title: Dendrimer-assisted formation of fluorescent nanogels for drug delivery and intracellular imaging.
abstract: Although, in general, nanogels present a good biocompatibility and are able to mimic biological tissues, their unstability and uncontrollable release properties still limit their biomedical applications. In this study, a simple approach was used to develop dual-cross-linked dendrimer/alginate nanogels (AG/G5), using CaCl2 as cross-linker and amine-terminated generation 5 dendrimer (G5) as a cocrosslinker, through an emulsion method. Via their strong electrostatic interactions with anionic AG, together with cross-linker Ca(2+), G5 dendrimers can be used to mediate the formation of more compact structural nanogels with smaller size (433 ± 17 nm) than that (873 ± 116 nm) of the Ca(2+)-cross-linked AG nanogels in the absence of G5. Under physiological (pH 7.4) and acidic (pH 5.5) conditions, the sizes of Ca(2+)-cross-linked AG nanogels gradually decrease probably because of their degradation, while dual-cross-linked AG/G5 nanogels maintain a relatively more stable structure. Furthermore, the AG/G5 nanogels effectively encapsulate the anticancer drug doxorubicin (Dox) with a loading capacity 3 times higher than that of AG nanogels. The AG/G5 nanogels were able to release Dox in a sustained way, avoiding the burst release observed for AG nanogels. In vitro studies show that the AG/G5-Dox NGs were effectively taken up by CAL-72 cells (a human osteosarcoma cell line) and maintain the anticancer cytotoxicity levels of free Dox. Interestingly, G5 labeled with a fluorescent marker can be integrated into the nanogels and be used to track the nanogels inside cells by fluorescence microscopy. These findings demonstrate that AG/G5 nanogels may serve as a general platform for therapeutic delivery and/or cell imaging.
authors.affiliation: CQM - Centro de Química da Madeira, MMRG, Universidade da Madeira , Campus Universitário da Penteada, 9020-105 Funchal, Portugal.
authors.forename: Mara
authors.initials: M
authors.lastname: Gonçalves
authors.forename: Dina
authors.initials: D
authors.lastname: Maciel
authors.forename: Débora
authors.initials: D
authors.lastname: Capelo
authors.forename: Shili
authors.initials: S
authors.lastname: Xiao
authors.forename: Wenjie
authors.initials: W
authors.lastname: Sun
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Shi
authors.forename: João
authors.initials: J
authors.lastname: Rodrigues
authors.forename: Helena
authors.initials: H
authors.lastname: Tomás
authors.forename: Yulin
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D005453:Fluorescence; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D000080385:Nanogels; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D050091:Dendrimers; D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D004317:Doxorubicin; D011094:Polyethyleneimine