of using the nanocapsules to encapsulate small molecules for temperature-controlled release and intracellular delivery. The nanocapsules are ∼37 nm at 37 °C and expand to ∼240 nm when cooled to 4 °C in aqueous solutions, exhibiting >200 times change in volume. Moreover, the permeability of the nanocapsule wall is high at 4 °C (when the nanocapsules are swollen), allowing free diffusion of small molecules (ethidium bromide, MW = 394.3 Da) across the wall, while at 37 °C (when the nanocapsules are swollen), the wall-permeability is so low that the small molecules can be effectively withheld in the nanocapsule for hours. As a result of their thermal responsiveness in size and wall-permeability, the nanocapsules are capable of encapsulating the small molecules for temperature-controlled release and intracellular delivery into the cytosol of both cancerous (MCF-7) and noncancerous (C3H10T1/2) mammalian cells. The cancerous cells were found to take up the nanocapsules much faster than the noncancerous cells during 45 min incubation at 37 °C. Moreover, toxicity of the nanocapsules as a delivery vehicle was found to be negligible. The Pluronic F127−chitosan nanocapsules should be very useful for encapsulating small therapeutic agents to treat diseases particularly when it is combined with cryotherapy where the process of cooling and heating between 37 °C and hypothermic temperatures is naturally done.