Green Manufacturing of Nanoparticles for Biomedical Applications

The vast majority of nanomaterials are chemically synthesized, a costly process, that is environmentally risky, and the produced nanoparticles are potentially toxic to patients. Nature-based nanomaterials, however, are proving to be much more biocompatible with lower environmental toxicity. Even though a variety of natural nanomaterials have been designed, fabrication technologies for the desired natural nanoparticles with reproducible quality, high productivity and low cost remain a challenge. My objective has been to establish strategies for the isolation, purification and characterization of nanoparticles using a production system based on green tea and fungus (Arthrobotrys oligospora) and also to develop new approaches for sustainable “green manufacture” of gold nanoparticles for biomedical applications. First, an infusion-dialysis procedure to isolate of the tea nanoparticles (TNPs) from a green tea infusion was developed and validated. The TNPs are spherical with a diameter of 100-300 nm, and have a zeta potential of -26.52 mV at pH 7.0. The TNPs enhance secretion of the cytokines and the chemokines from mouse macrophages, suggesting a potential immunostimulatory effect. As a natural nanocarrier, the TNPs are able to form complexes with doxorubicin (DOX). The DOX-loaded TNPs increase cellular DOX uptake, leading to higher cytotoxicity in cancer cells. Second, a new isolation procedure was established to purify the fungal nanoparticles (FNPs) from A. oligospora, giving two purified FNP fractions. Both purified FNPs had a reduced diameter of 100-200 nm, with glycosaminoglycan as the main constituent. The purified FNPs cause mild cytotoxicity by inducing apoptosis and regulating the cell cycle in multiple tumor cell lines and have an immunostimulatory effect. Additionally, the FNPs have an immunochemotherapeutic effect upon complexing with DOX against tumor cells. Third, a sustainable system for green manufacturing of gold nanoparticles was developed by using actively growing English ivy. The efficient uptake of the synthesized gold nanoparticles in mammalian cells provides the potential for biomedical applications. Finally, a simple one-step approach using dopamine, a monoamine neurotransmitter appearing naturally in the human brain, to synthesize highly branched gold nanoflowers (AuNFs) was developed. These AuNFs are highly biocompatible and provide high surface enhanced Roman scattering (SERS) performance.