DescriptionAlpha-particle emitting radionuclides are a promising class of emitters for the treatment of cancer. Emitted alpha-particles deposit considerable energy along a short-ranged trajectory (<100 µm), allowing the potential for highly localized and cytotoxic irradiation of cancer while sparing the surrounding healthy tissues from off-target effects. The majority of alpha-particle therapies under development are radioimmunoconjugates, which are effective in treating easily-accessible or volumetrically small target sites such as tumor vasculature, micrometastases, or liquid tumors such as leukemia. However, radiolabeled antibodies possess certain limitations such as low specific activity and potentially sub-optimal intracellular localization. Additionally, the limited penetration of solid tumor mass due to the binding site barrier effect combined with short alpha-particle trajectory effectively precludes the use of alpha-particle radioimmunoconjugates from effectively treating bulky solid tumors. To date, the use of liposome-mediated delivery of alpha-particle emitters to overcome these limitations has not been explored. In this dissertation, we describe delivery of the alpha-particle emitting radionuclide Actinium-225 (225Ac) mediated with liposomal nanoparticles. We investigate the anti-solid tumor potential of 225Ac-liposomes by evaluating its efficacy against analogues of tumor vasculature and avascular solid tumors. Overall, our results suggest the feasibility of a liposomal approach in the therapy of solid, vascularized tumors.