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In the present investigation folate peptide (FA-Pep) conjugated 5-fluorouracil (5-FU) loaded nanoparticles were synthesized and their tumor targeting potentiality was monitored by different in vitro and in vivo techniques. FA-Pep-1 and FA-Pep-2 were synthesized and radiolabeled with (99m)Tc(CO)(3)(H(2)O)(3). (99m)Tc(CO)(3)-FA-Pep-1 exhibited promising tumor uptake in an in vivo model (nude mice bearing HeLa cell xenograft and Balb/c mice bearing B16F10 melanoma tumor) as compared to (99m)Tc(CO)(3)-FA-Pep-2. FA-Pep-1 was then conjugated with 5-FU-NPs (118 ± 4.3), as confirmed by the XPS study. These showed promising cytotoxic and apoptotic potential in B16F10 cell lines as compared to free 5-FU and unconjugated 5-FU-NPs. In vivo biodistribution and gamma-scintigraphy showed good accumulation of peptide conjugated NPs in the tumor region. Therapeutic efficacy studies in B16F10 tumor xenografts also exhibited substantial tumor growth inhibition. The above studies reveal that folate peptide conjugation may facilitate the tumor-targeting approach of 5-FU-NPs.

Curcumin (CUR), an antioxidant with p-glycoprotein inhibiting activity may be encapsulated with gemcitabine (GEM) as nanosuspension to enhance its anticancer potentiality synergistically. Folate conjugated single (CUR/GEM) and dual (CUR + GEM) drug-loaded nanoformulations were prepared and evaluated for P-glycoprotein-1 (pgy-1) gene resistance, followed by in vitro cellular uptake and cytotoxicity assay in cells. The in vivo biodistribution and scintigraphic imaging was done after radiolabeling the nanoparticles with 99mTechnetium (99mTc). The tumor inhibition study was conducted in nude mice bearing MDA-MB-231 xenografts. The folate conjugated dual drug formulations (FCGNPs) gave better results in suppressing the pgy-1 gene and also showed higher cellular uptake, cytotoxicity, apoptosis, and cell cycle arrest. The radiolabeled nanoformulations were highly stable and FCGNPs showed higher accumulation in the MDA-MB-231 tumor region than folate unconjugated dual drug NPs (CGNPs) as evidenced by scintigraphic imaging and biodistribution studies. The in vivo therapeutic efficacy of FCGNPs was higher compared to unconjugated and respective single-drug formulations. Two drugs in one platform lower breast adenocarcinoma by lowering drug resistance and improving cytotoxic effects.

Epigallocatechin-3-gallate (EGCG), a major polyphenolic constituent of green tea exhibits significant anti-cancer potential over a wide range of cancer cells. We have developed folate peptide decorated PLGA-NPs loaded with EGCG (FP-EGCG-NPs) to bind folate receptor (FR) specific breast cancer cell lines and evaluated their efficacy in pre-clinical studies. EGCG loaded PLGA nanoparticles (EGCG-NPs) were characterised for size, surface morphology, surface charge, encapsulation efficacy and in-vitro drug release kinetics. Cellular uptake and in-vitro cytotoxicities of free drug, folate peptide conjugated and unconjugated EGCG-NPs were investigated against FR positive MDA-MB-231 and MCF-7 cells. The conjugated nanoparticles exhibited promising cytotoxic potentials as well as significantly high cellular internalisation in MDA-MB-231 cells as compared to unconjugated one. It also ensured longer half life, higher plasma concentration, favourably high apoptotic potential and significantly high mitochondrial depolarization effect as compared to free EGCG. The loaded nanoparticles were radiolabeled with technetium-99m and their tumor selectivity in MDA-MB-231 tumor bearing nude mice was investigated by scintigraphic imaging study. Finally in-vivo therapeutic efficacy studies in tumor bearing nude mice were also done to evaluate the efficacy of the formulation for cancer treatment.

Green synthesis of metallic nanoparticles is a cost-effective environment-friendly technique and Quisqualis indica has ethnomedicinal values. With this background in this study, the floral extract of Q. indica was used to fabricate copper nanoparticles (QCuNPs) from copper acetate. Biophysical analysis revealed the formation of spherical, monodisperse, crystalline QCuNPs. Significant cytotoxic potentials of the nanoformulation were determined by MTT and lactate dehydrogenase (LDH) assay on B16F10 melanoma cells. Estimation of GSH and ROS demonstrated that QCuNPs induced melanoma cell death by induction of oxidative stress. Gene transcript analysis showed up-regulation of caspase-dependent as well as caspase-independent (AIF) apoptotic genes in treated cells. Comparative proteomics study mostly showed the abundance of apoptotic and cell cycle arrest proteins in treated samples. The in vivo therapeutic efficacy was studied in mice bearing B16F10 melanoma tumor where a significant decrease in tumor growth was observed in nanoparticles treated animal model. In conclusion, QCuNPs caused cytotoxicity and apoptosis in melanoma cells and its mechanism was established from gene expression and proteomic studies. QCuNPs exhibited potential suppression of B16F10 melanoma cell proliferation and substantial inhibition of tumor growth in animals. As per our information, this is the first study exploring the potential of Q. indica for the formulation of eco-friendly copper nanoparticle which will have great future application in the medicinal field.