Photopolymerization Synthesis of Magnetic Nanoparticle Embedded Nanogels for Targeted Biotherapeutic Delivery

Conventional therapeutic techniques treat the patient by delivering a biotherapeutic to the entire body rather than the target tissue. In the case of chemotherapy, the biotherapeutic is a drug that kills healthy and diseased cells indiscriminately which can lead to undesirable side effects. With targeted delivery, biotherapeutics can be delivered directly to the diseased tissue significantly reducing exposure to otherwise healthy tissue. Typical composite delivery devices are minimally composed of a stimuli responsive polymer, such as poly(N-isopropylacrylamide), allowing for triggered release when heated beyond approximately 32 °C, and magnetic nanoparticles which enable targeting as well as provide a mechanism for stimulus upon alternating magnetic field heating. Although more traditional methods, such as emulsion polymerization, have been used to realize these composite devices, the synthesis is problematic. Poisonous surfactants that are necessary to prevent agglomeration must be removed from the finished polymer, increasing the time and cost of the process. This study seeks to further explore non-toxic, biocompatible, non-residual, photochemical methods of creating stimuli responsive nanogels to advance the targeted biotherapeutic delivery field. Ultraviolet photopolymerization promises to be more efficient, while ensuring safety by using only biocompatible substances. The reactants selected for nanogel fabrication were N-isopropylacrylamide as monomer, methylene bisacrylamide as cross-linker, and Irgacure 2959 as ultraviolet photo-initiator. The superparamagnetic nanoparticles for encapsulation were approximately 10 nm in diameter and composed of magnetite to enable remote delivery and enhanced triggered release properties. Early investigations into the interactions of the polymer and nanoparticles employ a pioneering experimental setup, which allows for coincident turbidimetry and alternating magnetic field heating of an aqueous solution containing both materials. Herein, a low-cost, scalable, and rapid, custom ultraviolet photo-reactor with in-situ, spectroscopic monitoring system is used to observe the synthesis as the sample undergoes photopolymerization. This method also allows in-situ encapsulation of the magnetic nanoparticles simplifying the process. Size characterization of the resulting nanogels was performed by Transmission Electron Microscopy revealing size-tunable nanogel spheres between 50 and 800 nm by varying the ratio and concentration of the reactants. Nano-Tracking Analysis indicates that the nanogels exhibit minimal agglomeration as well as provides a temperature-dependent particle size distribution. Optical characterization utilized Fourier Transform Infrared and Ultraviolet Spectroscopy to confirm successful polymerization. When samples of the nanogels encapsulating magnetic nanoparticles were subjected to an alternating magnetic field a temperature increase was observed indicating that triggered release is possible. Furthermore, a model, based on linear response theory that innovatively utilizes size distribution data, is presented to explain alternating magnetic field heating results. The results presented here will advance targeted biotherapeutic delivery and have a wide range of applications in medical sciences like oncology, gene delivery, cardiology and endocrinology