Department of Polymer Science and Engineering, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
Biomacromolecules. 2012 Nov 12;13(11):3581-91. doi: 10.1021/bm3010325. Epub 2012 Oct 9.
Janus-type dendritic poly(amido amine) (PAMAM) amphiphiles Dm-Lac-D3DNQ were synthesized by connecting hydrophobic diazonaphthoquinone (DNQ)-decorated PAMAM dendron D3 (generation 3) and hydrophilic lactose (Lac)-decorated PAMAM dendrons Dm (generations 0-2, m = 0-2) via click chemistry. They self-assembled into the DNQ-cored micelles dangled by densely free Lac groups in aqueous solution. Irradiated by 808 nm laser and 365 nm lamp, both NIR- and UV-sensitivity of micelles were characterized by time-resolved UV-vis spectroscopy. The characteristic absorption intensity of DNQ progressively decreased and then leveled off. Moreover, the bigger the micelles, the more the irradiation time for finishing Wolff rearrangement of DNQ. TEM further confirmed that most of the micelles disassembled after 30 min of 808 nm laser irradiation. The Lac-coated micelles showed binding with RCA(120) lectin, as monitored by UV-vis and DLS. The apparent drug-release rate of doxorubicin (DOX) loaded nanomedicine nearly doubled after 10 min of 808 nm laser irradiation, presenting a NIR-triggered drug-release profile. Moreover, the DOX-loaded nanomedicine presented a phototriggered cytotoxicity that was close to free DOX, and they could quickly enter into HeLa cells, as evidenced by MTT assay, flow cytometry, and CLSM. Importantly, this work provides a versatile strategy for the fabrication of NIR-responsive and lectin-binding dendrimer nanomedicine, opening a new avenue for "on-demand" and spatiotemporal drug delivery.
Janus 型树枝状聚酰胺-胺（PAMAM）两亲体 Dm-Lac-D3DNQ 是通过连接疏水性重氮萘醌（DNQ）修饰的 PAMAM 树枝状大分子 D3（第 3 代）和亲水性乳糖（Lac）修饰的 PAMAM 树枝状大分子 Dm（第 0-2 代，m=0-2）通过点击化学合成的。它们在水溶液中自组装成 DNQ 核的胶束，胶束上悬挂着密集的自由 Lac 基团。用 808nm 激光和 365nm 灯照射，通过时间分辨紫外可见光谱研究了胶束的近红外和紫外敏感性。DNQ 的特征吸收强度逐渐降低，然后趋于稳定。此外，胶束越大，完成 DNQ 的 Wolff 重排所需的辐照时间就越长。TEM 进一步证实，大多数胶束在 808nm 激光照射 30 分钟后解体。用紫外可见光谱和 DLS 监测到，涂有乳糖的胶束与 RCA(120)凝集素结合。负载阿霉素（DOX）的纳米药物的表观药物释放率在 808nm 激光照射 10 分钟后几乎增加了一倍，呈现出近红外触发的药物释放特性。此外，负载 DOX 的纳米药物表现出与游离 DOX 接近的光触发细胞毒性，MTT 测定、流式细胞术和 CLSM 证明它们可以快速进入 HeLa 细胞。重要的是，这项工作为制备近红外响应和凝集素结合的树枝状纳米药物提供了一种通用策略，为“按需”和时空药物输送开辟了新途径。
