Functionalized Mesoporous Silica Nanoparticles for Tumor-Targeted and Controlled Drug Delivery
The engineering of multifunctional nanocarriers for targeted drug delivery shows promising potentials to revolutionize the cancer chemotherapy. Simple methods to optimize physicochemical characteristics and surface composition of the drug nanocarriers, such as size, geometry, selective targeting, and stability, need to be developed in order to tackle major challenges for smooth translation of suitable nanocarriers to clinical applications. In our study,[2,3] multifunctional mesoporous silica nanoparticles (MSNPs) were developed in order to deliver anticancer drugs to specific cancer cells in a targeted and controlled manner. The nanoparticle surface was functionalized with amino-β-cyclodextrin rings bridged by cleavable disulfide bonds, blocking drugs inside the mesopores of the nanoparticles. Poly(ethylene glycol) polymers, functionalized with adamantane unit at one end and folate unit at the other end, were immobilized onto the nanoparticle surface through strong β-cyclodextrin/adamantane complexation. We demonstrated that the high drug delivery efficacy of multifunctional nanoparticles is attributed to the cooperative effects of folate-mediated targeting and stimuli-triggered drug release provided by the nanoparticles. In another work,[4,5] poly(amidoamine) (PAMAM) dendrimers were modified onto the surface of MSNPs. A series of PAMAM-modified MSNPs were prepared and compared for their mucoadhesive capabilities on pig bladder wall and controlled drug release properties. The mucoadhesive capacity of PAMAM-modified MSNPs increased with increase in the number of PAMAM amino groups. An antineoplastic, doxorubicin, was encapsulated in the mesopores of the PAMAM-modified MSNPs and resulted in sustained release of the drug. The present study demonstrates that the mucoadhesive and drug release properties of MSNPs can be controlled by the layer number of PAMAM dendrimers on the nanoparticle surface, holding significant potential for the development of mucoadhesive drug delivery systems for bladder cancer therapy.