Alginate-based cancer-associated, stimuli-driven and turn-on theranostic prodrug nanogel for cancer detection and treatment.

Alginate-based cancer-associated, stimuli-driven and turn-on theranostic prodrug nanogels were designed for the tumor diagnosis and chemotherapy, by crosslinking the folate-terminated poly(ethylene glycol) (FA-PEG-NH2) and rhodamine B (RhB)-terminated poly(ethylene glycol) (RhB-PEG-NH2) modified oxidized alginate (OAL-g-PEG-FA/RhB) with cystamine (Cys), followed covalent conjugation of doxorubicin (DOX) via acid-labile Schiff base bond. Owing to the surface folic acid (FA) groups, disulfide crosslinking structure and Schiff base conjugation for DOX, the folate receptor (FR)-mediated targeting and pH/reduction dual responsive intracellular triggered release of DOX was achieved. The cytotoxicity and cellular uptake results clearly illustrated that most DOX was released and accumulated in the cell nuclei and killed the cancer cells efficaciously, due to the desirable targeting intracellular triggered release. Furthermore, the theranostic nanogels could be used for the real-time and noninvasive location tracking to cancer cells, owing to the pH-modulated fluorescence property of the pendant RhB groups.

[1]  P. Liu,et al.  Biocompatible graphene oxide nanoparticle-based drug delivery platform for tumor microenvironment-responsive triggered release of doxorubicin. , 2014, Langmuir : the ACS journal of surfaces and colloids.

[2]  Zhijun Zhang,et al.  Cancer-Targeted Nanotheranostics: Recent Advances and Perspectives. , 2016, Small.

[3]  P. Liu,et al.  PEGylated Oxidized Alginate-DOX Prodrug Conjugate Nanoparticles Cross-Linked with Fluorescent Carbon Dots for Tumor Theranostics. , 2016, ACS biomaterials science & engineering.

[4]  David J Mooney,et al.  Controlling alginate gel degradation utilizing partial oxidation and bimodal molecular weight distribution. , 2005, Biomaterials.

[5]  Peng Liu,et al.  Facile preparation of pH/reduction dual-responsive prodrug microspheres with high drug content for tumor intracellular triggered release of DOX , 2017 .

[6]  Wen He,et al.  Research progress on chemical modification of alginate: A review , 2011 .

[7]  P. Liu,et al.  Multi-functionalized hyaluronic acid nanogels crosslinked with carbon dots as dual receptor-mediated targeting tumor theranostics. , 2016, Carbohydrate polymers.

[8]  J. H. Park,et al.  Polysaccharide-based nanoparticles for theranostic nanomedicine. , 2016, Advanced drug delivery reviews.

[9]  Y. Omidi,et al.  Folate-conjugated thermosensitive O-maleoyl modified chitosan micellar nanoparticles for targeted delivery of erlotinib. , 2017, Carbohydrate polymers.

[10]  S. Nair,et al.  Smart stimuli sensitive nanogels in cancer drug delivery and imaging: a review. , 2013, Current pharmaceutical design.

[11]  D. Mooney,et al.  Alginate: properties and biomedical applications. , 2012, Progress in polymer science.

[12]  Ren-Shen Lee,et al.  Synthesis and characterization of amphiphilic photocleavable polymers based on dextran and substituted-ɛ-caprolactone. , 2015, Carbohydrate polymers.

[13]  Man Xiao,et al.  pH-Sensitive drug delivery system based on hydrophobic modified konjac glucomannan. , 2017, Carbohydrate polymers.

[14]  Hyun-Jong Cho,et al.  Polyethylene glycol-conjugated chondroitin sulfate A derivative nanoparticles for tumor-targeted delivery of anticancer drugs. , 2016, Carbohydrate polymers.

[15]  Kevin J Edgar,et al.  Alginate derivatization: a review of chemistry, properties and applications. , 2012, Biomaterials.

[16]  P. Liu,et al.  Novel fluorescent pH/reduction dual stimuli-responsive polymeric nanoparticles for intracellular triggered anticancer drug release , 2016 .

[17]  Juyoung Yoon,et al.  Cancer‐Associated, Stimuli‐Driven, Turn on Theranostics for Multimodality Imaging and Therapy , 2017, Advanced materials.

[18]  F. Veronese,et al.  Antitumoral activity of PEG-gemcitabine prodrugs targeted by folic acid. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[19]  K. Hidajat,et al.  β-Cyclodextrin conjugated magnetic, fluorescent silica core-shell nanoparticles for biomedical applications. , 2013, Carbohydrate polymers.

[20]  F. Štěpánek,et al.  Gadolinium alginate nanogels for theranostic applications. , 2017, Colloids and surfaces. B, Biointerfaces.

[21]  Jin Zeng,et al.  Double-Cross-Linked Hyaluronic Acid Nanoparticles with pH/Reduction Dual-Responsive Triggered Release and pH-Modulated Fluorescence for Folate-Receptor-Mediated Targeting Visualized Chemotherapy. , 2016, Biomacromolecules.

[22]  V. Atkin,et al.  Silver Alginate Hydrogel Micro- and Nanocontainers for Theranostics: Synthesis, Encapsulation, Remote Release, and Detection. , 2017, ACS applied materials & interfaces.

[23]  P. Sriamornsak,et al.  Thiolated pectin-doxorubicin conjugates: Synthesis, characterization and anticancer activity studies. , 2017, Carbohydrate polymers.

[24]  Yanxi Zhang,et al.  Reversible three-state switching of multicolor fluorescence emission by multiple stimuli modulated FRET processes within thermoresponsive polymeric micelles. , 2010, Angewandte Chemie.

[25]  B. Mu,et al.  Disintegration-controllable stimuli-responsive polyelectrolyte multilayer microcapsules via covalent layer-by-layer assembly. , 2011, Colloids and surfaces. B, Biointerfaces.

[26]  João Rodrigues,et al.  Biodegradable Polymer Nanogels for Drug/Nucleic Acid Delivery. , 2015, Chemical reviews.

[27]  F. Cheng,et al.  In vitro and in vivo applications of alginate/iron oxide nanocomposites for theranostic molecular imaging in a brain tumor model , 2015 .