ABSTRACT
Cisplatin is a chemotherapeutic agent used for treating various malignancies. The study aimed to prepare pegylated liposomal cisplatin and evaluate its efficacy against human breast cancer cell line MCF-7. Drug-loaded nanoparticles were synthesized by reverse phase evaporation technique. The study is highlighted by extensive characterization of nanoparticles in terms of nanoparticle morphology, type of drug entrapment, cisplatin retention capability, and cytotoxicity effects. The size, size distribution, and zeta potential of nanodrug were estimated 142 nm, 0.33, and -22 mV, respectively. Drug-loading efficiency was equal to 48% that occurred physically. Furthermore, high retention capability (39% of drug was released after 72 h) with significantly enhanced cytotoxicity of nanodrug (1.75 times more than the standard drug) confirmed the potency of liposomal nanoparticles as proper cisplatin carrier.
Subject(s)
Cell Survival/drug effects , Cisplatin/chemistry , Cisplatin/toxicity , Liposomes/chemistry , Nanoparticles/chemistry , Nanoparticles/toxicity , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/toxicity , Cell Line, Tumor , Cisplatin/pharmacology , Humans , Microscopy, Atomic Force , Particle SizeABSTRACT
Apoptosis is a naturally occurring process by which a cell is directed to programmed cell death. Chemotherapy drugs affect the cancer cells by the apoptotic induction. During the present study, a series of 4H-chromene-3-carbonitrile was synthesized by one-pot method as the inducers of apoptosis. Cytotoxic effects of six compounds of 4H-chromene-3-carbonitrile were evaluated against five tumor cell lines, with the help of colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Compound 4 showed significant cytotoxic activity and was selected for conjugation with the synthesized gold nanoparticles by aspartic acid. Also, we evaluated apoptosis induction capacity of the selected compound with the help of fluorescent dyes and DNA fragmentation. The result showed that the conjugated and non-conjugated forms of compound 4 were effective in inducing apoptosis and conjugated one had more efficiency and reduced the effective dose. Also, molecular modeling experiments involving compound 4 and colchicine binding site of tubulin dimer showed several strong hydrogen bonds and hydrophobic interactions to many important amino acid residues and GTP.
