Abstract
In the recent clinical scenario, phototherapies are widely explored for the treatment of various types of cancers. The major advantages of phototherapies include non-invasiveness, superior tissue penetration, reduced side effects and cost-effective treatment strategies than other modalities. Photodynamic therapy (PDT) is one of the very important phototherapeutic approaches which involve the use of an organic photosensitizer (PS) molecule to absorb and transfer the photon energy to the normal tissue oxygen (3O2) to generate cytotoxic singlet oxygen (1O2), which is able to kill cancer cells. Most of the clinical PDT treatments are restricted to surface tumors, because most of organic PS can only be photochemically excited by either UV or visible light, which have very short tissue penetration depths. The organic PS molecules are usually insoluble in water, possesses very poor light absorbing capabilities, and also prone to severe photobleaching and enzymatic degradation. Therefore, it leaves a grand challenge to develop a novel and exciting treatment modality which can overcome the drawbacks of conventional PDT. In this regard, the advent of nanotechnology brings a lot of hope to the clinical biomedicine. Fabrication of nanomaterials with extra-ordinary light absorbing capabilities extending the visible to near infra-red regions, excellent photostabilities, high surface area, magnetic and fluorescent properties are actually very rare and limited. In this thesis, we have explored such variety of nanomaterials which can mediate the photodynamic therapeutic effects without any co-presence of organic photosensitizers and capable of activation by NIR light for the treatments of skin and lung cancers. In the first chapter, we have developed a theranostic nanoconstruct based on lanthanide doped mesoporous silica nanoparticles (EuGd@MCF) loaded with an anticancer drug, doxorubicin (DOX) can facilitate simultaneous magnetic resonance (MR) / fluorescence imaging and can also sensitize formation of singlet oxygen (1O2) upon near-infra red (NIR) light irradiation to exert the combination of chemo-photodynamic therapeutic (PDT) effects to kill the cancer cells/solid tumors. In the second chapter, we have presented an unprecedented phenomenon of photosensitization of singlet oxygen and its photodynamic therapeutic (PDT) effects mediated by PEGylated tungsten oxide nanowires (PEG-W18O49 NWs) on destruction of cancer cells/malignant tumors. In the PEG-W18O49 NWs internalized HeLa cells, we show that at low laser intensity (980 nm, 200 mW/cm2), cancer cells die from PDT-initiated apoptosis with a very minor contribution coming from the photothermal therapy (PTT) effect-initiated apoptosis. Direct evidences such as, singlet oxygen, reactive oxygen species (ROS) formation and heat shock protein (HSP 70) expression were also provided to show the existence of PDT and PTT pathways. In the in vivo experiments, the PEG-W18O49 NWs-mediated PDT effects are far more effective in destructing B16F0 melanoma tumors than the corresponding PEG-W18O49 NWs -mediated PTT effects at low doses of NIR light irradiation. In the third chapter, we have showed that upconversion nanoparticles (UCNPs) can sensitize formation of singlet oxygen (1O2) and exert in vivo photodynamic therapeutic effects upon NIR (980 nm) light excitation at very low laser doses (70~360 mW/cm2), in addition to the upconversion fluorescence emission. In combination with the silencing gene, superoxide dismutase (SOD1), the upconversion nanoparticles-mediated combination therapeutic modality can effectively kill lung tumors. Further, in the chapter four, we have extended the similar study to PEGylated nano graphene oxide conjugated with the folate (GO-PEG-folate) to develop as a nanomaterial-mediated PDT reagent for the destruction of melanoma tumors upon activation by 980 nm NIR light. Overall, the current thesis provides an overview of how the intrinsic nanomaterials can be used as photodynamic therapeutic reagents in killing cancer cells without the use of any organic photosensitizers. Taken altogether, we have discovered the field of nanomaterial-mediated photodynamic therapy (NmPDT), as an exciting alternative to organic PS-mediated PDT and nanomaterial-mediated photothermal therapy (NmPTT) for the clinical cancer treatments.