Targeted Delivery and Macrophage Reprogramming for Tumor Suppression

Current cancer treatments rely on systemic drug delivery where chemotherapeutic drugs kill both healthy and cancerous cells. This leads to negative side effects such as alopecia, nausea, fatigue, and anemia. Targeted and controlled delivery of chemotherapeutic drug could mitigate side effects and improve cytoxicity to cancer cells. Additional tumor suppression can be achieved through reprogramming of macrophages. Macrophages can be polarized to produce pro-inflammatory (M1) or pro- angiogenic (M2) molecules. M2 macrophages promote tumor growth through the release of angiogenic molecules, while M1 macrophages produce molecules that are toxic to tumor cells. Tumor-associated macrophages (TAMs) are thought to be M2. Certain material properties are known to reprogram macrophages from M2 to M1. Our project looks to use controlled drug delivery in conjunction with macrophage reprogramming in order to improve cancer treatment efficacy. Polymeric systems are being investigated for their potential to reprogram TAMs and to deliver anti-cancer therapeutics to tumors.  Here, we focus on alginate nanoparticles coated with poly-L-arginine (PLR).  We have shown that alginate nanoparticles coated with PLR bearing different functional groups can alter the release kinetics of chemotherapeutic drug. In addition, we have shown that differing functional groups associated with the PLR-coated nanoparticles have the ability to alter the number of particles internalized by both cancer cells and macrophages. Methods for nanoparticle internalization in both cancer cells and macrophages are being analyzed for future work in developing specialized delivery devices. The ability to use polymeric systems for both macrophage reprogramming and targeted delivery of anti-cancer drug has the potential to significantly impact cancer therapy.