Cancer is a leading cause of death worldwide, with more than 10 million deaths reported in 2020. Leukemia is a type of blood cancer that can be difficult to treat in adults, requiring the development of Smart Drug Delivery Systems (SDDS). SDDS employ the use of nanoparticles (NPs) for targeted drug delivery. NPs are typically defined as falling in the size range of 1 – 1,000 nanometers. Nanotechnology has profound applications, specifically in the field of drug delivery. This includes nanocarriers as delivery vehicles, including polymeric NPs, quantum dots, liposomes, micelles, and many others. Polymeric NPs are synthesized using polymers. For instance, poly-L-lysine (PLL), a cationic polymer, is regularly employed to foster self-assembly in NPs formation. poly(ethylene glycol) (PEG) can be grafted to PLL to offer protection from proteolytic degradation. L-asparaginase (L-ASNase) is a therapeutic protein used to treat leukemia. Its mechanism involves converting asparagine (L-ASN) into aspartic acid, thereby depleting circulating asparagine a vital nutrient for cellular growth and protein synthesis. Leukemia cells are unable to produce asparagine and require an exogenous source and hence L-ASNase triggers asparagine starvation and cell death of leukemic cells. However, L-ASNase is hindered by a short circulatory half-life, diminished enzymatic activity under physiological conditions, and overall low stability. Previous research has demonstrated the encapsulation of L-ASNase in polyl- lysine grafted poly(ethylene glycol) (PLL-g-PEG) nanocarriers to mitigate these drawbacks. Doxorubicin (DOX) is a small-molecule chemotherapeutic drug that is a topoisomerase II inhibitor. Topoisomerase II is necessary for transcription and DNA replication by repairing damaged or tangled DNA. DOX prevents topoisomerase II from repairing DNA, causing cell death. Co-encapsulation has emerged as a promising area of research. Co-encapsulation is the combining of multiple therapeutics into one nanocarrier. This presents unique challenges due to the different physicochemical characteristics of therapeutic molecules. This research investigates the co-encapsulation of DOX and L-ASNase within a PLL-g-PEG polymer nanocarrier. The main goal of this research is to evaluate the co-encapsulation of DOX and L-ASNase within PLL-g-PEG NPs. Three different types of NPs have been synthesized: LASNase NPs, L-ASNase/DOX NPs, and L-ASNase/BSA-DOX NPs. These sets were synthesized to compare and evaluate two different methods of co-encpasulation. The specific tasks of this research were to (1) synthesis and characterization of L-ASNase and DOX encapsulated PLL-g- PEG NPs, (2) conjugation of DOX to Bovine Serum Albumin (BSA) through DTSSP linker and characterization using attenuated total reflectance Fourier transform infrared (ATR-FTIR) and ultraviolet-visible (UV-Vis) spectroscopy, (3) evaluation of NPs size, surface charge, and morphology through dynamic light scattering (DLS) and scanning transmission electron microscopy (STEM), (4) evaluation of the extent of protein/drug encapsulation (encapsulation efficiency) and stability using gel electrophoresis and DOX calibration curves, and (5) determination of LASNase activity within NPs. In this study, we successfully synthesized co-encapsulated DOX and L-ASNase PLL-g-PEG polymer NPs. DOX was conjugated to the surface of BSA through a reducible linker to stabilize DOX within the NPs. The NPs were formed through self-assembly caused by electrostatic interactions between cationic co-polymer and negatively charged conjugates and proteins. LASNase/ BSA-DOX NPs demonstrated lower size variability and smaller hydrodynamic diameters, averaging around 84.8 ± 48.0 nm. L-ASNase activity was not conversely affected more than typically observed from encapsulation of L-ASNase. BSA-DOX conjugates showed a higher affinity for NPs formation over L-ASNase, resulting in decreased L-ASNase encapsulation efficiencies ranging from 75 – 94%. DOX remains stably encapsulated within L-ASNase/BSA-DOX NPs, producing high DOX encapsulation efficiencies. This method of co-encapsulation serves as a model for the co-encapsulation of other proteins and small molecule drugs.