Dataset Information

A multifunctional AIE gold cluster-based theranostic system: tumor-targeted imaging and Fenton reaction-assisted enhanced radiotherapy.

ABSTRACT:

Background

As cancer is one of the main leading causes of mortality, a series of monotherapies such as chemotherapy, gene therapy and radiotherapy have been developed to overcome this thorny problem. However, a single treatment approach could not achieve satisfactory effect in many experimental explorations.

Results

In this study, we report the fabrication of cyclic RGD peptide (cRGD) modified Au₄-iron oxide nanoparticle (Au₄-IO NP-cRGD) based on aggregation-induced emission (AIE) as a multifunctional theranostic system. Besides Au₄ cluster-based fluorescence imaging and enhanced radiotherapy, iron oxide (IO) nanocluster could realize magnetic resonance (MR) imaging and Fenton reaction-based chemotherapy. Abundant toxic reactive oxygen species generated from X-ray irradiation and in situ tumor-specific Fenton reaction under acidic microenvironment leads to the apoptotic and necrotic death of cancer cells. In vivo studies demonstrated good biocompatibility of Au₄-IO NP-cRGD and a high tumor suppression rate of 81.1% in the synergistic therapy group.

Conclusions

The successful dual-modal imaging and combined tumor therapy demonstrated AIE as a promising strategy for constructing multifunctional cancer theranostic platform.

SUBMITTER: Hua Y

PROVIDER: S-EPMC8686291 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Promoting processing efficiency and taking advantage of agricultural by-products are two promising ways to achieve sustainable textile industry. This study presents a customized efficient ultrasonic-assisted bleaching strategy for yak hair - a widely existing but underexploited secondary dark shade fibre from yak. A melanin-targeted Fenton oxidation process is established which involves three phases, i.e., (I) incorporation of Fe2+ ions with melanin, (II) catalytic oxidative bleaching using hydrogen peroxide (H2O2), and (III) reductive cleansing. The bleaching efficacy, dyeing performance and tensile property of yak hair treated with and without ultrasound were explored and compared. Further, the ultrasonic bleaching mechanism in terms of the catalytic effect of Fe2+ ions, the promotion of H2O2 decomposition, removal of melanin granule from yak hair, were demonstrated. Finally, the main effects and interactions of parameters in phase II, and optimal condition were obtained through mathematical modelling based on a central composite design (CCD). Results reveal that ultrasonic bleaching dramatically enhances the whiteness index (WI) of yak hair from 11 to 45 which is 44.6% higher than those bleached without ultrasound, and also promotes the uptake of acid dyes. There is only 15% tensile strength loss and 14% elongation increment of yak hair after ultrasonic bleaching, rising from a slight damage of cuticle layer and cleavage of disulfide bonds, respectively. In the study of bleaching mechanism, Fe2+ ion is confirmed to improve the H2O2 decomposition rate by 20.9% which further runs up to 35.9% after introducing ultrasound. Ultrasound increases the concentration of hydroxyl radicals (HO) by 94% which are the main oxidative species participating in bleaching confirmed by HO scavenging experiment. The porous structure was observed on the cross section of yak hair stemming from the removal of melanin granules contributed by the cleaning action of ultrasound. A theoretical highest WI of 52.4 can be achieved under an optimal condition based on the CCD study. In general, the proposed melanin-targeted bleaching strategy for yak hair that integrates ultrasonic technology and Fenton reaction, is beneficial to the development of sustainable textile industry from material and processing perspectives.

Project description:Two important features are required for promising radiosensitizers: one is selective tumor cell targeting to enhance the therapeutic outcome via lethal DNA damage and the other is rapid clearance to enable excellent biocompatibility for potential clinical application. Herein, ultrasmall gold nanoparticles (Au NPs) with diameter smaller than 5 nm were prepared and covered with a multifunctional peptide to endow them with selective tumor cell uptake capability. Combined with X-ray irradiation, the responsive Au NPs demonstrated superior radio-sensitizing toxicity and rapid renal clearance in vivo. Methods: A responsive peptide (Tat-R-EK) consists of three build blocks were used: a cell and even nuclear penetrating block derived from human immunodeficiency virus-1 transactivator of transcription protein (Tat), an cathepsin B cleavable linker, and a zwitterionic antifouling block. Ultrasmall Au NPs were prepared and then covered by the peptide via the Au-S bonds between gold and thiol groups from cysteine. The morphology, colloidal stability and the responsiveness of obtained Au@Tat-R-EK NPs were studied using transmittance electron microscopy and dynamic laser scattering. The selective cancer cell uptake and accumulation of Au@Tat-R-EK NPs in cancer tissue were studied via ICP-MS in vitro and in vivo, respectively. The cytotoxicity of Au@Tat-R-EK NPs on HepG2 cancer cells was evaluated in terms of cell viability, DNA damage, intracellular reactive oxygen species generation, and apoptosis analysis. Finally, the biocompatibility and tumor destruction ability against orthotopic LM3 liver cancers were verified in vivo. Results: Multifunctional peptide modified ultrasmall Au NPs were successfully prepared. The Au NPs exhibited enough colloidal stability and cathepsin B-responsive surface change, leading to selectively uptake by cancer cells in vitro and accumulation to tumor sites in vivo. Combined with X-ray irradiation, the responsive Au NPs demonstrated superior radio-sensitizing cytotoxicity in vitro and therapeutic outcome on mouse liver cancer in vivo. The ultrasmall size enables rapid clearance of the Au NPs, guarantees the biocompatibility in vivo for potential clinical applications. Conclusion: Some obstacles faced by the Au NPs-based radiotherapy, such as short circulation half-life, non-specific distribution, slow clearance and low radio-sensitizing effect, were effective solved through rational design of the smart nanomedicine. This work provides new insight in designing tumor microenvironment-responsive nanomedicine in cancer radiotherapy.