TY - JOUR
T1 - Improved cisplatin delivery in cervical cancer cells by utilizing folate-grafted non-aggregated gelatin nanoparticles
AU - Dixit, Nishu
AU - Vaibhav, Kumar
AU - Pandey, Ravi Shankar
AU - Jain, Upendra Kumar
AU - Katare, Om Prakash
AU - Katyal, Anju
AU - Madan, Jitender
N1 - Publisher Copyright:
© 2014 Elsevier Masson SAS.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - Purpose: Cisplatin is highly effective in the treatment of cervical cancer. However, in therapeutic doses, cisplatin induces several adverse effects due to undesirable tissue distribution. Therefore, it is worth targeting cisplatin in cervical cancer cells by implicating non-aggregated ligand-modified nanotherapeutics. Methods and results: Here, we report the preparation of non-aggregated folic acid-conjugated gelatin nanoparticles of cisplatin (Cis-GNs-FA) by two-step desolvation method with mean particle size of 210.6±9.6nm and 140.5±10.9nm for Cis-GNs to improve the drug delivery in cervical cancer, HeLa cells. FTIR and DSC spectra confirmed the presence and stability of cisplatin in gelatin matrix. Furthermore, amorphization of cisplatin in nanoparticles was ascertained by PXRD. Drug release followed a first-order release kinetic at both pH~5.6 (cervical cancer pH) and pH~7.4. In addition, a significant (P<0.05) decrease in IC50 value (8.3μM) and enhanced apoptosis were observed in HeLa cells treated with Cis-GNs-FA as compared to Cis-GNs (15.1μM) and cisplatin solution (40.2μM). In contrast, A549 lung cancer cells did not discriminate between Cis-GNs-FA and Cis-GNs due to the absence of folate receptors-α (FR-α). Consistently, higher cellular uptake, 80.54±7.60% was promoted by Cis-GNs-FA significantly (two-way ANOVA, P<0.05) greater than 51.68±9.78%, by Cis-GNs. This was also illustrated by CLSM images, which indicated that Cis-GNs-FA preferably accumulated in the cytoplasm of HeLa cells nearby nucleus by following receptor-mediated endocytosis pathway as compared to Cis-GNs. Conclusion: Therefore, Cis-GNs-FA warrants further in-depth in vitro and in vivo investigations to scale up the technology for clinical translation.
AB - Purpose: Cisplatin is highly effective in the treatment of cervical cancer. However, in therapeutic doses, cisplatin induces several adverse effects due to undesirable tissue distribution. Therefore, it is worth targeting cisplatin in cervical cancer cells by implicating non-aggregated ligand-modified nanotherapeutics. Methods and results: Here, we report the preparation of non-aggregated folic acid-conjugated gelatin nanoparticles of cisplatin (Cis-GNs-FA) by two-step desolvation method with mean particle size of 210.6±9.6nm and 140.5±10.9nm for Cis-GNs to improve the drug delivery in cervical cancer, HeLa cells. FTIR and DSC spectra confirmed the presence and stability of cisplatin in gelatin matrix. Furthermore, amorphization of cisplatin in nanoparticles was ascertained by PXRD. Drug release followed a first-order release kinetic at both pH~5.6 (cervical cancer pH) and pH~7.4. In addition, a significant (P<0.05) decrease in IC50 value (8.3μM) and enhanced apoptosis were observed in HeLa cells treated with Cis-GNs-FA as compared to Cis-GNs (15.1μM) and cisplatin solution (40.2μM). In contrast, A549 lung cancer cells did not discriminate between Cis-GNs-FA and Cis-GNs due to the absence of folate receptors-α (FR-α). Consistently, higher cellular uptake, 80.54±7.60% was promoted by Cis-GNs-FA significantly (two-way ANOVA, P<0.05) greater than 51.68±9.78%, by Cis-GNs. This was also illustrated by CLSM images, which indicated that Cis-GNs-FA preferably accumulated in the cytoplasm of HeLa cells nearby nucleus by following receptor-mediated endocytosis pathway as compared to Cis-GNs. Conclusion: Therefore, Cis-GNs-FA warrants further in-depth in vitro and in vivo investigations to scale up the technology for clinical translation.
KW - Apoptosis
KW - Cellular uptake
KW - Cervical cancer
KW - Cisplatin
KW - Cytotoxicity
KW - Folate
KW - Gelatin nanoparticles
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U2 - 10.1016/j.biopha.2014.10.016
DO - 10.1016/j.biopha.2014.10.016
M3 - Article
C2 - 25661330
AN - SCOPUS:84922264010
SN - 0753-3322
VL - 69
SP - 1
EP - 10
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
ER -