Correction to "Luminescent Gold Nanocluster-Decorated Polymeric Hybrid Particles with Assembly-Induced Emission"

Correction to “Luminescent Gold Nanocluster-Decorated Polymeric Hybrid Particles with Assembly-Induced Emission

Gold-Silica Quantum Rattles for Cancer Therapy and Diagnosis

The Holy Grail of cancer research is to find effective treatments that can be easily delivered to diseased cells with minimal collateral damage to healthy tissue. In this context, recent developments in nanoparticle technology have aroused considerable interest with the promise of multifunctional vectors for both diagnostic and treatment of cancer. Recently, new emphasis has been placed on hybrid nanoparticle (NP) systems, where combinations of different types of nanostructured materials are used to create multimodal systems that exhibit the combined beneficial properties of the component modules. In particular, nanorattles, which are NPs with a core-shell structure containing a distinctive void separating the core material from the shell, constitute promising launch platforms for many biomedical applications. Current hybrid NP systems tend to concentrate on adding extra properties by increasing the number of modules and therefore, system complexity. However, added complexity in itself does not guarantee higher effectiveness. Therefore, in this thesis, a more holistic approach is proposed whereby simplicity, efficiency and usefulness of the design are not overlooked. The work presented here describes a gold-silica rattle-type particle, the Quantum Rattle (QR), made of a hollow mesoporous silica shell (HS) hosting two classes of hydrophobic gold nanostructures: gold quantum dots (AuQDs) and gold nanoparticles (AuNPs). The HS stabilises the gold nanostructures, making them dispersible in water and thereby enables biomedical applications. It also allows passive targeting for the QR via the enhanced permeability and retention (EPR) effect. The AuQDs absorb and emit light in the near-infrared (NIR) biological window where blood and soft tissue are relatively transparent (650 nm - 900 nm). With their NIR photonics, the AuQDs mediate both photothermal therapy (PPT) and live infrared imaging. Finally, the hydrophobic AuNPs optimise the system’s drug carrying performance by increasing the payload’s loading efficiency as well as controlling its release profile. This thesis exhibits the first evidence of the intrinsic and efficient therapeutic and diagnostic potential of this new class of hybrid NP system and discusses how these results could have a significant impact on the growing field of nanosystems used for cancer treatment

Heterofunctional Poly(ethylene glycol) (PEG) Macroinitiator Enabling Controlled Synthesis of ABC Triblock Copolymers

ABC triblock copolymers with a poly­(ethylene glycol) (PEG) midblock have attractive properties for biomedical applications because of PEG’s favorable properties regarding biocompatibility and hydrophilicity. However, easy strategies to synthesize polymers containing a PEG midblock are limited. In this study, the successful synthesis of a heterofunctional PEG macroinitiator containing both an azoinitiator and an atom transfer radical polymerization (ATRP) initiator is demonstrated. This novel PEG macroinitiator allows the development of elegant synthesis routes for PEG midblock-containing ABC copolymers that does not require protection of initiating sites or polymer end-group postmodification. Polymers with outer blocks composed of different monomers were synthesized to illustrate the versatility of this macroinitiator. <i>N</i>-Isopropylacrylamide (NIPAM) was included to obtain thermosensitive polymers, 2-(dimethylamino)­ethyl methacrylate (DMAEMA) provided pH-sensitive properties, and 2-hydroxyethyl acrylate (HEA) functioned as a noncharged hydrophilic block that also allows for postmodifications reactions. This synthesis approach can further contribute to the design of high-precision polymers with tailorable block compositions and polymer topologies, which is highly attractive for applications in nanotechnology

Heterofunctional Poly(ethylene glycol) (PEG) Macroinitiator Enabling Controlled Synthesis of ABC Triblock Copolymers

ABC triblock copolymers with a poly(ethylene glycol) (PEG) midblock have attractive properties for biomedical applications because of PEG's favorable properties regarding biocompatibility and hydrophilicity. However, easy strategies to synthesize polymers containing a PEG midblock are limited. In this study, the successful synthesis of a heterofunctional PEG macroinitiator containing both an azoinitiator and an atom transfer radical polymerization (ATRP) initiator is demonstrated. This novel PEG macroinitiator allows the development of elegant synthesis routes for PEG midblock-containing ABC copolymers that does not require protection of initiating sites or polymer end-group postmodification. Polymers with outer blocks composed of different monomers were synthesized to illustrate the versatility of this macroinitiator. N-Isopropylacrylamide (NIPAM) was included to obtain thermosensitive polymers, 2-(dimethylamino)ethyl methacrylate (DMAEMA) provided pH-sensitive properties, and 2-hydroxyethyl acrylate (HEA) functioned as a noncharged hydrophilic block that also allows for postmodifications reactions. This synthesis approach can further contribute to the design of high-precision polymers with tailorable block compositions and polymer topologies, which is highly attractive for applications in nanotechnology

Gold Nanoclusters: Imaging, Therapy, and Theranostic Roles in Biomedical Applications

For the past two decades, atomic gold nanoclusters (AuNCs, ultrasmall clusters of several to 100 gold atoms, having a total diameter of <2 nm) have emerged as promising agents in the diagnosis and treatment of cancer. Owing to their small size, significant quantization occurs to their conduction band, which leads to emergent photonic properties and the disappearance of the plasmonic responses observed in larger gold nanoparticles. For example, AuNCs exhibit native luminescent properties, which have been well-explored in the literature. Using proteins, peptides, or other biomolecules as structural scaffolds or capping ligands, required for the stabilization of AuNCs, improves their biocompatibility, while retaining their distinct optical properties. This paved the way for the use of AuNCs in fluorescent bioimaging, which later developed into multimodal imaging combined with computer tomography and magnetic resonance imaging as examples. The development of AuNC-based systems for diagnostic applications in cancer treatment was then made possible by employing active or passive tumor targeting strategies. Finally, the potential therapeutic applications of AuNCs are extensive, having been used as light-activated and radiotherapy agents, as well as nanocarriers for chemotherapeutic drugs, which can be bound to the capping ligand or directly to the AuNCs via different mechanisms. In this review, we present an overview of the diverse biomedical applications of AuNCs in terms of cancer imaging, therapy, and combinations thereof, as well as highlighting some additional applications relevant to biomedical research

Gold Nanoclusters: Imaging, Therapy, and Theranostic Roles in Biomedical Applications

For the past two decades, atomic gold nanoclusters (AuNCs, ultrasmall clusters of several to 100 gold atoms, having a total diameter of <2 nm) have emerged as promising agents in the diagnosis and treatment of cancer. Owing to their small size, significant quantization occurs to their conduction band, which leads to emergent photonic properties and the disappearance of the plasmonic responses observed in larger gold nanoparticles. For example, AuNCs exhibit native luminescent properties, which have been well-explored in the literature. Using proteins, peptides, or other biomolecules as structural scaffolds or capping ligands, required for the stabilization of AuNCs, improves their biocompatibility, while retaining their distinct optical properties. This paved the way for the use of AuNCs in fluorescent bioimaging, which later developed into multimodal imaging combined with computer tomography and magnetic resonance imaging as examples. The development of AuNC-based systems for diagnostic applications in cancer treatment was then made possible by employing active or passive tumor targeting strategies. Finally, the potential therapeutic applications of AuNCs are extensive, having been used as light-activated and radiotherapy agents, as well as nanocarriers for chemotherapeutic drugs, which can be bound to the capping ligand or directly to the AuNCs via different mechanisms. In this review, we present an overview of the diverse biomedical applications of AuNCs in terms of cancer imaging, therapy, and combinations thereof, as well as highlighting some additional applications relevant to biomedical research

Luminescent Gold Nanocluster-Decorated Polymeric Hybrid Particles with Assembly-Induced Emission

Ultrasmall gold atom clusters (<2 nm in diameter) or gold nanoclusters exhibit emergent photonic properties (near-infrared absorption and emission) compared to larger plasmonic gold particles because of the significant quantization of their conduction band. Although single gold nanocluster properties and applications are being increasingly investigated, little is still known about their behavior and properties when assembled into suprastructures, and even fewer studies are investigating their use for biomedical applications. Here, a simple synthetic pathway combines gold nanoclusters with thermosensitive diblock copolymers of poly(ethylene glycol) (PEG) and poly( N-isopropylacrylamide) (PNIPAm) to form a new class of gold-polymer, micelle-forming, hybrid nanoparticle. The nanohybrids' design is uniquely centered on enabling the temperature-dependent self-assembly of gold nanoclusters into the hydrophobic cores of micelles. This nonbulk assembly not only preserves but also enhances the attractive near-infrared photonics of the gold nanoclusters by significantly increasing their native fluorescent signal. In parallel to the fundamental insights into gold nanocluster ordering and assembly, the gold-polymer nanohybrids also demonstrated great potential as fluorescent live-imaging probes in vitro. This innovative material design based on the temperature-dependent, self-assembly of gold nanoclusters within a polymeric micelle's core shows great promise toward bioassays, nanosensors, and nanomedicine

Gold Nanoclusters: Imaging, Therapy, and Theranostic Roles in Biomedical Applications

For the past two decades, atomic gold nanoclusters (AuNCs, ultrasmall clusters of several to 100 gold atoms, having a total diameter of <2 nm) have emerged as promising agents in the diagnosis and treatment of cancer. Owing to their small size, significant quantization occurs to their conduction band, which leads to emergent photonic properties and the disappearance of the plasmonic responses observed in larger gold nanoparticles. For example, AuNCs exhibit native luminescent properties, which have been well-explored in the literature. Using proteins, peptides, or other biomolecules as structural scaffolds or capping ligands, required for the stabilization of AuNCs, improves their biocompatibility, while retaining their distinct optical properties. This paved the way for the use of AuNCs in fluorescent bioimaging, which later developed into multimodal imaging combined with computer tomography and magnetic resonance imaging as examples. The development of AuNC-based systems for diagnostic applications in cancer treatment was then made possible by employing active or passive tumor targeting strategies. Finally, the potential therapeutic applications of AuNCs are extensive, having been used as light-activated and radiotherapy agents, as well as nanocarriers for chemotherapeutic drugs, which can be bound to the capping ligand or directly to the AuNCs via different mechanisms. In this review, we present an overview of the diverse biomedical applications of AuNCs in terms of cancer imaging, therapy, and combinations thereof, as well as highlighting some additional applications relevant to biomedical research

Luminescent Gold Nanocluster-Decorated Polymeric Hybrid Particles with Assembly-Induced Emission

Ultrasmall gold atom clusters (<2 nm in diameter) or gold nanoclusters exhibit emergent photonic properties (near-infrared absorption and emission) compared to larger plasmonic gold particles because of the significant quantization of their conduction band. Although single gold nanocluster properties and applications are being increasingly investigated, little is still known about their behavior and properties when assembled into suprastructures, and even fewer studies are investigating their use for biomedical applications. Here, a simple synthetic pathway combines gold nanoclusters with thermosensitive diblock copolymers of poly(ethylene glycol) (PEG) and poly( N-isopropylacrylamide) (PNIPAm) to form a new class of gold-polymer, micelle-forming, hybrid nanoparticle. The nanohybrids' design is uniquely centered on enabling the temperature-dependent self-assembly of gold nanoclusters into the hydrophobic cores of micelles. This nonbulk assembly not only preserves but also enhances the attractive near-infrared photonics of the gold nanoclusters by significantly increasing their native fluorescent signal. In parallel to the fundamental insights into gold nanocluster ordering and assembly, the gold-polymer nanohybrids also demonstrated great potential as fluorescent live-imaging probes in vitro. This innovative material design based on the temperature-dependent, self-assembly of gold nanoclusters within a polymeric micelle's core shows great promise toward bioassays, nanosensors, and nanomedicine