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With the remarkable advancement in the nanoparticles (NPs)-based drug delivery systems (DDS) over the past several decades, the pharmacological properties associated with conventional free drugs delivery are improved. In this thesis, we report potential candidates for the next-generation NP-based DDS. While natural DDS are promising as they possess exceptional delivery mechanisms and selective targeting, synthetic DDS are more favorable for their low immunogenicity. Our developed natural DDS called magnetotactic bacterial cages (MBC), which is based on magnetotactic bacteria (MTB) as a guidable delivery vehicle for DNA functionalized gold nanoparticles (AuNPs). Loading DNA functionalized AuNPs in MTB aided in increasing the maximum-tolerated dose of DNA functionalized AuNPs and tackled issues related to DNA functionalized AuNPs stability and systemic delivery. Natural DDS hold great advantages; however, it is difficult to make complete prediction about their immunogenicity and toxicity on the basis of preclinical trials. Thus, we assessed the efficacy of synthetic NP-based DDS. Using inorganic platforms, we were able to develop the first visual monitoring system of bacteria-NPs interaction. The system offers simultaneous sensing and inhibition of bacteria in infected cells. The system is comprised of Au nanoclusters @lysozyme (AuNC@lys) colloids MSN loaded with antibacterial agents. The applicability of the inorganic DDS in the biomedical field has been limited by the high bioaccumulation risks. Hybrid materials combine the advantages of organic, inorganic and natural carriers, offering opportunities for enhanced stability, manipulating release behavior and combine two or more functions in a single platform. To further enhance the properties our inorganic DDS, we incorporated light-responsive organic ligands to silicabased NPs. Plasmid DNA was loaded on the light-responsive bridged silsesquioxane nanocomposites (BS NPs). Light irradiation was performed to reverse the surface charge of NPs via a photoreaction of the organic fragments (silsesquioxane) within the NPs, that resulted in the release of plasmid DNA in HeLa cancer cells. Finally, we assessed a new class of organic-inorganic DDS composed of inorganic metal ions and organic linkers, zeolite imidazolate frameworks-8 (ZIF-8). These NPs showed exceptional ability to entrap large cargo due to their tunable porosity and structural flexibility.

During the past few years, gold nanoparticles (AuNPs) have received considerable attention in many fields due to their optical properties, photothermal effect and biocompatibility. AuNPs, particularly AuNCs and AuNRs, exhibit great potential in diagnostics and imaging. In the present study, AuNCs were used to selectively image and quantify intracellular antioxidants. It was reported by Chen et al. that the strong fluorescence of AuNCs is quenched by highly reactive oxygen species (hROS). Most of applications depend on fluorescence quenching, however, for our project we designed turn-on fluorescent sensors using AuNCs that sense antioxidants. In the presence of antioxidants, AuNCs fluorescence switch on, while in the absence of antioxidants their fluorescence immediately turn off due to hROS effect. AuNRs were also used for cellular imaging in which AuNRs were conjugated to Cy3-labelled molecular beacon (MB) DNA. Next, the previous complex was loaded in two different strains of magnetotactic bacteria (MTB). MTB were used as a targeted delivery vehicle in which magnetosomes direct the movement of bacteria. The DNA sequence was specific to a certain sequence in mitochondria. The exposure of MTB to an alternating magnetic field (AMF) leads to the increase of temperature inside the bacteria, which destruct the cell wall, and hence, bacterial payload is released. When MD-DNA hybrid with the target sequence, AuNR and Cy3 separate from each other, the fluorescence of the Cy3 is restored.