MXene and polydopamine-based multifunctional nanocomposites for cancer therapy and biosensing

Abstract

The advancement of nanotechnology in recent years has led to the development of various nanomaterials with unique physical and chemical properties. Multifunctional nanocomposites, which integrate different functionalities into one nano-system, have garnered significant attention. Compared to single-mode nanomaterials, these multifunctional nanocomposites exhibit superior performance, distinct multifunctionality, and high customizability. MXene, a novel two-dimensional material, has gain substantial interest due to its favorable properties. It has been applied as a photothermal agent to design multifunctional nanocomposites for cancer therapy. In addition, MXene has been utilized to construct optical biosensors, including SERS and fluorescence sensors, due to its exceptional Raman enhancement effect and high light absorption ability. Polydopamine (PDA), a melanin-inspired nanomaterial derived from the polymerization of dopamine, offers several benefits, including straightforward synthesis, cost-effectiveness, superior photothermal capabilities, robust adhesiveness, and commendable biocompatibility. Given these attributes, numerous studies have used PDA as a drug delivery vehicle for various therapeutic modalities of cancer. This thesis focuses on the development and application of MXene and PDA-based multifunctional nanocomposites for cancer therapy and biosensing. In the first project, we address the instability problem of MXene by using PDA as a protective layer through a facile and low-cost method. The resultant PDA@MXene nanoparticles demonstrate improved stability and photothermal conversion efficiency, making them promising candidates for photothermal agents. Glucose oxidase (GOX) was loaded onto the surface of PDA@MXene to generate PDA@MXene@GOX nanocomposites for tumor photothermal/starvation synergistic therapy. Comprehensive in vitro and in vivo studies jointly demonstrate the efficacy of PDA@MXene@GOX in inhibiting tumor cell proliferation, highlighting its potential to overcome the limitations of individual photothermal or starvation therapies. The second part of this thesis involves the development of a fluorescence/SERS dual-mode endotoxin biosensor, combining the properties of MXene nanosheets and the CRISPR/Cas12a system. This biosensor, employs MXene nanosheets loaded with Au nanoparticles, acting as both a fluorescence quencher and a SERS enhancer, demonstrating high sensitivity and specificity, The Cas12a system is capable of specifically recognizing the endotoxin aptamer through a specially engineered PAM recognition sequence. This dual-mode detection strategy not only provides excellent sensitivity and specificity for endotoxin detection but also reduces the likelihood of false positives, thereby enhancing the overall reliability of the results. The third part of this thesis focuses on enhancing and monitoring therapeutic outcomes of immune checkpoint blockade (ICB) therapy by developing an ICB therapy and immune response monitoring multifunctional nanoprobe. This nanoprobe, constructed from PDA nanoparticles and graphene quantum dots (GQD), is engineered to simultaneously execute LILRB4 blocker mediated ICB therapy and monitor therapeutic effects by detecting the expression level of Granzyme B (GrB). Both in vitro and in vivo evaluations demonstrate the nanoprobe's feasibility and multi-level efficacy. Consistent findings highlight the nanoprobe's ability to concurrently administer LILRB4 blocker-mediated ICB therapy and monitor therapeutic outcomes, indicating it as a promising tool for advanced biomedical applications.