UCLA

There is currently a high unmet medical need for chemotherapy and early diagnostics for cancer. Conventional direct administration of chemotherapeutic agents shows several major drawbacks, including restricted cellular penetration, low therapeutic indices, and low specificity to tumor cells thus consequently off-target toxicity in healthy cells. Nanoparticles with enhanced permeability and retention (EPR) effect provide both delivery and diagnostic modalities and show promise for addressing these challenges in cancer therapy. Superparamagnetic iron oxide nanoparticles (SPIONs) that respond to external magnetic fields can generate heat in the presence of an alternating magnetic field (AMF). Owing to this unique property, SPIONs are being used in clinics as magnetic resonance imaging T2 contrast agents and as AMF-induced therapeutic agents to treat cancers. Mesoporous silica nanoparticles embedded with SPIONs (SPION@MSNs) possess the advantageous features of both the SPION core and the shell, i.e., localized magnetic heating and a high payload of various cargo molecules such as anticancer drugs. A part of this dissertation focuses on the development of SPION@MSNs as a heat-activated drug delivery platform in which the precise drug release can be directly controlled by using AMF. To expand our knowledge base in this application, we first studied the local heating mechanism of SPIONs in suspension and in MSNs. We carried out this investigation by using fluorescence depolarization based on detecting the mobility-dependent polarization anisotropy of two luminescence emission bands corresponding to the luminescent SPION core and the shell of the SPION@MSNs. Utilizing magnetic heating, we designed magnetically activated and enzyme-responsive SPION@MSNs with extra-large pores for in vivo delivery and release of anticancer peptides on-demand. In addition, we introduced the design of MSNs-based delivery vehicles with a supramolecular capping system that traps the cargos in the pores of nanoparticles and only releases the cargos in response to ultrasound. Finally, by employing surface functionalization of silica, we developed new fluorinated ferrofluids that can be encapsulated in a microdroplet for measuring microenvironment stiffness, which has been shown to relate to tumor progression. Altogether, these works show the full potential of SPION core/shell nanoparticles for advancing cancer therapy and diagnostic.