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Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Bismuth Lipophilic Nanoparticles (BisBAL NP) Inhibit the Growth of Tumor Cells in a Mouse Melanoma Model

Author(s): Claudia María García-Cuellar, Claudio Cabral-Romero*, Rene Hernández-Delgadillo, Juan Manuel Solis-Soto, Irene Meester, Yesennia Sánchez-Pérez, Sergio Eduardo Nakagoshi-Cepeda, Nayely Pineda-Aguilar, Rosa Isela Sánchez-Nájera, María Argelia Akemi Nakagoshi-Cepeda and Shankararaman Chellam

Volume 22, Issue 14, 2022

Published on: 31 March, 2022

Page: [2548 - 2557] Pages: 10

DOI: 10.2174/1871520622666220215124434

Price: $65


Aim: The objective of this study was to analyze the antitumor effect of BisBAL NP in a mouse melanoma model.

Materials and Methods: The antitumor activity of BisBAL NP on murine B16-F10 melanoma cells was determined both in vitro (PrestoBlue cell viability assay and Live/Dead fluorescence) and in vivo, in a mouse model, with the following 15-day treatments: BisBAL NP, negative control (PBS), and cell-death control (docetaxel; DTX). Mouse survival and weight, as well as the tumor volume, were recorded daily during the in vivo study.

Results: BisBAL NP were homogeneous in size (mean diameter, 14.7 nm) and bismuth content. In vitro, 0.1 mg/mL BisBAL NP inhibited B16-F10 cell growth stronger (88%) than 0.1 mg/mL DTX (82%) (*p<0.0001). In vivo, tumors in mice treated with BisBAL NP (50 mg/kg/day) or DTX (10 mg/kg/day) were 76% and 85% smaller than the tumors of negative control mice (*p<0.0001). The average weight of mice was 18.1 g and no statistically significant difference was detected among groups during the study. Alopecia was only observed in all DTX-treated mice. The survival rate was 100% for the control and BisBAL NP groups, but one DTX- treated mouse died at the end of the treatment period. The histopathological analysis revealed that exposure to BisBAL NP was cytotoxic for tumor tissue only, without affecting the liver or kidney.

Conclusion: BisBAL NP decreased the tumor growing in a mouse melanoma model without secondary effects, constituting an innovative low-cost alternative to treat melanoma.

Keywords: Bismuth lipophilic nanoparticles, BisBAL NP, in vivo antitumor activity, mouse melanoma model, live/dead assay, survivin immunochemistry.

Graphical Abstract
Nguyen, K.; Hignett, E.; Khachemoune, A. Current and emerging treatment options for metastatic melanoma: a focused review. Dermatol. Online J, 2020. 26(7), 13030/qt24g3k7z5.
[] [PMID: 32898395]
Sundararajan, S; Thida, AM; Badri, T StatPearls Publishing, 2021, LLC 2021.
Baldermann, C.; Weiskopf, D. Behavioural and structural prevention of skin cancer: Implementation and effectiveness. Journal of Derma-tology, Venereology, and Related Fields, 2020, 71(8), 572-579.
Cassano, R.; Cuconato, M.; Calviello, G.; Serini, S.; Trombino, S. Recent advances in nanotechnology for the treatment of melanoma. Molecules, 2021, 26(4), 785.
[] [PMID: 33546290]
Liu, J.; Sun, L.; Li, L.; Zhang, R.; Xu, Z.P. Synergistic cancer photochemotherapy via layered double hydroxide-based trimodal nanomed-icine at very low therapeutic doses. ACS Appl. Mater. Interfaces, 2021, 13(6), 7115-7126.
[] [PMID: 33543935]
Hu, M.; Zhang, J.; Kong, L.; Yu, Y.; Hu, Q.; Yang, T.; Wang, Y.; Tu, K.; Qiao, Q.; Qin, X.; Zhang, Z. Immunogenic hybrid nanovesicles of liposomes and tumor-derived nanovesicles for cancer immunochemotherapy. ACS Nano, 2021, 15(2), 3123-3138.
[] [PMID: 33470095]
Hernandez-Delgadillo, R.; García-Cuéllar, C.M.; Sánchez-Pérez, Y.; Pineda-Aguilar, N.; Martínez-Martínez, M.A.; Rangel-Padilla, E.E.; Nakagoshi-Cepeda, S.E.; Solís-Soto, J.M.; Sánchez-Nájera, R.I.; Nakagoshi-Cepeda, M.A.A.; Chellam, S.; Cabral-Romero, C. In vitro eval-uation of the antitumor effect of bismuth lipophilic nanoparticles (BisBAL NPs) on breast cancer cells. Int. J. Nanomedicine, 2018, 13, 6089-6097.
[] [PMID: 30323596]
Cabral-Romero, C.; Solís-Soto, J.M.; Sánchez-Pérez, Y.; Pineda-Aguilar, N.; Meester, I.; Pérez-Carrillo, E.; Nakagoshi-Cepeda, S.E.; Sánchez-Nájera, R.I.; Nakagoshi-Cepeda, M.A.A.; Hernandez-Delgadillo, R.; Chellam, S.; García-Cuéllar, C.M. Antitumor activity of a hy-drogel loaded with lipophilic bismuth nanoparticles on cervical, prostate, and colon human cancer cells. Anticancer Drugs, 2020, 31(3), 251-259.
[] [PMID: 31764012]
Martínez-Pérez, F.; García-Cuellar, C.M.; Hernandez-Delgadillo, R.; Zaragoza-Magaña, V.; Sánchez-Pérez, Y.; Meester, I.; Nakagoshi-Cepeda, S.E.; Solís-Soto, J.M.; Nakagoshi-Cepeda, M.A.A.; Chellam, S.; Cabral-Romero, C. Comparative study of antitumor activity be-tween lipophilic bismuth nanoparticles (BisBAL NPs) and chlorhexidine on human squamous cell carcinoma. J. Nanomater., 2019, 2019, 8148219.
Badireddy, A.R.; Hernandez-Delgadillo, R.; Sánchez-Nájera, R.I.; Chellam, S.; Cabral-Romero, C. Synthesis and characterization of lipo-philic bismuth dimercaptopropanol nanoparticles and their effects on oral microorganisms growth and biofilm formation. J. Nanopart. Res., 2014, 16(6), 2456.
Xu, M.; McCanna, D.J.; Sivak, J.G. Use of the viability reagent PrestoBlue in comparison with alamarBlue and MTT to assess the viability of human corneal epithelial cells. J. Pharmacol. Toxicol. Methods, 2015, 71, 1-7.
[] [PMID: 25464019]
Gonzalez, T.L.; Hancock, M.; Sun, S.; Gersch, C.L.; Larios, J.M.; David, W.; Hu, J.; Hayes, D.F.; Wang, S.; Rae, J.M. Targeted degradation of activating estrogen receptor ligand-binding domain mutations in human breast cancer. Breast Cancer Res. Treat., 2020, 180(3), 611-622.
[] [PMID: 32067153]
da Silva, P.B.; Machado, R.T.A.; Pironi, A.M.; Alves, R.C.; de Araújo, P.R.; Dragalzew, A.C.; Dalberto, I.; Chorilli, M. Recent advances in the use of metallic nanoparticles with antitumoral action - Review. Curr. Med. Chem., 2019, 26(12), 2108-2146.
[] [PMID: 29446728]
Vinardell, M.P.; Mitjans, M. Antitumor activities of metal oxide nanoparticles. Nanomaterials (Basel), 2015, 5(2), 1004-1021.
[] [PMID: 28347048]
Alphandéry, E. Bio-synthesized iron oxide nanoparticles for cancer treatment. Int. J. Pharm., 2020, 586, 119472.
[] [PMID: 32590095]
Sindhwani, S.; Syed, A.M.; Ngai, J.; Kingston, B.R.; Maiorino, L.; Rothschild, J.; MacMillan, P.; Zhang, Y.; Rajesh, N.U.; Hoang, T.; Wu, J.L.Y.; Wilhelm, S.; Zilman, A.; Gadde, S.; Sulaiman, A.; Ouyang, B.; Lin, Z.; Wang, L.; Egeblad, M.; Chan, W.C.W. The entry of nanopar-ticles into solid tumours. Nat. Mater., 2020, 19(5), 566-575.
[] [PMID: 31932672]
Rageh, M.M.; El-Gebaly, R.H.; Afifi, M.M. Antitumor activity of silver nanoparticles in Ehrlich carcinoma-bearing mice. Naunyn Schmiedebergs Arch. Pharmacol., 2018, 391(12), 1421-1430.
[] [PMID: 30178417]
Valenzuela-Salas, L.M.; Girón-Vázquez, N.G.; García-Ramos, J.C.; Torres-Bugarín, O.; Gómez, C.; Pestryakov, A.; Villarreal-Gómez, L.J.; Toledano-Magaña, Y.; Bogdanchikova, N. Antiproliferative and antitumour effect of nongenotoxic silver nanoparticles on melanoma models. Oxid. Med. Cell. Longev., 2019, 2019, 4528241-4528241.
[] [PMID: 31428226]
Liao, C.; Li, Y.; Tjong, S.C. Bactericidal and cytotoxic properties of silver nanoparticles. Int. J. Mol. Sci., 2019, 20(2), E449.
[] [PMID: 30669621]
Ferdous, Z.; Nemmar, A. Health impact of silver nanoparticles: A review of the biodistribution and toxicity following various routes of exposure. Int. J. Mol. Sci., 2020, 21(7), E2375.
[] [PMID: 32235542]
de Lima, R.; Seabra, A.B.; Durán, N. Silver nanoparticles: a brief review of cytotoxicity and genotoxicity of chemically and biogenically synthesized nanoparticles. JAT, 2012, 32(11), 867-879.
[] [PMID: 22696476]
Wang, Y.; Yang, F.; Zhang, H.X.; Zi, X.Y.; Pan, X.H.; Chen, F.; Luo, W.D.; Li, J.X.; Zhu, H.Y.; Hu, Y.P. Cuprous oxide nanoparticles inhibit the growth and metastasis of melanoma by targeting mitochondria. Cell Death Dis., 2013, 4(8), e783.
[] [PMID: 23990023]
Balivada, S.; Rachakatla, R.S.; Wang, H.; Samarakoon, T.N.; Dani, R.K.; Pyle, M.; Kroh, F.O.; Walker, B.; Leaym, X.; Koper, O.B.; Tamu-ra, M.; Chikan, V.; Bossmann, S.H.; Troyer, D.L. A/C magnetic hyperthermia of melanoma mediated by iron(0)/iron oxide core/shell magnetic nanoparticles: a mouse study. BMC Cancer, 2010, 10(1), 119.
[] [PMID: 20350328]
Nigam, S.; Bahadur, D. Doxorubicin-loaded dendritic-Fe3O4 supramolecular nanoparticles for magnetic drug targeting and tumor regres-sion in spheroid murine melanoma model. Nanomedicine , 2018, 14(3), 759-768.
[] [PMID: 29339187]
Kalyanaraman, B.; Cheng, G.; Hardy, M.; Ouari, O.; Lopez, M.; Joseph, J.; Zielonka, J.; Dwinell, M.B. A review of the basics of mito-chondrial bioenergetics, metabolism, and related signaling pathways in cancer cells: Therapeutic targeting of tumor mitochondria with lip-ophilic cationic compounds. Redox Biol., 2018, 14, 316-327.
[] [PMID: 29017115]
Baranyi, M.; Rittler, D.; Molnár, E.; Shirasawa, S.; Jalsovszky, I.; Varga, I.K. Heged s, L.; Németh, A.; Dank, M.; Aigner, C.; Tóvári, J.; Tímár, J.; Heged s, B.; Garay, T. Next generation lipophilic bisphosphonate shows antitumor effect in colorectal cancer in vitro and in vi-vo. POR, 2020, 26(3), 1957-1969.
[] [PMID: 31902117]
Serafim, T.L.; Carvalho, F.S.; Marques, M.P.; Calheiros, R.; Silva, T.; Garrido, J.; Milhazes, N.; Borges, F.; Roleira, F.; Silva, E.T.; Holy, J.; Oliveira, P.J. Lipophilic caffeic and ferulic acid derivatives presenting cytotoxicity against human breast cancer cells. Chem. Res. Toxicol., 2011, 24(5), 763-774.
[] [PMID: 21504213]
Hosseini, A.; Sahebkar, A. Reversal of doxorubicin-induced cardiotoxicity by using phytotherapy: A review. J. Pharmacopuncture, 2017, 20(4), 243-256.
[PMID: 30151294]
Jedli ková, H; Vokurka, S; Vojtíšek, R; Male ková, A. Alopecia and hair damage induced by oncological therapy. Clinical Oncology: J. Czech and Slovak Oncological Society, 2019, 32(5), 353-359.
Martín, M.; de la Torre-Montero, J.C.; López-Tarruella, S.; Pinilla, K.; Casado, A.; Fernandez, S.; Jerez, Y.; Puente, J.; Palomero, I. Gon-zález Del Val, R.; Del Monte-Millan, M.; Massarrah, T.; Vila, C.; García-Paredes, B.; García-Sáenz, J.A.; Lluch, A. Persistent major alope-cia following adjuvant docetaxel for breast cancer: incidence, characteristics, and prevention with scalp cooling. Breast Cancer Res. Treat., 2018, 171(3), 627-634.
[] [PMID: 29923063]
Ben Kridis, W.; Khanfir, A. Definitive alopecia post-docetaxel. Breast J., 2020, 26(4), 792-793.
[] [PMID: 31541513]
de Weger, V.A.; Beijnen, J.H.; Schellens, J.H. Cellular and clinical pharmacology of the taxanes docetaxel and paclitaxel-a review. Anticancer Drugs, 2014, 25(5), 488-494.
[] [PMID: 24637579]
Elderman, M.; Hugenholtz, F.; Belzer, C.; Boekschoten, M.; van Beek, A.; de Haan, B.; Savelkoul, H.; de Vos, P.; Faas, M. Sex and strain dependent differences in mucosal immunology and microbiota composition in mice. Biol. Sex Differ., 2018, 9(1), 26.
[] [PMID: 29914546]
McMurphy, T.; Xiao, R.; Magee, D.; Slater, A.; Zabeau, L.; Tavernier, J.; Cao, L. The anti-tumor activity of a neutralizing nanobody target-ing leptin receptor in a mouse model of melanoma. PLoS One, 2014, 9(2), e89895-e89895.
[] [PMID: 24587106]
Francis, P.A.; Kris, M.G.; Rigas, J.R.; Grant, S.C.; Miller, V.A. Paclitaxel (Taxol) and docetaxel (Taxotere): active chemotherapeutic agents in lung cancer. Lung Cancer, 1995, 12(Suppl. 1), S163-S172.
[] [PMID: 7551925]
Wagner, A.D.; Syn, N.L.; Moehler, M.; Grothe, W.; Yong, W.P.; Tai, B.C.; Ho, J.; Unverzagt, S. Chemotherapy for advanced gastric cancer. Cochrane Database Syst. Rev., 2017, 8(8), CD004064.
[PMID: 28850174]
Sibaud, V.; Lebœuf, N.R.; Roche, H.; Belum, V.R.; Gladieff, L.; Deslandres, M.; Montastruc, M.; Eche, A.; Vigarios, E.; Dalenc, F.; Lacouture, M.E. Dermatological adverse events with taxane chemotherapy. EJD, 2016, 26(5), 427-443.
[] [PMID: 27550571]
Kenmotsu, H.; Tanigawara, Y. Pharmacokinetics, dynamics and toxicity of docetaxel: Why the Japanese dose differs from the Western dose. Cancer Sci., 2015, 106(5), 497-504.
[] [PMID: 25728850]

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