Scalable Yielding of Highly Stable Polyelectrolyte‐Coated Copper Sulfide Nanoparticles by Flash Nanoprecipitation for Photothermal‐Chemotherapeutics

Abstract

Photothermal‐chemotherapeutic nanoparticles (NPs) are attracting increasing attention and becoming more widely used for cancer therapy in the clinic due to their noninvasiveness, notable tissue penetration abilities, and low systemic adverse effects. However, functional ligands are conventionally modified onto photothermal NPs to well stabilize the inorganic particles suffering from complex chemical modifications, low productivity, and batch‐to‐batch inconsistencies, and thus significantly restricting their clinical applications. Herein, flash nanoprecipitation (FNP) is taken advantage of to afford rapid and uniform mixing for generating local supersaturated CuS clusters for small and highly stable CuS NPs effectively stabilized by polyacrylic acid through a continuous strategy. It greatly reduces the complexity for CuS NPs synthesis and functionalization in a facile intensified mixing process. These as‐synthesized particles are high‐drug loading, scalable, and most importantly, it is easy to control their sizes and charges through external conditions. Toxicity and tumor inhibition experiments confirm the high cell toxicity and good suppression of tumor growth under near‐infrared irradiation indicating a promising prospect of FNP in the large‐scale and continuous yielding of highly stable and high‐performing photothermal‐chemotherapeutic NPs for cancer therapy.

Engineered Polymer-Supported Biorthogonal Nanocatalysts Using Flash Nanoprecipitation

“…The solvent/antisolvent ratio was chosen as an essential parameter during FNP due to its ability to regulate the supersaturation conditions . For the hydrophobic Pd catalyst molecule, a low organic solvent content reduced its solubility and therefore created a high supersaturation level.…”

“…The solvent/antisolvent ratio was chosen as an essential parameter during FNP due to its ability to regulate the supersaturation conditions. 37 For the hydrophobic Pd catalyst molecule, a low organic solvent content reduced its solubility and therefore created a high supersaturation level. As mentioned before (3.2.1), a higher supersaturation level led to the faster nucleation and growth rate before the catalyst molecules were stabilized by the polymer.…”

“…Flash nanoprecipitation (FNP) is an efficient nanoparticle fabrication process that uses engineered mixing geometries to stabilize insoluble compounds into nanosized polymer-based delivery vehicles. − The high flow rate of two impingent streams enables microsecond mixing and creates supersaturation conditions, generating nanoparticles with narrow size distribution and high loading capacity. , In this technique, stabilizing polymers are usually designed to have hydrophobic segments that encapsulate solute particles as well as hydrophilic segments that provide steric stabilization. In this study, we encapsulated a palladium-based TMC, Pd­(dppf)­Cl 2 , into polymeric nanoparticles via FNP for efficient bioorthogonal catalysis in biological environments (Figure a).…”

Biodegradable Porous Polymeric Drug with pH-Stimuli-Responsive Delivery Capacity for Combined Cancer Therapy

“…To further quantify drug and nanoparticle accumulation, the levels of DOX in tumors and organs were evaluated using an in vivo NIR fluorescence imaging system. Due to the strong fluorescence interference of mouse skin, 60 the treated mice were euthanized, and ex vivo fluorescence signals were observed in the tumors after intraperitoneal injection. As depicted in Figure 5c and Figure S17, fluorescence signals became increasingly strong with time at an amazing rate.…”

Biomimetic Polymer-Templated Copper Nanoparticles Stabilize a Temozolomide Intermediate for Chemotherapy against Glioblastoma Multiforme

“…Copper is a necessary cofactor for various metabolic enzymes and participates in numerous physiological and pathological processes . The use of copper for cancer treatment has been widely reported, such as chemodynamic therapy (CDT), photothermal therapy, , and copper chelators . In CDT, the hydroxyl radical ( • OH), the highly toxic reactive oxygen species (ROS), is available via the Fenton reaction for cancer treatment and can circumvent the obstacles of tissue depth and hypoxia-associated resistance effectively. − Fe 2+ is often used to generate • OH.…”