NIR-Responsive and Lectin-Binding Doxorubicin-Loaded Nanomedicine from Janus-Type Dendritic PAMAM Amphiphiles

Abstract

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.

Dendrimers Terminated with Dichlorotriazine Groups Provide a Route to Compositional Diversity

“…Methods for characterizing such mixtures, however, are becoming increasingly refined. 3 Using convergent synthetic approaches, 4 dendrimers with specific compositional diversity can be obtained across a variety of platforms including aryl 5 and aliphatic 6 ethers, PAMAM 7 and triazines 8 by carrying the diversity-generating groups through the entire synthesis. Here, the synthetic burden is substantially increased and the versatility can be limited by the initial choice of the diversity elements.…”

“…Oftentimes, these products are blocks derived from the dimerization of a dendrons displaying two different surface chemistries 6a including those relying on selective click chemistry. 7 Recently, Rudick reported that a three-component Passerini coupling reaction has been efficiently utilized to generate triblock dendrimers of low generations from dendrons functionalized at the focus. 9 In contrast to convergent methods, divergent methods offer advantages in that they yield larger dendrimers, adding significant mass throughout the synthesis.…”

Intracellular Reduction‐Responsive Sheddable Copolymer Micelles for Targeted Anticancer Drug Delivery

“…As shown in Figure 7, HeLa cells were incubated with free DOX and DOX-loaded micelles for fixed time intervals of 15 min, 1 h, and 3 h. It was observed that free DOX entered into the cells in a time-dependent manner (Figure 7 a), suggesting that the uptake of free DOX by cancer cells is a diffusion process. [18] In comparison, the uptake of PCL-SS-POEGMA@FA/DOX micelles by cancer cells was realized through FA-receptor-mediated endocytosis, which improved the amount and rate of PCL-SS-PO-EGMA@FA/DOX internalization by HeLa cells (Figure 7 b). This result indicates that DOX-loaded micelles with sizes of < 100 nm and the FA targeting ligand facilitate their endocytosis by HeLa cells.…”

Engineered photo-responsive materials for near-infrared-triggered drug delivery

“…Especially, its photo-reaction can occur via one photon absorption of high-energy UV light and/or two-photon absorption of low-energy NIR light [25]. Therefore, DNQ-containing polymers have been widely utilized as a platform for the fabrication of NIR-responsive micellar drug carriers compared with the aforementioned azobenzene, spiropyran, and coumarin containing counterparts [34][35][36]. NIR-responsive micelles containing DNQ, chemo drugs, and photothermal agents is one example to demonstrate how the photo-active property of DNQ have been employed for targeted and spatiotemporal chemo-thermal therapy (Fig.…”

“…4) [35]. The dendritic polymer was synthesized by conjugating hydrophobic DNQ-decorated poly(amido amine) (PAMAM) dendron and hydrophilic lactose (Lac)-decorated PAMAM dendrons via click chemistry (Fig.…”