Biocompatible Nanomedicine for Advanced Tumor Diagnostics and Therapy

Abstract

Within the rapid advances in the field of biotechnology and the growing interest in developing new methods for precise diagnosing and treating diseases, the potential of nanoparticles plays a crucial role to overcome the limitations of traditional therapy. Owing to their unique properties, including size, exceptional catalytic features, and advanced optical performance, they are regarded as superior materials. However, rapid aggregation, non-specific accumulation, and other problems could be encountered with nanoparticles, leading to potential toxicity and inhibiting their promising utilization. Therefore, a particularly promising approach is the use of biocompatible nanoparticle-based drug delivery systems, which reduce concerns about toxicity. These systems enable the delivery of therapeutic agents, such as drugs or proteins, while preserving their unique properties and protecting the drugs. Also, it is important to increase the blood circulation time of nanoparticles and ensure the stable delivery of cargo to the target site through novel nanoparticle design. In this context, this dissertation focuses on proposing enhanced strategies to improve nanoparticle properties and employing unique approaches in drug delivery systems to increase their efficacy in biomedical applications. We first developed a general strategy to improve nanoparticle biocompatibility, enhancing cell recognition and intracellular siRNA delivery. PEGylation emerged as a key strategy to avoid opsonization and minimize nonspecific accumulation in off-target cells. Unlike previous studies focusing on non-specific nanoparticles with smooth surfaces, we have demonstrated that secondary packaging with shorter PEG chains in porous nanoparticles significantly enhances anti-opsonization and active targeting, leading to improved intracellular delivery of these nanoparticles. Furthermore, the optical bioimaging of nanoparticles has significantly contributed to modern biology and medicine by providing spatiotemporal precision and control. Despite its many merits such as high sensitivity, multimodal imaging and biocompatibility, this technique still faces many challenges, particularly tissue autofluorescence interference. To overcome this issue, we design long-lived room-temperature phosphorescence silica material as a high-contrast bioimaging probe. The facile surface modification of water-soluble silica nanoparticles with tumor-homing peptide enabled precise tumor diagnosis by providing the tissue autofluorescence-free in vivo bioimaging. Gene therapy is a promising therapeutic approach for diseases related to heritable or somatic mutations, but traditional viral vectors, such as lentiviral vectors, adenoviral vectors, and adeno-associated viral vectors, face severe challenges associated with immunogenicity and ethical concerns despite their high delivery efficiency. To address these obstacles, we utilized the lipid nanoparticles for delivering the Clustered Regularly Interspaced Short Palindromic Repeat/CRISPR-associated (CRISPR/Cas) protein system. We have demonstrated that the CRISPR/Cas system delivered via lipid nanoparticles enables the specific and precise introduction of DNA modifications into living cells. These studies provide strong evidence that the LNP-based delivery method can effectively target and edit genetic material within the cellular environment, highlighting its potential for therapeutic applications in gene therapy and genetic research. Taken together, this work contributes to the field of biotechnology with innovative approaches in nanoparticle engineering and provides significant advancements in the stability, specificity, and efficiency of precision medicine