Zebrafish Cancer Avatars: A Translational Platform for Analyzing Tumor Heterogeneity and Predicting Patient Outcomes

The increasing number of available anti-cancer drugs presents a challenge for oncologists, who must choose the most effective treatment for the patient. Precision cancer medicine relies on matching a drug with a tumor’s molecular profile to optimize the therapeutic benefit. However, current precision medicine approaches do not fully account for intra-tumoral heterogeneity. Different mutation profiles and cell behaviors within a single heterogeneous tumor can significantly impact therapy response and patient outcomes. Patient-derived avatar models recapitulate a patient’s tumor in an animal or dish and provide the means to functionally assess heterogeneity’s impact on drug response. Mouse xenograft and organoid avatars are well-established, but the time required to generate these models is not practical for clinical decision-making. Zebrafish are emerging as a time-efficient and cost-effective cancer avatar model. In this review, we highlight recent developments in zebrafish cancer avatar models and discuss the unique features of zebrafish that make them ideal for the interrogation of cancer heterogeneity and as part of precision cancer medicine pipelines

Zebrafish Cancer Avatars: A Translational Platform for Analyzing Tumor Heterogeneity and Predicting Patient Outcomes

The increasing number of available anti-cancer drugs presents a challenge for oncologists, who must choose the most effective treatment for the patient. Precision cancer medicine relies on matching a drug with a tumor’s molecular profile to optimize the therapeutic benefit. However, current precision medicine approaches do not fully account for intra-tumoral heterogeneity. Different mutation profiles and cell behaviors within a single heterogeneous tumor can significantly impact therapy response and patient outcomes. Patient-derived avatar models recapitulate a patient’s tumor in an animal or dish and provide the means to functionally assess heterogeneity’s impact on drug response. Mouse xenograft and organoid avatars are well-established, but the time required to generate these models is not practical for clinical decision-making. Zebrafish are emerging as a time-efficient and cost-effective cancer avatar model. In this review, we highlight recent developments in zebrafish cancer avatar models and discuss the unique features of zebrafish that make them ideal for the interrogation of cancer heterogeneity and as part of precision cancer medicine pipelines

Phase Transfer of Citrate Stabilized Gold Nanoparticles Using Nonspecifically Adsorbed Polymers

Many synthetic approaches for gold nanoparticles rely on an aqueous media, resulting in water-soluble nanoparticles, which limits the ability to incorporate gold nanoparticles into other organic solvents or hydrophobic polymeric composites. Surface functionalization and phase transfer approaches using alkylthiols or alkylamines, which strongly bind the gold surface, are common routes to overcome this limitation, however they are typically challenging methods. In this paper we report an approach to transport citrate capped gold nanoparticles into a variety of solvents, including ones that are hydrophobic and not miscible with water without the need for phase transfer agents. We suspend gold nanoparticles in a water-miscible polar organic solvent that also is a solvent for a hydrophobic polymer. After drying, polymer-stabilized gold nanoparticles were found to be dispersible in various hydrophobic solvents with maintained colloidal stability. This work investigates two hydrophobic polymers, namely (polymethylmethacrylate and polyvinylacetate), which share common chemical motifs but have significantly different physiochemical properties. Interestingly, a significant difference in their ability to stabilize the transferred gold nanoparticles is observed and discussed

Colloidal Stability of Citrate and Mercaptoacetic Acid Capped Gold Nanoparticles upon Lyophilization: Effect of Capping Ligand Attachment and Type of Cryoprotectants

For various applications of gold nanotechnology, long-term nanoparticle stability in solution is a major challenge. Lyophilization (freeze–drying) is a widely used process to convert labile protein and various colloidal systems into powder for improved long-term stability. However, the lyophilization process itself may induce various stresses resulting in nanoparticle aggregation. Despite a plethora of studies evaluating lyophilization of proteins, liposomes, and polymeric nanoparticles, little is known about the stability of gold nanoparticles (GNPs) upon lyophilization. Herein, the effects of lyophilization and freeze–thaw cycles on the stability of two types of GNPs: Citrate-capped GNPs (stabilized via weakly physisorbed citrate ions, Cit-GNPs) and mercaptoacetic acid-capped GNPs (stabilized via strongly chemisorbed mercaptoacetic acid, MAA-GNPs) are investigated. Both types of GNPs have similar core size and effective surface charge as evident from transmission electron microscopy and zeta potential measurements, respectively. Plasmon absorption of GNPs and its dependence on nanoparticle aggregation was employed to follow stability of GNPs in combination with dynamic light scattering analysis. Plasmon peak broadening index (PPBI) is proposed herein for the first time to quantify GNPs aggregation using nonlinear Gaussian fitting of GNPs UV–vis spectra. Our results indicate that Cit-GNPs aggregate irreversibly upon freeze–thaw cycles and lyophilization. In contrast, MAA-GNPs exhibits remarkable stability under the same conditions. Cit-GNPs exhibit no significant aggregation in the presence of cryoprotectants (molecules that are typically used to protect labile ingredients during lyophilization) upon freeze–thaw cycles and lyophilization. The effectiveness of the cyroprotectants evaluated was on the order of trehalose or sucrose > sorbitol > mannitol. The ability of cryoprotectants to prevent GNPs aggregation was dependent on their chemical structure and their ability to interact with the GNPs as assessed with zeta potential analysis

Colloidal Stability of Citrate and Mercaptoacetic Acid Capped Gold Nanoparticles upon Lyophilization: Effect of Capping Ligand Attachment and Type of Cryoprotectants

For various applications of gold nanotechnology, long-term nanoparticle stability in solution is a major challenge. Lyophilization (freeze–drying) is a widely used process to convert labile protein and various colloidal systems into powder for improved long-term stability. However, the lyophilization process itself may induce various stresses resulting in nanoparticle aggregation. Despite a plethora of studies evaluating lyophilization of proteins, liposomes, and polymeric nanoparticles, little is known about the stability of gold nanoparticles (GNPs) upon lyophilization. Herein, the effects of lyophilization and freeze–thaw cycles on the stability of two types of GNPs: Citrate-capped GNPs (stabilized via weakly physisorbed citrate ions, Cit-GNPs) and mercaptoacetic acid-capped GNPs (stabilized via strongly chemisorbed mercaptoacetic acid, MAA-GNPs) are investigated. Both types of GNPs have similar core size and effective surface charge as evident from transmission electron microscopy and zeta potential measurements, respectively. Plasmon absorption of GNPs and its dependence on nanoparticle aggregation was employed to follow stability of GNPs in combination with dynamic light scattering analysis. Plasmon peak broadening index (PPBI) is proposed herein for the first time to quantify GNPs aggregation using nonlinear Gaussian fitting of GNPs UV–vis spectra. Our results indicate that Cit-GNPs aggregate irreversibly upon freeze–thaw cycles and lyophilization. In contrast, MAA-GNPs exhibits remarkable stability under the same conditions. Cit-GNPs exhibit no significant aggregation in the presence of cryoprotectants (molecules that are typically used to protect labile ingredients during lyophilization) upon freeze–thaw cycles and lyophilization. The effectiveness of the cyroprotectants evaluated was on the order of trehalose or sucrose > sorbitol > mannitol. The ability of cryoprotectants to prevent GNPs aggregation was dependent on their chemical structure and their ability to interact with the GNPs as assessed with zeta potential analysis