Supercritical Fluid-Assisted Fabrication of Indocyanine Green-Encapsulated Silk Fibroin Nanoparticles for Dual-Triggered Cancer Therapy

Abstract

Despite the success and advantages over traditional chemotherapeutic strategies, photothermal therapy (PTT) suffers from certain limitations, such as poor stability, low therapeutic efficacy of PTT agents in vivo, and their affinity loss during the multistep synthesis process of delivery carriers, among others. To address these limitations, we designed a stable, biocompatible, and dual-triggered formulation of indocyanine green (ICG)-encapsulated silk fibroin (SF) (ICG-SF) nanoparticles using supercritical fluid (SCF) technology. We demonstrated that ICG encapsulation in SF through this environmental-friendly approach has offered excellent photothermal stability, the pH-responsive release of ICG from SF specifically in the tumor acidic environment, and its substantial activation with near-infrared (NIR) light at 808 nm significantly enhanced the PTT efficiency. In vitro and in vivo photothermal experiments have shown that these ICG-SF nanoparticles were capable of devastating tumor cells merely under light-induced hyperthermia. Together, these results have suggested that the biocompatible ICG-SF nanoparticles prepared by the SCF process resulted in high PTT efficiency and may have a great potential as a delivery system for sustained cancer therapy.

Engineered pH‐responsive hydrazone‐carboxylate complexes‐encapsulated 2D matrices for cathepsin‐mediated apoptosis in cancer

“…Along this line, numerous inorganic nanoconstructs based on gold, silver, platinum, silica, calcium phosphates, and selenium, phosphorous as well as tellurium‐based quantum dots, have been engineered for diverse applications . Despite their significant advancements, stability and success in the delivery of therapeutic cargo, these inorganic systems‐based biomaterials suffer from a significant challenge of low degradation rate in the biological environment, which then, leading to the long‐term accumulation‐induced biosafety risk in the cells …”

“…Among the various external stimuli, pH of the surrounding microenvironment is the most efficient biological stimuli in delivering chemotherapeutic agents . Moreover, it is highly convenient to fabricate such controlled delivery systems as the tumors hold lower pH of ~4.5–6.0 compared to that of the neighboring physiological fluids (pH 7.4) . Often times, the internalized nanocarriers in the tumor cells are engulfed by the endosomes or lysosomes, that are with mildly acidic microenvironment, which significantly results in the intracellular delivery of the therapeutic cargo .…”

“…Moreover, it is highly convenient to fabricate such controlled delivery systems as the tumors hold lower pH of ~4.5–6.0 compared to that of the neighboring physiological fluids (pH 7.4) . Often times, the internalized nanocarriers in the tumor cells are engulfed by the endosomes or lysosomes, that are with mildly acidic microenvironment, which significantly results in the intracellular delivery of the therapeutic cargo . Furthermore, the utilization of LDH for enclosing these complexes is advantageous as the surface hydroxyl groups of these 2D LDH matrices were protonated and result in the weakening of the interactions within the layers leading to their breakdown, which also facilitate the release of the complexes in the acidic environment …”

“…In an effort to achieve the fabrication of pH‐sensitive molecular design with significant therapeutic efficacy, we fabricated the pH‐sensitive hydrazone complexes (Fig. ) of Dox molecules facilitating their specific release of Dox in the acidic microenvironment of tumor . On the other hand, the 2D LDH matrices were prepared by the hydrothermal‐assisted co‐precipitation of Mg and Al salts in the alkaline conditions .…”

“…[6][7][8] Despite their significant advancements, stability and success in the delivery of therapeutic cargo, these inorganic systems-based biomaterials suffer from a significant challenge of low degradation rate in the biological environment, which then, leading to the long-term accumulation-induced biosafety risk in the cells. 9,10 Herein, layered double hydroxides (LDHs), two-dimensional (2D) material, have garnered much interest from researchers toward biomedicine on account of their attractive properties such as biocompatibility, biodegradability, unique physical and chemical attributes, and exceptional expanding properties due to weak interlayer bonding, among others. 11,12 LDH nanoparticles are the biodegradable anionic clays that are fabricated using various di-and trivalent cations by changing the molar ratio of M 3+ /M 2+ coordinated with functional hydroxides.…”