Ruthenium-loaded mesoporous silica as tumor microenvironment-response nano-fenton reactors for precise cancer therapy

Abstract

Background Nano-Fenton reactors as novel strategy to selectively convert hydrogen peroxide (H2O2) into active hydroxyl radicals in tumor microenvironment for cancer therapy had attracted much attention. However, side effects and low efficiency remain the main drawbacks for cancer precise therapy. Results Here, ruthenium-loaded palmitoyl ascorbate (PA)-modified mesoporous silica (Ru@SiO2-PA) was successfully fabricated and characterized. The results indicated that Ru@SiO2-PA under pH6.0 environment displayed enhanced growth inhibition against human cancer cells than that of pH7.4, which indicated the super selectivity between cancer cells and normal cells. Ru@SiO2-PA also induced enhanced cancer cells apoptosis, followed by caspase-3 activation and cytochrome-c release. Mechanism investigation revealed that Ru@SiO2-PA caused enhanced generation of superoxide anion, which subsequently triggered DNA damage and dysfunction of MAPKs and PI3K/AKT pathways. Moreover, Ru@SiO2-PA effectively inhibited tumor spheroids and tumor xenografts growth in vivo by induction of apoptosis. The real-time imaging by monitoring Ru fluorescence in vitro and in vivo revealed that Ru@SiO2-PA mainly accumulated in cell nucleus and tumor xenografts. Importantly, Ru@SiO2-PA showed no side effects in vivo, predicting the safety and potential application in clinic. Conclusions Our findings validated the rational design that Ru@SiO2-PA can act as novel tumor microenvironment-response nano-Fenton reactors for cancer precise therapy. Graphic Abstract

RGD Peptide-Conjugated Selenium Nanocomposite Inhibits Human Glioma Growth by Triggering Mitochondrial Dysfunction and ROS-Dependent MAPKs Activation

“…MAPKs pathway can regulate cell growth, cell proliferation and cell division, which plays key role in drugs-induced apoptosis in human cancers ( Sun et al, 2020 ; Sun et al, 2021 ). Herein, the three main components of MAPKs pathway, JNK, ERK and p38, were all examined to explore the underlying anticancer mechanism induced by Ag@Se@RGD NPs in U251 cells.…”

“…Glioma is still considered as the most common primary malignant brain tumors, accounting for about 80% of malignant brain tumors ( Gittleman et al, 2020 ). Chemotherapy as one of the most commonly used cancer treatments is severely affected by drug dosage and drug toxicity ( Deng et al, 2015 ; Sun et al, 2021 ). The prognosis of gliomas is often poor, and chemotherapy resistance remains the challenge in therapy of human glioma ( da Silva., et al, 2020 ; Ding et al, 2020 ; Guo et al, 2021 ).…”

Tumor microenvironment-responsive fenton nanocatalysts for intensified anticancer treatment

“…In addition to Fe-and Mn-based Fenton reagents, other metals have also been used to catalyze Fenton-like reactions, such as Ti [ 51 ], Cu [ 52 ], Ag [ 53 ], V [ 54 ], Pt [ 55 ], Co [ 56 ], Ru [ 57 ] and Au [ 58 ], etc. For Cu-based NCs, the MOF derivatives of Cu [ 59 ], sulfides of Cu (such as CuS [ 60 ] and Cu 2-x S [ 61 ]), copper oxides (such as CuO [ 62 , 63 ] and Cu 2 O [ 64 ]), and copper bimetallic compounds (such as CuSe) [ 65 ], are used as catalysts of Fenton-like reactions.…”

Are smart delivery systems the solution to overcome the lack of selectivity of current metallodrugs in cancer therapy?

“…100 Fan et al also developed a novel smart nanoplatform as a nano-Fenton reactor for the simultaneous therapy and imaging of cancer. 101 The authors modified mesoporous silica nanoparticles (140 nm) with the antioxidant palmitoyl ascorbate and loaded them (31%) with the luminescent complex [Ru(bipy) 3 ] 2+ (bipy = 2,2′ bipyridine) to achieve the desired nanoplatform. In vitro, the loaded nanoparticles exhibited pH-dependent drug release with selective cytotoxicity for HepG2 liver, MCF-7 breast, and SGC-7901 stomach cancer cells at pH 6.0 over pH 7.4.…”

“…Altogether, the results seem to predict the safety and potential application in clinics according to the authors. 101 The pH-triggered release of ruthenium organometallic complexes from tumour-targeting delivery nanosystems into the cancer site has been equally described. Knežević and coworkers reported the passive delivery of [Ru(η 6 -p-cym)(TMH) Cl 2 ] (H1[Ru]) or [Ru(η 6 -p-cym)(DTPH)Cl 2 ] (H2 [Ru], where TMH = (2-thienylmethyl)hydrazine; DTPH = (5,6-dimethylthieno[2,3d]pyrimidin-4-yl)hydrazine) upon exposure to the tumour's acidic conditions.…”