Riboflavin-containing telodendrimer nanocarriers for efficient doxorubicin delivery: High loading capacity, increased stability, and improved anticancer efficacy.
Riboflavin-containing telodendrimer nanocarriers for efficient doxorubicin delivery: High loading capacity, increased stability, and improved anticancer efficacy.
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DOI：
10.1016/j.biomaterials.2017.06.041
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发表时间：
2017-10
期刊：
影响因子：
14
通讯作者：
Luo J
中科院分区：
文献类型：
--
作者：
Guo D;Shi C;Wang X;Wang L;Zhang S;Luo J
我们已经开发了两个线性树枝状telodendrimers（TDs）的合理设计，使用两亲性核黄素（Rf）作为有效的阿霉素（DOX）交付的积木。胶束TD纳米颗粒（NP）由亲水性聚乙二醇（PEG）壳和用于DOX包封的含Rf的亲和核组成。由于DOX与Rf之间的强相互作用和两亲性Rf结构，这些纳米载体具有超高的DOX载药量（>1/1，DOX/TD，w/w）、~100%的载药效率、药物的持续释放和有效的肿瘤靶向药物递送的最佳粒径（20~40 nm）。这些纳米制剂显著延长了DOX在血液中的循环时间，而在多次注射后没有观察到加速清除。DOX-TD在体内有效靶向几种类型的肿瘤，例如Raji淋巴瘤、MDA-MB-231乳腺癌和SKOV 3卵巢癌。相对于游离DOX和Doxil®，纳米制剂在小鼠中DOX的体内最大耐受剂量（MTD）增加2~2.5倍。这些纳米制剂显著抑制肿瘤生长并延长携带SKOV 3卵巢癌异种移植物的小鼠的存活。综上所述，含Rf的纳米制剂具有高DOX负载能力、改善的稳定性和有效的肿瘤靶向，导致上级抗肿瘤功效，值得进一步开发用于临床应用。
We have developed two linear-dendritic telodendrimers (TDs) with rational design using amphiphilic riboflavin (Rf) as building blocks for efficient doxorubicin (DOX) delivery. Micellar TD nanoparticles (NPs) are composed of a hydrophilic polyethylene glycol (PEG) shell and a Rf-containing affinitive core for DOX encapsulation. Strong DOX-Rf interactions and amphiphilic Rf structure render these nanocarriers with an ultra-high DOX loading capacity (>1/1, DOX/TD, w/w), ~100% loading efficiency, the sustained drug release and the optimal particle sizes (20~40 nm) for efficient tumor-targeted drug delivery. These nanoformulations significantly prolonged DOX circulation time in the blood without the accelerated clearance observed after multiple injections. DOX-TDs target several types of tumors efficiently in vivo, e.g. Raji lymphoma, MDA-MB-231 breast cancer, and SKOV3 ovarian cancer. In vivo maximum tolerated dose (MTD) of DOX was increased by 2~2.5 folds for the nanoformulations in mice relative to those of free DOX and Doxil®. These nanoformulations significantly inhibited tumor growth and prolonged survival of mice bearing SKOV3 ovarian cancer xenografts. In summary, Rf-containing nanoformulations with high DOX loading capacity, improved stability and efficient tumor targeting lead to superior antitumor efficacy, which merit the further development for clinical application.
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影响因子：
14
作者：
He, Zhijian;Wan, Xiaomeng;Schulz, Anita;Bludau, Herdis;Dobrovolskaia, Marina A.;Stern, Stephan T.;Montgomery, Stephanie A.;Yuan, Hong;Li, Zibo;Alakhova, Dania;Sokolsky, Marina;Darr, David B.;Perou, Charles M.;Jordan, Rainer;Luxenhofer, Robert;Kabanov, Alexander V.
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4.8
作者：
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通讯作者：
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影响因子：
45.3
作者：
DANA, BW;DAHLBERG, S;FISHER, RI
通讯作者：
FISHER, RI
影响因子：
38.3
作者：
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