Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Cervical Cancer Gene Therapy by Gene Loaded PEG-PLA Nanomedicine

  • Liu, Bo (Department of Internal Medicine Oncology, Shandong Tumor Hospital and Institute) ;
  • Han, Shu-Mei (Department of Internal Medicine Oncology, Shandong Tumor Hospital and Institute) ;
  • Tang, Xiao-Yong (Department of Internal Medicine Oncology, Shandong Tumor Hospital and Institute) ;
  • Han, Li (Department of Internal Medicine Oncology, Shandong Tumor Hospital and Institute) ;
  • Li, Chang-Zhong (Department of Gynecology, Shandong Provincial Hospital Affiliated to Shandong University)
  • Published : 2014.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Background and Aims: Advances in the treatment of cervical cancer over the last decade have predominantly involved the development of genes directed at molecular targets. Gene therapy is recognized to be a novel method for the treatment of cervical cancer. Genes can be administered into target cells via nanocarriers. This study aimed to develop systemically administrable nano-vectors. Floate (Fa) containing gene loaded nanoparticles (NPs) could target HeLa human cervical cancer cells through combination with receptors on the cells to increase the nuclear uptake of genetic materials. Methods: Fa was linked onto Poly (ethylene glycol)-b-poly (D, L-lactide) (PEG-PLA) to form Fa-PEG-PLA, and the resulting material was used to load plasmids of enhanced green fluorescence protein (pEGFP) to obtain gene loaded nanoparticles (Fa-NPs/DNA). Physical-chemical characteristics, in vitro release and cytotoxicity of Fa-NPs/DNA were evaluated. The in vitro transfection efficiency of Fa-NPs/DNA was evaluated in HeLa cells and human umbilical vein endothelial cells (HUVEC). PEG-PLA without Fa was used to load pEGFP from NPs/DNA as a control. Results: Fa-NPs/DNA has a particle size of 183 nm and a gene loading quantity of 92%. After 72h of transfection, Fa-NPs/DNA displayed over 20% higher transfection efficiency than NPs/DNA and 40% higher than naked DNA in HeLa cells. However, in HUVECs, no significant difference appeared between Fa-NPs/DNA and NPs/DNA. Conclusions: Fa-PEG-PLA NPs could function as excellent materials for gene loading. This nano-approach could be used as tumor cell targeted medicine for the treatment of cervical cancer.

Keywords

References

  1. AAntic LG, Djikanovic BS, Antic DZ, et al (2014). Differencies in the level of knowledge on cervical cancer among health care students, midwives and patients in Serbia. Asian Pac J Cancer Prev, 15, 3011-5. https://doi.org/10.7314/APJCP.2014.15.7.3011
  2. Buyens K, De Smedt SC, Braeckmans K, et al (2012). Liposome based systems for systemic siRNA delivery: stability in blood sets the requirements for optimal carrier design. J Control Release, 158, 362-70. https://doi.org/10.1016/j.jconrel.2011.10.009
  3. Chen Y, Zhu X, Zhang X, et al (2010). Nanoparticles modified with tumor-targeting scFv deliver siRNA and miRNA for cancer therapy. Mol Ther, 18, 1650-6. https://doi.org/10.1038/mt.2010.136
  4. Elfinger M, Maucksch C, Rudolph C. (2007). Characterization of lactoferrin as a targeting ligand for nonviral gene delivery to airway epithelial cells. Biomaterials, 28, 3448-55. https://doi.org/10.1016/j.biomaterials.2007.04.011
  5. Elzoghby AO (2013). Gelatin-based nanoparticles as drug and gene delivery systems: Reviewing three decades of research. J Control Release, 172, 1075-91. https://doi.org/10.1016/j.jconrel.2013.09.019
  6. Filipi K, Xhani A (2014). Assessment of cervical cytological data in Albanian females. Asian Pac J Cancer Prev, 15, 2129-32. https://doi.org/10.7314/APJCP.2014.15.5.2129
  7. Gao X, Tao W, Lu W, et al (2006). Lectin-conjugated PEG-PLA nanoparticles: preparation and brain delivery after intranasal administration. Biomaterials, 27, 3482-90. https://doi.org/10.1016/j.biomaterials.2006.01.038
  8. Geiger J, Aneja MK, Hasenpusch G, et al (2010). Targeting of the prostacyclin specific IP1 receptor in lungs with molecular conjugates comprising prostaglandin I2 analogues. Biomaterials, 31, 2903-11. https://doi.org/10.1016/j.biomaterials.2009.12.035
  9. Gersch ED, Gissmann L, Garcea RL (2012). New approaches to prophylactic human papillomavirus vaccines for cervical cancer prevention. Antivir Ther, 17, 425-34.
  10. Kahla S, Kochbati L, Maalej M, et al (2014). Situation of HPV16 E2 gene status during radiotherapy treatment of cervical carcinoma. Asian Pac J Cancer Prev, 15, 2869-73. https://doi.org/10.7314/APJCP.2014.15.6.2869
  11. Karadag G, Gungormus Z, Surucu R, et al (2014). Awareness and practices regarding breast and cervical cancer among Turkish women in Gazientep. Asian Pac J Cancer Prev, 15, 1093-8. https://doi.org/10.7314/APJCP.2014.15.3.1093
  12. Lee H, Kim Y, Schweickert PG, et al (2014). A photodegradable gene delivery system for enhanced nuclear gene transcription. Biomaterials, 35, 1040-9. https://doi.org/10.1016/j.biomaterials.2013.10.030
  13. Lin C, Huang F, Zhang YJ, et al (2014). Roles of MiR-101 and its target gene Cox-2 in early diagnosis of cervical cancer in Uygur women. Asian Pac J Cancer Prev, 15, 45-8. https://doi.org/10.7314/APJCP.2014.15.1.45
  14. Luu HN, Dahlstrom KR, Mullen PD, et al (2013). Comparison of the accuracy of Hybrid Capture II and polymerase chain reaction in detecting clinically important cervical dysplasia: a systematic review and meta-analysis. Cancer Med, 2, 367-90. https://doi.org/10.1002/cam4.83
  15. Ma JQ, Kurban S, Zhao JD, et al (2014). Epigenetic regulation of human riboflavin transporter 2 (hRFT2) in cervical cancers from Uighur women. Asian Pac J Cancer Prev, 15, 2485-9. https://doi.org/10.7314/APJCP.2014.15.6.2485
  16. Meads C, Auguste P, Davenport C, et al (2013). Positron emission tomography/computerised tomography imaging in detecting and managing recurrent cervical cancer: systematic review of evidence, elicitation of subjective probabilities and economic modelling. Health Technol Assess, 17, 1-323.
  17. Narayan G, Murty VV (2010). Integrative genomic approaches in cervical cancer: implications for molecular pathogenesis. Future Oncol, 6, 1643-52. https://doi.org/10.2217/fon.10.114
  18. Parveen S, Misra R, Sahoo SK (2012). Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging. Nanomedicine, 8, 147-66. https://doi.org/10.1016/j.nano.2011.05.016
  19. Podolska K, Stachurska A, Hajdukiewicz K, Malecki M (2012). Gene therapy prospects--intranasal delivery of therapeutic genes. Adv Clin Exp Med, 21, 525-34.
  20. Schadlich A, Caysa H, Mueller T, et al (2011). Tumor accumulation of NIR fluorescent PEG-PLA nanoparticles: impact of particle size and human xenograft tumor model. ACS Nano, 5, 8710-20. https://doi.org/10.1021/nn2026353
  21. Shi Y, Huang W, Liang R, et al (2013). Improvement of in vivo efficacy of recombinant human erythropoietin by encapsulation in PEG-PLA micelle. Int J Nanomedicine, 8, 1-11. https://doi.org/10.2217/nnm.12.179
  22. Takai N, Kira N, Ishii T, et al (2011). Novel chemotherapy using histone deacetylase inhibitors in cervical cancer. Asian Pac J Cancer Prev, 12, 575-80.
  23. Tsai HC, Chang WH, Lo CL, et al (2010). Graft and diblock copolymer multifunctional micelles for cancer chemotherapy and imaging. Biomaterials, 31, 2293-301. https://doi.org/10.1016/j.biomaterials.2009.11.059
  24. Tungsrithong N, Kasinpila C, Maneenin C, et al (2014). Lack of significant effects of Chlamydia trachomatis infection on cervical cancer risk in a nested case-control study in North-East Thailand. Asian Pac J Cancer Prev, 15, 1497-500. https://doi.org/10.7314/APJCP.2014.15.3.1497
  25. Vachani A, Moon E, Wakeam E, et al (2011). Gene therapy for lung neoplasms. Clin Chest Med, 32, 865-85. https://doi.org/10.1016/j.ccm.2011.08.006
  26. Wang S, Luo Y, Zeng S, et al (2013). Dodecanol-poly (D, L-lactic acid)-b-poly (ethylene glycol)-folate (Dol-PLA-PEG-FA) nanoparticles: evaluation of cell cytotoxicity and selecting capability in vitro. Colloids Surf B Biointerfaces, 102, 130-5. https://doi.org/10.1016/j.colsurfb.2012.07.030
  27. Wang YQ, Su J, Wu F, et al (2012). Biscarbamate cross-linked polyethylenimine derivative with low molecular weight, low cytotoxicity, and high efficiency for gene delivery. Int J Nanomedicine, 7, 693-704.
  28. Xia H, Gao X, Gu G, et al (2012). Penetratin-functionalized PEG-PLA nanoparticles for brain drug delivery. Int J Pharm, 436, 840-50. https://doi.org/10.1016/j.ijpharm.2012.07.029
  29. Xiao RZ, Zeng ZW, Zhou GL, et al (2010). Recent advances in PEG-PLA block copolymer nanoparticles. Int J Nanomedicine, 5, 1057-65.
  30. Yang S, Chen Y, Gu K, et al (2013). Novel intravaginal nanomedicine for the targeted delivery of saquinavir to CD4+ immune cells. Int J Nanomedicine, 8, 2847-58.
  31. Yu DH, Lu Q, Xie J, et al (2010). Peptide-conjugated biodegradable nanoparticles as a carrier to target paclitaxel to tumor neovasculature. Biomaterials, 31, 2278-92. https://doi.org/10.1016/j.biomaterials.2009.11.047
  32. Yu W, Liu C, Liu Y, et al (2010). Mannan-modified solid lipid nanoparticles for targeted gene delivery to alveolar macrophages. Pharm Res, 27, 1584-96. https://doi.org/10.1007/s11095-010-0149-z
  33. Zhao LW, Zhong XH, Yang SY et al (2014). Inotodiol inhabits proliferation and induces apoptosis through modulating expression of cycline, p27, bcl-2, and bax in human cervical cancer Hela cells. Asian Pac J Cancer Prev, 15, 3195-9. https://doi.org/10.7314/APJCP.2014.15.7.3195
  34. Zhang L, Hu CH, Cheng SX, Zhuo RX (2010). Hyperbranched amphiphilic polymer with folate mediated targeting property. Colloids Surf B Biointerfaces, 79, 427-33. https://doi.org/10.1016/j.colsurfb.2010.05.014
  35. Zhou X, Gu Y, Zhang SL (2012). Association between p53 codon 72 polymorphism and cervical cancer risk among Asians: a HuGE review and meta-analysis. Asian Pac J Cancer Prev, 13, 4909-14. https://doi.org/10.7314/APJCP.2012.13.10.4909

Cited by

  1. Isomeric Folate-Conjugated Polymeric Micelles Bind to Folate Receptors and Display Anticancer Effects vol.15, pp.17, 2014, https://doi.org/10.7314/APJCP.2014.15.17.7363
  2. Nanotechnology in the management of cervical cancer vol.25, pp.10529276, 2015, https://doi.org/10.1002/rmv.1825
  3. Understanding and exploiting nanoparticles' intimacy with the blood vessel and blood vol.44, pp.22, 2015, https://doi.org/10.1039/C5CS00499C
  4. Recent advances on biocompatible and biodegradable nanoparticles as gene carriers vol.16, pp.6, 2016, https://doi.org/10.1517/14712598.2016.1169269
  5. Molecular Communication and Nanonetwork for Targeted Drug Delivery: A Survey vol.19, pp.4, 2017, https://doi.org/10.1109/COMST.2017.2705740