br The change in tumour volume was also observed
The change in tumour volume was also observed and results re-vealed that the tumour growth was inhibited in the mice receiving the EGCG formulations (Fig. 9). The percent increase in tumour volume in mice treated with EGCG-SLN and EB-SLN was 3.78% and 0.78%, re-spectively, as compared to mice receiving pure EGCG and the control group which were 5.45% and 7.97%, respectively.
In this work, we prepared bombesin conjugated, EGCG loaded solid lipid nanoparticles by the double-emulsification solvent evaporation
method followed by conjugation using EDC–NHS reaction. FTIR ana-lysis validated the formation of the amide bond between the carboxylic C–O group of the lipid with the free amine group of the peptide. Antitumor eﬀects of EB-SLN are shown by MTT assay, cell morphology and apoptosis induction. Targeted formulations show enhanced cyto-toxicity, higher cellular uptake, increased apoptosis and better control over cell migration compared to non-targeted formulations. In-vivo tu-mour activity of nanoparticles are shown in syngeneic mouse model. Targeted nanoparticles show better control over tumour growth and enhanced survivability. These findings suggest that conjugation of BBN as a targeting ligand to the EGCG-encapsulated SLN system, further corroborating the potential of EGCG-encapsulated systems in cancer therapeutics.
Authors are grateful to the Director, Indian Institute of Chemical Technology, Hyderabad for providing the necessary facilities and sup-port. R.R. thanks RMIT-IICT Research centre, Hyderabad for providing the resources and fellowship to carry out the study. D.P. thanks RMIT-IICT Research Centre, Hyderabad for providing a Research Associate fellowship. H.K. acknowledges the Department of Science and Technology, New Delhi for awarding DST INSPIRE Faculty Award. This
R. Radhakrishnan, et al. Chemistry and Physics of Lipids xxx (xxxx) xxx–xxx
Fig. 6. Scratch assay images for MDA-MB-231 human breast cancer SCR 7 after 0 h (A) and 24 h (B) of treatment with blank solid lipid nanoparticles (blank SLN), pure epigallocatechin gallate (EGCG), EGCG-loaded SLN (EGCG-SLN) and bombesin conjugated SLN (EB-SLN) equivalent to 20 μg/mL EGCG, along with control cells for reference.
Fig. 7. Kaplan-Meier plot for survival following administration of pure epi-gallocatechin gallate (EGCG), EGCG-loaded SLN (EGCG-SLN) and bombesin conjugated SLN (EB-SLN) formulations, with control mice for reference.
Fig. 9. Change in tumour volume in mice with the number of days following administration of pure epigallocatechin gallate (EGCG), EGCG-loaded SLN (EGCG-SLN) and bombesin conjugated SLN (EB-SLN) formulations with control mice for reference.
Fig. 8. Change in body weight in mice with the number of days following ad-ministration of pure epigallocatechin gallate (EGCG), EGCG-loaded SLN (EGCG-SLN) and bombesin conjugated SLN (EB-SLN) formulations with control mice for reference.
work was financially supported by CSIR grant under project Advanced Drug Delivery (ADDCSC 0302).
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9 Original Article
Bone Marrow Mesenchymal Stem Cell-Derived Exosomal MicroRNA-126-3p Inhibits Pancreatic Cancer Development by Targeting ADAM9
1Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou 221116, China; 2College of Health Sciences, Jiangsu Normal University, Xuzhou 221116, Jiangsu, China; 3State Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, Jiangsu, China
Pancreatic cancer is a lethal malignancy with relatively few effective therapies. Recent investigations have highlighted the role of microRNAs (miRNAs) as crucial regulators in various tumor processes including tumor progression. Hence the cur-rent study aimed to investigate the role of bone marrow mesen-chymal stem cell (BMSC)-derived exosomal microRNA-126-3p (miR-126-3p) in pancreatic cancer. Initially, miRNA candi-dates and related genes associated with pancreatic cancer were screened. PANC-1 cells were transfected with miR-126-3p or silenced a disintegrin and a metalloproteinase-9 (ADAM9) to examine their regulatory roles in pancreatic can-cer cells. Additionally, exosomes derived from BMSCs were iso-lated and co-cultured with pancreatic cancer cells to elucidate the effects of exosomes in pancreatic cancer. Furthermore, the effects of overexpressed miR-126-3p derived from BMSCs exosomes on proliferation, migration, invasion, apoptosis, tu-mor growth, and metastasis of pancreatic cancer cells were analyzed in connection with lentiviral packaged miR-126-3p in vivo. Restored miR-126-3p was observed to suppress pancre-atic cancer through downregulating ADAM9. Notably, overex-pressed miR-126-3p derived from BMSCs exosomes inhibited the proliferation, invasion, and metastasis of pancreatic cancer cells, and promoted their apoptosis both in vitro and in vivo. Taken together, the key findings of the study indicated that overexpressed miR-126-3p derived from BMSCs exosomes inhibited the development of pancreatic cancer through the downregulation of ADAM9, highlighting the potential of miR-126-3p as a novel biomarker for pancreatic cancer treatment.