title: In situ biodegradable crosslinking of cationic oligomer coating on mesoporous silica nanoparticles for drug delivery.
abstract: Although layer-by-layer assembly using anionic and cationic polymer has been a popular way to develop core-shell nanoparticles, the strong electrostatic interactions may limit shell degradability, thus hampering their application as a platform for controlled therapeutic delivery. In this study, we demonstrate a simple approach to developing mesoporous nanohybrids via a process of pre-drug loading (using doxorubicin (DOX) as a model drug) into mesoporous silica nanoparticles (MSN), followed by surface functionalization with a kind of cationic oligomer (low molecular weight polyethylene imine, LPEI) and in situ crosslinking by degradable N,N'-bis(acryloyl)cystamine (BAC). The presence of LPEI shell affords the nanohybrids with charge-reversal ability, which means that the acidic tumor extracellular microenvironment can transform the negative surface charge at neutral conditions into positive-charged ones. The nanohybrids displayed a pH- and redox-dual sensitivity in DOX release under conditions that mimic intracellular reductive conditions and acidic tumor microenvironments. The nanohybrids can be effectively internalized into A549 cells (a carcinomic human alveolar basal epithelial cell line), resulting in a high DOX intracellular accumulation and an improved anticancer cytotoxicity when compared with free DOX, suggesting their high potential as a new platform for therapeutic delivery.
authors.affiliation: The State Key Laboratory of Bioreactor Engineering and Key Laboratory for Ultrafine Materials of Ministry of Education, Key Laboratory for Ultrafine Materials of Ministry of Education, Engineering Research Centre for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Bioreactor Engineering and Key Laboratory for Ultrafine Materials of Ministry of Education, Key Laboratory for Ultrafine Materials of Ministry of Education, Engineering Research Centre for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Jine
authors.initials: J
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Bioreactor Engineering and Key Laboratory for Ultrafine Materials of Ministry of Education, Key Laboratory for Ultrafine Materials of Ministry of Education, Engineering Research Centre for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: The State Key Laboratory of Bioreactor Engineering and Key Laboratory for Ultrafine Materials of Ministry of Education, Key Laboratory for Ultrafine Materials of Ministry of Education, Engineering Research Centre for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.affiliation: The State Key Laboratory of Bioreactor Engineering and Key Laboratory for Ultrafine Materials of Ministry of Education, Key Laboratory for Ultrafine Materials of Ministry of Education, Engineering Research Centre for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: The State Key Laboratory of Bioreactor Engineering and Key Laboratory for Ultrafine Materials of Ministry of Education, Key Laboratory for Ultrafine Materials of Ministry of Education, Engineering Research Centre for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, China; Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Ministry of Education, College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, China. Electronic address: yulinli@ecust.edu.cn.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Bioreactor Engineering and Key Laboratory for Ultrafine Materials of Ministry of Education, Key Laboratory for Ultrafine Materials of Ministry of Education, Engineering Research Centre for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, China. Electronic address: liucs@ecust.edu.cn.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002412:Cations / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D002412:Cations; D020099:Coated Materials, Biocompatible; D003432:Cross-Linking Reagents; D012822:Silicon Dioxide; D004317:Doxorubicin
keywords: Anticancer drug delivery; Cationic oligomer assembly; Charge reversal; Mesoporous silica nanoparticles; pH/redox sensitivity