Highly Efficient siRNA Delivery from Core-Shell Mesoporous Silica Nanoparticles with Multifunctional Polymer Caps
A new general route for siRNA delivery is presented combining porous core-shell silica nanocarriers with a modularly designed multifunctional block copolymer. Specifically, the internal storage and release of siRNA from mesoporous silica nanoparticles (MSN) with orthogonal core-shell surface chemistry was investigated as a function of pore-size, pore morphology, surface properties and pH. Very high siRNA loading capacities of up to 380 microg/mg MSN were obtained with charge-matched amino-functionalized mesoporous cores, and release profiles show up to 80% siRNA elution after 24 h. We demonstrate that adsorption and desorption of siRNA is mainly driven by electrostatic interactions, which allow for high loading capacities even in medium-sized mesopores with pore diameters down to 4 nm in a stellate pore morphology. The negatively charged MSN shell enabled the association with a block copolymer containing positively charged artificial amino acids and oleic acid blocks, which acts simultaneously as capping function and endosomal release agent. The potential of this multifunctional delivery platform is demonstrated by highly effective cell transfection and siRNA delivery into KB-cells. A luciferase reporter gene knock-down of up to 90% was possible using extremely low cell exposures with only 2.5 microg MSN containing 32 pM siRNA per 100 microL well.
Code (0)
등록된 구현이 없습니다.
Similar Papers 제목 키워드 기반
Mesoporous core-shell silica nanoparticles with anti-fouling properties for ovarian cancer therapy
Mesoporous silica nanoparticles (MSNPs) have many potential applications in biomedical fields. However, when MSNPs are exposed to plasma, protein adsorption leads to opsonization and decreases blood circulation time. A n…
Mesoporous silica nanoparticles containing silver as novel antimycobacterial agents against Mycobacterium tuberculosis
Tuberculosis remains today a major public health issue with a total of 9 million new cases and 2 million deaths annually. The lack of an effective vaccine and the increasing emergence of new strains of Mycobacterium tube…
Targeted nanoconjugate co-delivering siRNA and tyrosine kinase inhibitor to KRAS mutant NSCLC dissociates GAB1-SHP2 post oncogene knockdown
A tri-block nanoparticle (TBN) comprising of an enzymatically cleavable porous gelatin nanocore encapsulated with gefitinib (tyrosine kinase inhibitor (TKI)) and surface functionalized with cetuximab-siRNA conjugate has …
Response of RAW 264.7 and J774A.1 macrophages to particles and nanoparticles of a mesoporous bioactive glass: A comparative study"
Mesoporous bioactive glasses (MBGs) are bioceramics designed to induce bone tissue regeneration and very useful materials with the ability to act as drug delivery systems. MBGs can be implanted in contact with bone tissu…
Effective reduction of biofilm through photothermal therapy by gold core@shell based mesoporous silica nanoparticles
Bacterial biofilms can initiate chronic infections that become difficult to eradicate. There is an unmet need for effective therapeutic strategies that control and inhibit the growth of these biofilms. Herein, light sens…