Hollow-sphere nanocapsules containing intentionally trapped magnetic nanoparticles and defined anticancer drugs provide a powerful magnetic vector under moderate gradient magnetic fields, and enable the nanocapsules to penetrate into the midst of tumors and allow a controlled on-off switchable release of the anticancer drug cargo by remotely applied Radio Frequency (RF) magnetic field. This imageable smart drug delivery system is compact because the drug molecules and magnetic nanoparticles can all be self-contained within 801̃50 nm capsules. In vitro as well as in vivo results indicate that the nanocapsules are effective in reducing tumor cell growth. In Chapter 1, the concept of Drug Delivery Systems (DDSs) and the impact of nanotechnology on Drug Delivery Systems were introduced. Triggered drug release using magnetothermally-responsive nanomaterials, magnetic nanoparticles for nanomedicine, and ordered mesoporous materials in the context of Drug Delivery System were discussed. In Chapter 2, creation of remotely controllable, On-Off switchable drug release methodology was described. In this thesis work, triggerable nanocapsules which contain magnetic nanoparticles responsive to external radio frequency (RF) magnetic field have been successfully created. This is in contrast to the regular hollow nanospheres for slow passive release of drugs. The new nanocapsule material consists of bio-inert, bio-compatible or bio-degradable material that we can be selected from a variety of materials depending on specific medical applications. In Chapter 3, study and utilization of magnetic vector for guided tumor penetration was discussed. In the presence of a moderate gradient magnetic field, a powerful magnetic vector is created that allows these nanocapsules to cross cell membranes or blood-tissue barriers and penetrate into the midst of tumors, thus overcoming the well-known problem of limited access of anti-cancer drugs to cancer cells in the interior of a tumor tissue. In Chapter 4, potential applications to Blood-Brain-Barrier (BBB) crossing and other therapeutics was described. In Chapter 5, the study was summarized and concluded

Podocyte, the gatekeeper of the glomerular filtration barrier, is a primary target for growth factor and Ca²⁺ signaling whose perturbation leads to proteinuria. However, the effects of insulin action on store-operated Ca²⁺ entry (SOCE) in podocytes remain unknown. Here, we demonstrated that insulin stimulates SOCE by VAMP2-dependent Orai1 trafficking to the plasma membrane. Insulin-activated SOCE triggers actin remodeling and transepithelial albumin leakage via the Ca²⁺-calcineurin pathway in podocytes. Transgenic Orai1 overexpression in mice causes podocyte fusion and impaired glomerular filtration barrier. Conversely, podocyte-specific Orai1 deletion prevents insulin-stimulated SOCE, synaptopodin depletion, and proteinuria. Podocyte injury and albuminuria coincide with Orai1 upregulation at the hyperinsulinemic stage in diabetic (db/db) mice, which can be ameliorated by the suppression of Orai1-calcineurin signaling. Our results suggest that tightly balanced insulin action targeting podocyte Orai1 is critical for maintaining filter integrity, which provides novel perspectives on therapeutic strategies for proteinuric diseases, including diabetic nephropathy.