Hyaluronic acid ion-pairing nanoparticles for targeted tumor therapy

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• 作者：Wenhao Li ; Xiaoli Yi ; Xing Liu ; Zhirong Zhang ; Yao Fu ; ^{yfu4@scu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Tao Gong ; ^{gongtaoy@126.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Hyaluronic acid (HA) ; Doxorubicin (DOX) ; Nanoparticle ; Ion-pairing ; Liposome
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：10 March 2016
• 年：2016
• 卷：225
• 期：Complete
• 页码：170-182
• 全文大小：2312 K

文摘

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 180.2 nm (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.