Protein-based therapeutics comprise a rapidly growing subset of pharmaceuticals, yet the transport of proteins across cell membranes has been a longstanding issue in the field. The potential of proteins as efficacious intracellular therapeutic agents has been highlighted in the use of novel protein scaffolds that inhibit “undruggable” biological targets and more recently by gene-editing machinery for treating human disease. Translating many of these promising technologies for clinically relevant applications requires the development of delivery methods capable of translocating proteins into the cytosol of a cell for functional activity. To overcome the delivery barrier, we explored a generalizable platform for protein delivery by adopting lipid nanoparticle (LNP) formulations that have found great clinical success in the delivery of nucleic acids. This thesis will outline the development of a reversible, bioconjugation-based approach to modify the surface charge of protein cargos with an anionic “cloak” to facilitate electrostatic complexation and delivery with LNP formulations. We demonstrate that the conjugation of lysine-reactive sulfonated compounds can allow for the delivery of various protein cargos using FDA-approved LNP formulations of the ionizable cationic lipid DLin-MC3-DMA (MC3). We apply this strategy to functionally deliver RNase A for cancer cell killing as well as a full-length antibody to inhibit oncogenic beta-catenin signaling. Further, we show that LNPs encapsulating cloaked fluorescent proteins distribute to major organs in mice following systemic administration. In the second part of our work, we build on our cloaking platform to optimize the delivery of full-length IgG antibodies into cells using LNP formulations, with the goal of enabling intracellular targeting of disease-relevant proteins. This strategy is used to efficiently deliver various off-the-shelf antibodies into multiple cancer cell lines, achieving potent inhibition of key transcription factors involved in inflammatory and cancer signaling pathways, including the NF-kB, Wnt, and JAK-STAT pathways. We also apply this platform to enable systemic delivery of antibodies encapsulated in LNPs to major organs in mice and achieve enhanced delivery to the lungs. The lung-targeting capabilities of our system were further expanded upon by implementing this approach to deliver therapeutic antibodies to attenuate inflammation in a mouse model of acute lung injury (ALI). Overall, our results point toward a generalizable platform that can be employed for intracellular delivery of a wide range of protein cargos. Ultimately, the goal of this thesis is to help bridge the gap that exists between the ongoing advancements in protein therapeutics and the current lack of efficient delivery techniques for introducing these novel therapies inside of cells.