Use of gold nanoparticle-silibinin conjugates: A novel approach against lung cancer cells

Abstract

Lung cancer presents one of the most challenging carcinomas with meager 5-year survival rates (less than 20%), high metastasis and high recurrence due to chemo- and radio- resistance. An alternative or complementation to existing prognosis modalities is the use of phytochemicals such as silibinin, which targets essential cytokines, angiogenic factors and transcription factors for a profound anti-tumor effect. However, the problems of low solubility in an aqueous physiological environment, poor penetration, high metabolism and rapid systemic clearance limit the therapeutic use of silibinin. Conjugation of gold nanoparticles (GNPs) with silibinin may overcome the above challenges along with distinct advantages of biocompatibility, optical properties for monitoring and causation of cytotoxicity in cancer cells. The current study thus aims to develop silibinin conjugated gold nanoparticles (Sb-GNPs) with pH responsive release in the cancer microenvironment, optimizing several parameters for its higher activity and further evaluate the nanoplatform for their efficacy in inducing cell death in vitro against A549 lung cancer cells. GNPs was synthesized using trisodium citrate dihydrate as the reducing agent and further used for the conjugation of silibinin. The synthesized GNPs were found to be monodispersed and spherical in shape. The silibinin was successfully conjugated with gold nanoparticles and long-term stability of GNPs and Sb-GNPs nanoconjugates in suspension phase was confirmed by FTIR and DLS. Anticancer properties of Sb-GNPs were confirmed by different assay using MTT, Trypan blue dye exclusion assay and cell cycle analysis assay. After conjugation of silibinin with GNPs, the efficacy of silibinin increased 4–5 times in killing the cancer cells. This is the first report on using silibinin gold nanoconjugate system for lung cancer therapy with promising future applications.

Inhalable Formulations to Treat Non-Small Cell Lung Cancer (NSCLC): Recent Therapies and Developments

“…ZnO-NPs have also been shown to cause tumor death, decrease drug resistance, and minimize side effects in vitro, when taken in combination with chemotherapeutics [ 135 ]. Umamaheswari et al used a green synthesis method for the production of ZnO nanoparticles [ 136 ]. Raphanus sativus var.…”

“…Yet, silibinin’s therapeutic use is limited by its low aqueous solubility, poor penetration, and increased metabolism leading to rapid systemic clearance. Hence, Ravi et al prepared silibinin-loaded gold nanoparticles (Sb-GNPs) using the Turkevich and Frens method with a citrate reducing agent and stirring the prepared gold nanoparticle with a silibinin solution [ 136 ]. GNPs synthesized were discovered to be monodispersed and spherical in shape.…”

“…Trypan blue dye exclusion assay showed that to produce a ~35–40% decrease in cell viability, a 5 μM dose of Sb-GNP was required in contrast to a 25 μM dose of free silibinin. Hence, it was concluded that conjugated silibinin was 4–5 times more efficacious than unconjugated [ 136 ].…”

Fabrication of Superparamagnetic Bimetallic Magnesium Nanoferrite Using Green Polyol: Characterization and Anticancer Analysis in Vitro on Lung Cancer Cell Line A549

“…based bimetallic nanoferrites have attracted interest among scientists and biotechnologists because of their versatile nature and useful applications . For instance, due to reasonably high electrical, thermal, chemical, and magnetic properties, the magnesium-based bimetallic magnetic nanoparticles have attracted much interest from biotechnologists. , They have exhibited promising applications in the area of engineering and biological sciences. , For example, magnesium ferrite has been used as a drug carrier in biocompatible hydrogels, with a general formula M +2 Fe 2 O 4 , along with their spinel structures, exhibiting good physical and chemical properties . The nanosized structure (within a range of 10–100 nm) induces interactions and accumulation within the cancerous tissues, which makes them a potential drug carrier that helps in their application in drug or gene delivery systems. , …”

“…16,17 They have exhibited promising applications in the area of engineering and biological sciences. 18,19 For example, magnesium ferrite has been used as a drug carrier in biocompatible hydrogels, with a general formula M +2 Fe 2 O 4 , along with their spinel structures, exhibiting good physical and chemical properties. 20 The nanosized structure (within a range of 10−100 nm) induces interactions and accumulation within the cancerous tissues, which makes them a potential drug carrier that helps in their application in drug or gene delivery systems.…”