Noscapinoids bearing silver nanocrystals augmented drug delivery, cytotoxicity, apoptosis and cellular uptake in B16F1, mouse melanoma skin cancer cells

作者：Soni Naina; Jyoti Kiran; Jain Upendra Kumar; Katyal Anju; Chandra Ramesh; Madan Jitender^*

来源：Biomedicine & Pharmacotherapy, 2017, 90: 906-913.

DOI：10.1016/j.biopha.2017.04.042

• Melanoma
• Noscapinoids
• Silver nanocrystals
• Cytotoxicity
• Apoptosis
• Cellular uptake

Purpose: Noscapine (Nos) and reduced brominated analogue of noscapine (Red-Br-Nos) prevent cellular proliferation and induce apoptosis in cancer cells either alone or in combination with other chemotherapeutic drugs. However, owing to poor physicochemical properties, Nos and Red-Br-Nos have demonstrated their anticancer activity at higher and multiple doses. Therefore, in present investigation, silver nanocrystals of noscapinoids (Nos-Ag2+ nanocrystals and Red-Br-Nos-Ag2+ nanocrystals) were customized to augment drug delivery, cytotoxicity, apoptosis and cellular uptake in B16F1 mouse melanoma cancer cells.
Methods and results: Nos-Ag2+ nanocrystals and Red-Br-Nos-Ag2+ nanocrystals were prepared separately by precipitation method. The mean particle size of Nos-Ag2+ nanocrystals was measured to be 25.33 +/- 3.52 nm, insignificantly (P > 0.05) different from 27.43 +/- 4.51 nm of Red-Br-Nos-Ag2+ nanocrystals. Furthermore, zeta-potential of Nos-Ag2+ nanocrystals was determined to be -25.3 +/- 3.11 mV significantly (P < 0.05) different from - 15.2 +/- 3.33 mV of Red-Br-Nos-Ag2+ nanocrystals. The shape of tailored nanocrystals was slightly spherical and or irregular in shape. The architecture of Nos-Ag2+ nanocrystals and Red-Br-Nos-Ag2+ nanocrystals was crystalline in nature. FT-IR spectroscopy evinced the successful interaction of Ag2+ nanocrystals with Nos and Red-Br-Nos, respectively. The superior therapeutic efficacy of tailored nanocrystals was measured in terms of enhanced cytotoxicity, apoptosis and cellular uptake. The Nos-Ag2+ nanocrystals and Red-Br-Nos-Ag2+ nanocrystals exhibited an IC50 of 16.6 mM and 6.5 mu M, significantly (P < 0.05) lower than 38.5 mu M of Nos and 10.3 mu M of Red-Br-Nos, respectively. Finally, cellular morphological alterations in B16F1 cells upon internalization of Nos-Ag2+ nanocrystals and Red-Br-Nos-Ag2+ nanocrystals provided the evidences for accumulation within membrane-bound cytoplasmic vacuoles and in enlarged lysosomes and thus triggered mitochondria mediated apoptosis via caspase activation.
Conclusion: Preliminary investigations substantiated that Nos-Ag2+ nanocrystals and Red-Br-Nos-Ag2+ nanocrystals must be further explored and utilized for the delivery of noscapinoids to melanoma cancer cells.

• 出版日期2017-6