Smart Delivery Project

Combination drug therapy, a regimen in which multiple drugs with different therapeutic outcomes are used in parallel or in sequence, has become one of the dominant strategies in the clinical treatment of cancer. Unlike monotherapy, combination therapy maximizes therapeutic efficacy against individual targets and is more likely to overcome drug resistance while also increasing the odds of a positive prognosis and reducing harmful side effects. The development of nanotechnologies for effective delivery of multiple drugs candidates in a temporally regulated manner to cancer cells can address these therapeutic challenges. Mechanized silica nanoparticles (MSNPs) based drug delivery vehicles have the ability to improve drug distribution, cell or tissue specific targeting, and drug espoused kinetics, resulting in enhanced efficacy and improved tolerability. The development of drug delivery systems, which administers medically active compounds to diseased cells in a targeted and controlled manner and at the same time capable to produce synergic actions through well-organized multidrug release systems, is the main objective of this proposal. The recognition motifs of ß-CD rings were movable and the pH-responsive linkers were immobilized on the surface of the MSNPs. An adaptable platform for drug delivery has been developed by employing MSNPs as scaffolds and using the robust ß-cyclodextrinadamantane (ß-CD/AD) inclusion complex as a universal surface linker. We have functionalized adamantane with poly(ethylene glycol) and BODIPY to create biocompatabilizing and imaging pendant groups respectively.

At the initiation of this project, the initial design for cell selectivity involved utilization of surface functionalize cyclodextrins as supramolecular anchoring units to display targeting ligands in conjunction with biocompatabilizers and imaging agents. Using this approach, we hoped to achieve a multifunctional platform technology with exposed ligands that interact with cell receptors on cell surfaces. Additionally, the supramolecular design of this system would provide self-assembly of the components in one step, based on competitive binding equilibria. To achieve chemotherapeutic applications, probe or drug molecules could be loaded into the mesoporous particles, followed by end capping of the pores with per-aminomodified cyclodextrin units.

In this project, we aim to design customized nanocarriers by functionalizing the surfaces of mesoporous silica nanoparticles (MSNPs) so as to endow them with water-solubilizing groups and multiple copies of cancer cell-specific targeting moieties (peptides, aptamers or antibodies) in order to address, with one nanoparticle vehicle, the challenges of targeted drug delivery.

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