Increasing efforts are being put into the light-sensitive polymeric micelles that hold great potential for drug/gene/small interfering RNA delivery. However, these polymeric micelles lack highly efficient tumor-targeting properties and near-infrared light sensitivity, and often exhibit an uncontrollable drug-release profile. To address these problems, a new strategy is introduced that combines sugar-triggered targeting (active targeting) and two-photon sensitivity to afford a degradable and dendritic micellar nanocarrier, in which the desired sugar residues and light-responsive groups can be modularly conjugated and/or altered. A clinical anticancer drug, doxorubicin, can be released in a controlled manner by changing the light irradiation time, which is induced by the gradual disruption of micelles in aqueous solution. The glucose- and lactose-coated micelles further demonstrate specific binding with the lectins Concanavalin A and Ricinus communis agglutinin, respectively, which makes them useful as targeted drug-delivery vesicles.

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.

Copolymers of 2‐methylene‐1,3‐dioxepane (MDO) and methyl acrylate (MA) containing ester units both in the backbone and as pendant groups were synthesized by free‐radical copolymerization. The influence of reaction conditions such as the polymerization time, temperature, initiator concentration, and comonomer feed ratio on the yield, molecular weight, and copolymer composition was investigated. The structure of the copolymers was confirmed by 1H NMR, 13C NMR, and IR spectroscopy. Differential scanning calorimetry indicated that the copolymers had a random structure. An NMR study showed that hydrogen transfer occurred during the copolymerization. The reactivity ratios of the comonomers were rMDO = 0.0235 and rMA = 26.535. The enzymatic degradation of the copolymers obtained was carried out in the presence of proteinase K or a crude enzyme extracted from earthworms. The experimental results showed that the higher ester molar percentage in the backbone caused a faster degradation rate. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 2898–2904, 2003

Multi-armed biodegradable block copolymers with a bioreducible core mPCL-b-PEO were for the first time synthesized by thiol-yne click chemistry. They self-assembled into bioreducible micelles and hydrogels in aqueous solution, which demonstrated tunable size, mechanical and drug-release properties.

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Biocompatible and biodegradable ABC and ABCBA triblock and pentablock copolymers composed of poly(ε‐caprolactone) (PCL), poly(L‐lactide) (PLA), and poly(ethylene glycol) (PEO) with controlled molecular weights and low polydispersities were synthesized by a click conjugation between alkyne‐terminated PCL‐b‐PLA and azide‐terminated PEO. Their molecular structures, physicochemical and self‐assembly properties were thoroughly characterized by means of FT‐IR, 1H‐NMR, gel permeation chromatography, differential scanning calorimetry, wide‐angle X‐ray diffraction, dynamic light scattering, and transmission electron microscopy. These copolymers formed microphase‐separated crystalline materials in solid state, where the crystallization of PCL block was greatly restricted by both PEO and PLA blocks. These copolymers self‐assembled into starlike and flowerlike micelles with a spherical morphology, and the micelles were stable over 27 days in aqueous solution at 37 °C. The doxorubicin (DOX) drug‐loaded nanoparticles showed a bigger size with a similar spherical morphology compared to blank nanoparticles, demonstrating a biphasic drug‐release profile in buffer solution and at 37 °C. Moreover, the DOX‐loaded nanoparticles fabricated from the pentablock copolymer sustained a longer drug‐release period (25 days) at pH 7.4 than those of the triblock copolymer. The blank nanoparticles showed good cell viability, whereas the DOX‐loaded nanoparticles killed fewer cells than free DOX, suggesting a controlled drug‐release effect. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010

Both ultraviolet (UV) and near-infrared (NIR) light-responsive linear-dendritic amphiphiles, PEO-D3DNQ, were click conjugated by connecting the diazonaphthoquinone (DNQ)-decorated poly(amido amine) dendron D3 (generation 3) and linear poly(ethylene oxide) (PEO) with molecular weights of 2 or 5 kDa.They self-assembled into spherical micelles with a hydrophobic DNQ core stabilized by a hydrophilic PEO corona in aqueous solution. As characterized by time-resolved UV-vis spectroscopy, dynamic light scattering and TEM, these micelles showed both UV-and NIR-sensitivity in phosphate buffer solution.Under 365 nm UV irradiation, the characteristic absorption intensity of DNQ progressively decreased and then leveled off within 8 minutes, suggesting the completion of the Wolff rearrangement of DNQ, while it took a longer time of 40-60 minutes to complete the Wolff rearrangement of DNQ under 808 nm NIR irradiation. Most of the micelles were disrupted after 30 minutes of 808 nm irradiation, and the apparent drug-release rate of the doxorubicin (DOX)-loaded micelles showed a nearly 8-fold increase, presenting a NIR-triggered drug-release profile. The DOX-loaded micelles could quickly enter into HeLa cells, release DOX inside the cells, and then kill the cells in a NIR-triggered manner, as evidenced by flow cytometry, confocal laser scanning microscopy, and MTT assay.

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