Hyaluronic acid ion-pairing nanoparticles for targeted tumor therapy

作者：Li, Wenhao; Yi, Xiaoli; Liu, Xing; Zhang, Zhirong; Fu, Yao^*; Gong, Tao^*

来源：Journal of Controlled Release, 2016, 225: 170-182.

DOI：10.1016/j.jconrel.2016.01.049

• Hyaluronic acid (HA)
• Doxorubicin (DOX)
• Nanoparticle
• Ion-pairing
• Liposome

Hyaluronic acid (HA)-based doxorubicin (DOX) nanoparticles (HA-NPs) were fabricated via ion-pairing between positively charged DOX and negatively charged HA, which displayed near-spherical shapes with an average size distribution of 180.2nm(PDI = 0.184). Next, HA-NPs were encapsulated in liposomal carriers to afford HA-based DOX liposomes (HA-LPs), which also showed near-spherical morphology with an average size of 130.5 nm (PDI = 0.201). HA-NPs and HA-LPs displayed desirable sustained-release profiles compared to free DOX, and moreover, HA-LPs were proven to prevent premature release of DOX from HA-NPs. Cell based studies demonstrated HA-NPs and HA-LPs were selectively taken up by CD44(+) tumor cells, and DOX was released intracellularly to target the cell nuclei. Both HA-NPs and HA-LPs showed comparable levels of penetration efficiency in tumor spheroids. In vivo studies revealed that HA-NPs and HA-LPs significantly prolonged the blood circulation time of DOX, decreased accumulation in the normal tissues and enriched drugs into the tumors. Furthermore, HA-NPs and HA-LPs greatly enhanced therapeutic efficacy of DOX in tumor-bearing mice and minimized systemic toxicity against vital organs. In sum, HA-NPs and HA-LPs represent promising nanocarriers for CD44(+) tumor-targeted delivery.

• 出版日期2016-3-10
• 单位四川大学