Silencing the Catalase Gene with SiRNA for Enhanced Chemodynamic Therapy

Abstract

Chemodynamic therapy (CDT) has been emerging as a promising strategy for cancer treatment. But the CDT efficiency is restricted by the insufficient intracellular hydrogen peroxide (H2O2) level. Herein, we present a method for H2O2 accumulation in tumor cells by silencing the catalase (CAT) gene with siRNA to achieve enhanced CDT. Cu-siRNA nanocomposites are fabricated by self-assembly of Cu2+ and CAT siRNA and then modified with hyaluronic acid (HA) for active tumor targeting. After tumor cell uptake, the released Cu2+ is reduced by highly expressed glutathione (GSH) to Cu+, which then catalyzes H2O2 to produce toxic hydroxyl radicals (•OH) to kill tumor cells. CAT siRNA can efficiently silence the CAT mRNA to inhibit the consumption of H2O2, resulting in H2O2 accumulation. The Cu2+-mediated GSH elimination and siRNA-induced endogenous H2O2 enrichment both potentiate CDT. Cu-siRNA@HA exhibits good biocompatibility and therapeutic efficiency. This work thus paves a new way to supply H2O2 in CDT and may hold potential for clinical application.

Pt‐Quantum‐Dot‐Modified Sulfur‐Doped NiFe Layered Double Hydroxide for High‐Current‐Density Alkaline Water Splitting at Industrial Temperature

“…Notably, the electrochemical performance of Pt@S–NiFe LDH is not only superior to that of 40% Pt/C but the corresponding overpotential at 10 mA cm −2 and Tafel slope of Pt@S–NiFe LDH are also significantly lower than those of recently reported state‐of‐the‐art HER electrocatalysts (Figure 2e). [ 24–34 ]…”

Inorganic nanoparticle agents for enhanced chemodynamic therapy of tumours

“…77 A recent study employed small interfering RNAs (siRNAs) to silence the CAT gene, aiming to reduce the CAT expression. 78 Specifically, nanocomposite particles were constructed by selfassembling Cu 2+ and CAT-silencing siRNAs, followed by modification with hyaluronic acid (HA) for tumour targeting. After tumoural uptake, the nanoparticles were able to elevate the intracellular level of H 2 O 2 , and intensify the oxidative stress in tumour cells as intended.…”

Dual Active Sites Engineering on Sea Urchin‐Like CoNiS Hollow Nanosphere for Stabilizing Oxygen Electrocatalysis via a Template‐Free Vulcanization Strategy

“…[ 13,14 ] In addition, many studies have proved that the introduction of transition metal sulfide to the carbon skeleton can effectively adjust the electronic structure of carbon (with defects) to improve the electrochemical performance. [ 15–20 ] Based on these principles, Wei et al. synthesize graded C/NiCo 2 S 4 nanospheres by a template‐assisted hydrothermal method.…”