title: 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.
authors.affiliation: Department of Polymer Science and Engineering, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Ma
authors.forename: Chang-Ming
authors.initials: CM
authors.lastname: Dong
authors.forename: Bangshang
authors.initials: B
authors.lastname: Zhu
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Zhu
mesh_terms: D045744:Cell Line, Tumor; D050091:Dendrimers; D003979:Diazonium Compounds / Q000737:chemistry; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems; D006367:HeLa Cells; D006801:Humans; D037102:Lectins / Q000737:chemistry / Q000378:metabolism; D008823:Micelles; D050997:Nanomedicine; D011073:Polyamines / Q000737:chemistry; D014466:Ultraviolet Rays
chemical_list: D050091:Dendrimers; D003979:Diazonium Compounds; D037102:Lectins; D008823:Micelles; C531249:Poly(amidoamine); D011073:Polyamines; D004317:Doxorubicin