Exploring the cytotoxicity on human lung cancer cells and DNA binding stratagem of camptothecin functionalised silver nanoparticles through multi-spectroscopic, and calorimetric approach

Abstract

The influence of nanoparticles inside the human body and their interactions with biological macromolecules need to be explored/studied prior to specific applications. The objective of this study is to find the potential of camptothecin functionalised silver nanoparticles (CMT-AgNPs) in biomedical applications. This article primarily investigates the binding stratagem of CMT-AgNPs with calf thymus DNA (ctDNA) through a series of spectroscopic and calorimetric methods and then analyses the anticancer activity and cytotoxicity of CMT-AgNPs. The nanoparticles were synthesized using a simple one pot method and characterized using UV–Visible, fourier transform infrared (FTIR) spectroscopy, X-ray diffraction and high-resolution transmission electron microscopy (HRTEM). The average size of CMT-AgNPs is 10 ± 2 nm. A group of experimental techniques such as UV–Visible spectrophotometry, fluorescence dye displacement assay, circular dichroism (CD) and viscosity analysis unravelled the typical groove binding mode of CMT-AgNPs with ctDNA. The CD measurement evidenced the minor conformational alterations of double helical structure of ctDNA in the presence of CMT-AgNPs. The information deduced from the isothermal titration calorimetry (ITC) experiment is that the binding was exothermic and spontaneous in nature. Moreover, all the thermodynamic binding parameters were extracted from the ITC data. The binding constants obtained from UV absorption experiments, fluorescence dye displacement studies and ITC were consistently in the order of 104 Mol−1. All these results validated the formation of CMT-AgNPs–ctDNA complex and the results unambiguously confirm the typical groove binding mode of CMT-AgNPs. An exhaustive in vitro MTT assay by CMT-AgNPs and CMT against A549, HT29, HeLa and L929 cell lines revealed the capability of CMT-AgNPs as a potential anticancer agent.

Dynamic 3D in vitro lung models: applications of inorganic nanoparticles for model development and characterization

“…As previously mentioned, the majority of research regarding NPs in the context of in vitro lung models is in relation to their toxicity or potential as therapeutics. 178–181 While the use of NPs as contrast agents is quite common in in vivo studies, 182–184 few studies recognize their utility as agents to characterize and functionalize lung in vitro 3D models. Characterizing these models and evaluating the effect of different therapeutics is particularly challenging given their complex architecture, which can pose penetration depth limits and hamper the diffusion of labels, antibodies or dyes, and the ability to follow their evolution over time.…”

The development of nanocarriers for natural products

“…Camptothecin [CPT, (4S)-4-Ethyl-4-hydroxy-1H-pyrano[3 0 ,4 0 :6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione], an indole alkaloid characterized by a pentacyclic structure, is primarily derived from Camptotheca acuminata (Schultz, 1973). Several studies have shown that CPT and its derivatives can inhibit the progression of malignancies, including breast, cervical, lung, and liver cancers (Ali et al, 2023;Hou et al, 2023;Raj et al, 2023). Mechanistic investigations have elucidated that CPT forms covalent complexes with topoisomerase I (TOPO I) and DNA, thereby inhibiting DNA re-ligation, leading to DNA strand breaks, and consequently inducing apoptosis, which are promising features of cancer therapeutics (Tesauro et al, 2019;Thomas & Pommier, 2019).…”

Rosmarinic Acid-Rich Perilla frutescens Extract-Derived Silver Nanoparticles: A Green Synthesis Approach for Multifunctional Biomedical Applications including Antibacterial, Antioxidant, and Anticancer Activities

“…AgNPs have shown promise as potential anticancer agents due to their ability to induce apoptosis (cell death) in cancer cells. Additionally, AgNPs have been shown to have low toxicity towards normal cells, making them a potential alternative to conventional chemotherapy drugs [ 21 , 22 , 23 ]. AgNPs have been investigated as potential drug delivery vehicles due to their small size and unique physicochemical properties.…”