Removal of Tumor Cells from Spermatogonial Cells by Application of Smart Nanoparticles


avatar Ronak Shabani ORCID 1 , 2 , *

Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran

how to cite: Shabani R. Removal of Tumor Cells from Spermatogonial Cells by Application of Smart Nanoparticles. Gene Cell Tissue. 2019;6(2):e91999. doi: 10.5812/gct.91999.

Dear Editor,

In recent years, despite successful treatment in more than 70% of testicular cancers in children (1) with radiotherapy and chemotherapy, 20% - 30% of them have azoospermia in the puberty or a significant reduction in sperm count (1, 2). This could endanger their quality of life (3). Currently, there are no methods for preserving the fertility of children with testicular cancer before puberty (4, 5) and the use of spermatogonial stem cells (SSCs) can be effective as an approach to sustain the fertility of these children (6).

Fluorescent-activated cell sorting (FACS) or magnetic-activated cell sorting (MACS) have been used to separate cancer cells from normal cells in previous studies (7-10). Cisplatin is a platinum-based chemotherapy drug that it is widely used for the treatment of a variety of cancers such as ovarian cancer and germ cell tumors (11). Despite cisplatin that specifically exerts its function against testicular tumors, unconventional chemotherapy is not effective, and at the same time transfers chemotherapy agents to both normal and tumoral cells (11).

Use of functionalized nanoparticles (NPs) due to their ability to deliver targeted drugs is considered an up-and-coming strategy (12). The NPs are used as delivery medications into doses of chemotherapy drugs or therapeutic genes in the malignant cells; however, it does not affect healthy cells. Internalization of the NPs into cancer cells is longer due to the positive charge. In addition, it increases drug circulation time and leads to hydrophilic levels, which increases drug delivery to cancer cells (13). Poly-lactic-co-glycolic acid (PLGA) is one of the most successful polymers used in drug delivery, and its hydrolysis results in the production of lactic acid and glycolic acid metabolite monomers (13). Therefore, we have used cisplatin-loaded PLGA nanoparticles in comparison to free cisplatin treatment as a new method for the decontamination of tumoral cells from SSCs (13). We used folic acid in this study, which was added to the surface of the NPs that has a large receptor on the tumor cell for targeting. The MTT assay was performed to evaluate the toxicity of NPs and our results showed that no toxicity of blank NPs on SSCs was observed (13).

In a study, it was observed that the survival rate of tumoral cells was significantly reduced in the group that received the free cisplatin in both SSC and tumoral cells, and there were significant differences between IC50 results with respect to effective doses of cisplatin. The number of TUNEL-positive cells was increased, and the expression of Bax and caspase-3 was up-regulated in tumoral cells for that group, which received an effective dose of cisplatin (14).

Another study showed that drug delivery by NPs is more effective than free cisplatin. In this study, drug release was controlled and our results emphasize that drug delivery can be applied as a novel method for the separation of normal cells from tumoral cells. Use of smart NPs will increase the therapeutic effect and will be useful for the elimination of tumoral cells. Moreover, no tumor recurrence was observed after cell suspension transplantation following the treatment by NPs (13). Eslahi et al. described another technique for decontamination of tumoral cells from SSCs by Folate-Silica-Gold Nanorods), their results demonstrated that the cytotoxicity of F-SiGNRs was increased in tumoral cells in comparison to SSCs (15).

In conclusion, we described a new method for the elimination of cancerous cells from SSCs. To the best of our knowledge, this is the first study focused on research toward delivering. The cisplatin-loaded PLGA nanoparticles provide a new approach for the elimination of cancer cell from spermatogonial stem cells (13).



  • 1.

    Jemal A, Clegg LX, Ward E, Ries LA, Wu X, Jamison PM, et al. Annual report to the nation on the status of cancer, 1975-2001, with a special feature regarding survival. Cancer. 2004;101(1):3-27. doi: 10.1002/cncr.20288. [PubMed: 15221985].

  • 2.

    Humpl T, Schramm P, Gutjahr P. Male fertility in long-term survivors of childhood ALL. Arch Androl. 1999;43(2):123-9. [PubMed: 10543574].

  • 3.

    Bauld C, Anderson V, Arnold J. Psychosocial aspects of adolescent cancer survival. J Paediatr Child Health. 1998;34(2):120-6. [PubMed: 9588632].

  • 4.

    Oktay K, Oktem O. Fertility preservation medicine: A new field in the care of young cancer survivors. Pediatr Blood Cancer. 2009;53(2):267-73. doi: 10.1002/pbc.22003. [PubMed: 19301406].

  • 5.

    van den Berg H, Repping S, van der Veen F. Parental desire and acceptability of spermatogonial stem cell cryopreservation in boys with cancer. Hum Reprod. 2007;22(2):594-7. doi: 10.1093/humrep/del375. [PubMed: 17000650].

  • 6.

    Brinster RL. Male germline stem cells: From mice to men. Science. 2007;316(5823):404-5. doi: 10.1126/science.1137741. [PubMed: 17446391]. [PubMed Central: PMC4889115].

  • 7.

    Geens M, Van de Velde H, De Block G, Goossens E, Van Steirteghem A, Tournaye H. The efficiency of magnetic-activated cell sorting and fluorescence-activated cell sorting in the decontamination of testicular cell suspensions in cancer patients. Hum Reprod. 2007;22(3):733-42. doi: 10.1093/humrep/del418. [PubMed: 17082221].

  • 8.

    Dovey SL, Valli H, Hermann BP, Sukhwani M, Donohue J, Castro CA, et al. Eliminating malignant contamination from therapeutic human spermatogonial stem cells. J Clin Invest. 2013;123(4):1833-43. doi: 10.1172/JCI65822. [PubMed: 23549087]. [PubMed Central: PMC3613920].

  • 9.

    Hermann BP, Sukhwani M, Salati J, Sheng Y, Chu T, Orwig KE. Separating spermatogonia from cancer cells in contaminated prepubertal primate testis cell suspensions. Hum Reprod. 2011;26(12):3222-31. doi: 10.1093/humrep/der343. [PubMed: 22016413]. [PubMed Central: PMC3212882].

  • 10.

    Valli H, Sukhwani M, Dovey SL, Peters KA, Donohue J, Castro CA, et al. Fluorescence- and magnetic-activated cell sorting strategies to isolate and enrich human spermatogonial stem cells. Fertil Steril. 2014;102(2):566-80. doi: 10.1016/j.fertnstert.2014.04.036. [PubMed: 24890267]. [PubMed Central: PMC4128386].

  • 11.

    Kartalou M, Essigmann JM. Recognition of cisplatin adducts by cellular proteins. Mutat Res. 2001;478(1-2):1-21. [PubMed: 11406166].

  • 12.

    Moradi F, Parsaie H, Charkhat Gorgich EA. Targeted delivery of therapeutic agents by smart nanocarrier for treatment of parkinson’s disease: A novel brain targeting approach. Gene Cell Tissue. 2019;6(2). e91213. doi: 10.5812/gct.91213.

  • 13.

    Shabani R, Ashjari M, Ashtari K, Izadyar F, Behnam B, Khoei S, et al. Elimination of mouse tumor cells from neonate spermatogonial cells utilizing cisplatin-entrapped folic acid-conjugated poly(lactic-co-glycolic acid) nanoparticles in vitro. Int J Nanomedicine. 2018;13:2943-54. doi: 10.2147/IJN.S155052. [PubMed: 29849458]. [PubMed Central: PMC5965374].

  • 14.

    Shabani R, Ashtari K, Behnam B, Izadyar F, Asgari H, Asghari Jafarabadi M, et al. In vitro toxicity assay of cisplatin on mouse acute lymphoblastic leukaemia and spermatogonial stem cells. Andrologia. 2016;48(5):584-94. doi: 10.1111/and.12490. [PubMed: 26428408].

  • 15.

    Eslahi N, Shakeri-Zadeh A, Ashtari K, Pirhajati-Mahabadi V, Tohidi Moghadam T, Shabani R, et al. In vitro cytotoxicity of folate-silica-gold nanorods on mouse acute lymphoblastic leukemia and spermatogonial cells. Cell J. 2019;21(1):14-26. doi: 10.22074/cellj.2019.5691. [PubMed: 30507084]. [PubMed Central: PMC6275430].

Copyright © 2019, Gene, Cell and Tissue. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.