Skip to main content
SpringerLink
Log in

Doxorubicin-loaded star-shaped copolymer PLGA-vitamin E TPGS nanoparticles for lung cancer therapy

  • Delivery Systems
  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

A doxorubicin-loaded mannitol-functionalized poly(lactide-co-glycolide)-b-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles (DOX-loaded M-PLGA-b-TPGS NPs) were prepared by a modified nanoprecipitation method. The NPs were characterized by the particle size, surface morphology, particle stability, in vitro drug release and cellular uptake efficiency. The NPs were near-spherical with narrow size distribution. The size of M-PLGA-b-TPGS NPs was ~110.9 nm (much smaller than ~143.7 nm of PLGA NPs) and the zeta potential was −35.8 mV (higher than −42.6 mV of PLGA NPs). The NPs exhibited a good redispersion since the particle size and surface charge hardly changed during 3-month storage period. In the release medium (phosphate buffer solution vs. fetal bovine serum), the cumulative drug release of DOX-loaded M-PLGA-b-TPGS, PLGA-b-TPGS, and PLGA NPs were 76.41 versus 83.11 %, 58.94 versus 73.44 % and 45.14 versus 53.12 %, respectively. Compared with PLGA-b-TPGS NPs and PLGA NPs, the M-PLGA-b-TPGS NPs possessed the highest cellular uptake efficiency in A549 and H1975 cells (lung cancer cells). Ultimately, both in vitro and in vivo antitumor activities were evaluated. The results showed that M-PLGA-b-TPGS NPs could achieve a significantly higher level of cytotoxicity in cancer cells and a better antitumor efficiency on xenograft BALB/c nude mice tumor model than free DOX. In conclusion, the DOX-loaded M-PLGA-b-TPGS could be used as a potential DOX-loaded nanoformulation in lung cancer chemotherapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.

    Article  Google Scholar 

  2. Bunn PA Jr. Worldwide overview of the current status of lung cancer diagnosis and treatment. Arch Pathol Lab Med. 2012;136:1478–81.

    Article  Google Scholar 

  3. Mei L, Zhang Z, Zhao L, Huang L, Yang XL, Tang J, et al. Pharmaceutical nanotechnology for oral delivery of anticancer drugs. Adv Drug Deliv Rev. 2013;65:880–90.

    Article  Google Scholar 

  4. Zhang C, Wang W, Liu T, Wu Y, Guo H, Wang P, et al. Doxorubicin-loaded glycyrrhetinic acid-modified alginate nanoparticles for liver tumor chemotherapy. Biomaterials. 2012;33:2187–96.

    Article  Google Scholar 

  5. Zeng X, Tao W, Wang Z, Zhang X, Zhu H, Wu Y, et al. Docetaxel-loaded nanoparticles of dendritic amphiphilic block copolymer H40-PLA-b-TPGS for cancer treatment. Part Part Syst Charact. 2015;32:112–22.

    Article  Google Scholar 

  6. Chauhan VP, Jain RK. Strategies for advancing cancer nanomedicine. Nat Mater. 2013;12:958–62.

    Article  Google Scholar 

  7. Juliano R. Nanomedicine: is the wave cresting? Nat Rev Drug Discov. 2013;12:171–2.

    Article  Google Scholar 

  8. Liang R, Wang J, Wu X, Dong L, Deng R, Wang K, et al. Multifunctional biodegradable polymer nanoparticles with uniform sizes: generation and in vitro anti-melanoma activity. Nanotechnology. 2013;24:455302.

    Article  Google Scholar 

  9. Zhang X, Dong Y, Zeng X, Liang X, Li X, Tao W, et al. The effect of autophagy inhibitors on drug delivery using biodegradable polymer nanoparticles in cancer treatment. Biomaterials. 2014;35:1932–43.

    Article  Google Scholar 

  10. Han S, Liu Y, Nie X, Xu Q, Jiao F, Li W, et al. Efficient delivery of antitumor drug to the nuclei of tumor cells by amphiphilic biodegradable poly(l-aspartic acid-co-lactic acid)/DPPE co-polymer nanoparticles. Small. 2012;8:1596–606.

    Article  Google Scholar 

  11. Meng J, Liang X, Chen X, Zhao Y. Biological characterizations of [Gd@C82(OH)22]n nanoparticles as fullerene derivatives for cancer therapy. Integr Biol. 2013;5:43–7.

    Article  Google Scholar 

  12. Zeng X, Tao W, Mei L, Huang L, Tan C, Feng SS. Cholic acid-functionalized nanoparticles of star-shaped PLGA-vitamin E TPGS copolymer for docetaxel delivery to cervical cancer. Biomaterials. 2013;34:6058–67.

    Article  Google Scholar 

  13. Huang L, Chen H, Zheng Y, Song X, Liu R, Liu K, et al. Nanoformulation of d-alpha-tocopheryl polyethylene glycol 1000 succinate-b-poly(epsilon-caprolactone-ran-glycolide) diblock copolymer for breast cancer therapy. Integr Biol. 2011;3:993–1002.

    Article  Google Scholar 

  14. Hussein-Al-Ali SH, Arulselvan P, Fakurazi S, Hussein MZ, Dorniani D. Arginine–chitosan-and arginine–polyethylene glycol-conjugated superparamagnetic nanoparticles: preparation, cytotoxicity and controlled-release. J Biomater Appl. 2014;29:186–98.

    Article  Google Scholar 

  15. Zhu H, Chen H, Zeng X, Wang Z, Zhang X, Wu Y, et al. Co-delivery of chemotherapeutic drugs with vitamin E TPGS by porous PLGA nanoparticles for enhanced chemotherapy against multi-drug resistance. Biomaterials. 2014;35:2391–400.

    Article  Google Scholar 

  16. Jiang T, Singh B, Li HS, Kim YK, Kang SK, Nah JW, et al. Targeted oral delivery of BmpB vaccine using porous PLGA microparticles coated with M cell homing peptide-coupled chitosan. Biomaterials. 2014;35:2365–73.

    Article  Google Scholar 

  17. Tao W, Zeng X, Zhang J, Zhu H, Chang D, Zhang X, et al. Synthesis of cholic acid-core poly([varepsilon]-caprolactone-ran-lactide)-b-poly(ethylene glycol) 1000 random copolymer as a chemotherapeutic nanocarrier for liver cancer treatment. Biomater Sci. 2014;2:1262–74.

    Article  Google Scholar 

  18. Segat D, Tavano R, Donini M, Selvestrel F, Rio-Echevarria I, Rojnik M, et al. Proinflammatory effects of bare and PEGylated ORMOSIL-, PLGA- and SUV-NPs on monocytes and PMNs and their modulation by f-MLP. Nanomedicine (Lond). 2011;6:1027–46.

    Article  Google Scholar 

  19. Toraya-Brown S, Sheen MR, Baird JR, Barry S, Demidenko E, Turk MJ, et al. Phagocytes mediate targeting of iron oxide nanoparticles to tumors for cancer therapy. Integr Biol. 2013;5:159–71.

    Article  Google Scholar 

  20. Tao W, Zeng X, Liu T, Wang Z, Xiong Q, Ouyang C, et al. Docetaxel-loaded nanoparticles based on star-shaped mannitol-core PLGA-TPGS diblock copolymer for breast cancer therapy. Acta Biomater. 2013;9:8910–20.

    Article  Google Scholar 

  21. Luderer F, Löbler M, Rohm HW, Gocke C, Kunna K, Köck K, et al. Biodegradable sirolimus-loaded poly(lactide) nanoparticles as drug delivery system for the prevention of in-stent restenosis in coronary stent application. J Biomater Appl. 2011;25:851–75.

    Article  Google Scholar 

  22. Zhang Z, Tan S, Feng SS. Vitamin E TPGS as a molecular biomaterial for drug delivery. Biomaterials. 2012;33:4889–906.

    Article  Google Scholar 

  23. Muthu MS, Kulkarni SA, Xiong J, Feng SS. Vitamin E TPGS coated liposomes enhanced cellular uptake and cytotoxicity of docetaxel in brain cancer cells. Int J Pharm. 2011;421:332–40.

    Article  Google Scholar 

  24. Mi Y, Liu Y, Feng SS. Formulation of Docetaxel by folic acid-conjugated d-alpha-tocopheryl polyethylene glycol succinate 2000 (Vitamin E TPGS(2 k)) micelles for targeted and synergistic chemotherapy. Biomaterials. 2011;32:4058–66.

    Article  Google Scholar 

  25. Li PY, Lai PS, Hung WC, Syu WJ. Poly(l-lactide)-vitamin E TPGS nanoparticles enhanced the cytotoxicity of doxorubicin in drug-resistant MCF-7 breast cancer cells. Biomacromolecules. 2010;11:2576–82.

    Article  Google Scholar 

  26. Mi Y, Zhao J, Feng SS. Vitamin E TPGS prodrug micelles for hydrophilic drug delivery with neuroprotective effects. Int J Pharm. 2012;438:98–106.

    Article  Google Scholar 

  27. Tan GR, Feng SS, Leong DT. The reduction of anti-cancer drug antagonism by the spatial protection of drugs with PLA-TPGS nanoparticles. Biomaterials. 2014;35:3044–51.

    Article  Google Scholar 

  28. Zhao J, Mi Y, Feng SS. Targeted co-delivery of docetaxel and siPlk1 by herceptin-conjugated vitamin E TPGS based immunomicelles. Biomaterials. 2013;34:3411–21.

    Article  Google Scholar 

  29. Pridgen EM, Alexis F, Kuo TT, Levy-Nissenbaum E, Karnik R, Blumberg RS, et al. Transepithelial transport of Fc-targeted nanoparticles by the neonatal fc receptor for oral delivery. Sci Transl Med. 2013;5:213ra167.

    Article  Google Scholar 

  30. Feng SS, Mei L, Anitha P, Gan CW, Zhou W. Poly(lactide)-vitamin E derivative/montmorillonite nanoparticle formulations for the oral delivery of Docetaxel. Biomaterials. 2009;30:3297–306.

    Article  Google Scholar 

  31. Li D, Ping Y, Xu F, Yu H, Pan H, Huang H, et al. Construction of a star-shaped copolymer as a vector for FGF receptor-mediated gene delivery in vitro and in vivo. Biomacromolecules. 2010;11:2221–9.

    Article  Google Scholar 

  32. Ma D, Lin QM, Zhang LM, Liang YY, Xue W. A star-shaped porphyrin-arginine functionalized poly(l-lysine) copolymer for photo-enhanced drug and gene co-delivery. Biomaterials. 2014;35:4357–67.

    Article  Google Scholar 

  33. Kozak D, Anderson W, Vogel R, Chen S, Antaw F, Trau M. Simultaneous size and zeta-potential measurements of individual nanoparticles in dispersion using size-tunable pore sensors. ACS Nano. 2012;6:6990–7.

    Article  Google Scholar 

  34. Shi J, Xiao Z, Kamaly N, Farokhzad OC. Self-assembled targeted nanoparticles: evolution of technologies and bench to bedside translation. Acc Chem Res. 2011;44:1123–34.

    Article  Google Scholar 

  35. Shi J, Votruba AR, Farokhzad OC, Langer R. Nanotechnology in drug delivery and tissue engineering: from discovery to applications. Nano Lett. 2010;10:3223–30.

    Article  Google Scholar 

  36. Prabaharan M, Grailer JJ, Pilla S, Steeber DA, Gong S. Folate-conjugated amphiphilic hyperbranched block copolymers based on Boltorn H40, poly(l-lactide) and poly(ethylene glycol) for tumor-targeted drug delivery. Biomaterials. 2009;30:3009–19.

    Article  Google Scholar 

  37. Zhao J, Feng SS. Effects of PEG tethering chain length of vitamin E TPGS with a Herceptin-functionalized nanoparticle formulation for targeted delivery of anticancer drugs. Biomaterials. 2014;35:3340–7.

    Article  Google Scholar 

  38. Liu Y, Feng SS. The synergistic effect of herceptin and docetaxel in polylactide-d-alpha-tocopheryl polyethylene glycol succinate (PLA-TPGS) nanoparticles. J Control Release. 2011;152(Suppl 1):e64–5.

    Article  Google Scholar 

  39. Rothenfluh DA, Hubbell JA. Integration column: biofunctional polymeric nanoparticles for spatio-temporal control of drug delivery and biomedical applications. Integr Biol. 2009;1:446–51.

    Article  Google Scholar 

  40. Kamaly N, Xiao Z, Valencia PM, Radovic-Moreno AF, Farokhzad OC. Targeted polymeric therapeutic nanoparticles: design, development and clinical translation. Chem Soc Rev. 2012;41:2971–3010.

    Article  Google Scholar 

  41. Schutz CA, Juillerat-Jeanneret L, Mueller H, Lynch I, Riediker M. Therapeutic nanoparticles in clinics and under clinical evaluation. Nanomedicine (Lond). 2013;8:449–67.

    Article  Google Scholar 

  42. Ungaro F, d’Angelo I, Coletta C, di Villa d’Emmanuele, Bianca R, Sorrentino R, Perfetto B, et al. Dry powders based on PLGA nanoparticles for pulmonary delivery of antibiotics: modulation of encapsulation efficiency, release rate and lung deposition pattern by hydrophilic polymers. J Control Release. 2012;157:149–59.

    Article  Google Scholar 

  43. Bin Y, Sheng-Yong G, Jin-Ye W. Physical stability of cholesterol derivatives combined with liposomes and their in vitro behavior. Eng Med Biol Soc (EMBC), 2013 35th Annual International Conference of the IEEE 2013. pp. 4114–4117.

  44. Peng Z, Wang CX, Fang EH, Lu XM, Wang GB, Tong Q. Co-delivery of doxorubicin and SATB1 shRNA by thermosensitive magnetic cationic liposomes for gastric cancer therapy. PloS One. 2014;9:e92924.

    Article  Google Scholar 

  45. Shin SJ, Beech JR, Kelly KA. Targeted nanoparticles in imaging: paving the way for personalized medicine in the battle against cancer. Integr Biol. 2013;5:29–42.

    Article  Google Scholar 

  46. Parchur AK, Ansari AA, Singh BP, Hasan TN, Syed NA, Rai SB, et al. Enhanced luminescence of CaMoO4: Eu by core@shell formation and its hyperthermia study after hybrid formation with Fe3O4: cytotoxicity assessment on human liver cancer cells and mesenchymal stem cells. Integr Biol. 2014;6:53–64.

    Article  Google Scholar 

  47. Costa RR, Girotti A, Santos M, Arias FJ, Mano JF, Rodriguez-Cabello JC. Cellular uptake of multilayered capsules produced with natural and genetically engineered biomimetic macromolecules. Acta Biomater. 2014;10:2653–62.

    Article  Google Scholar 

  48. Shima F, Uto T, Akagi T, Baba M, Akashi M. Size effect of amphiphilic poly(gamma-glutamic acid) nanoparticles on cellular uptake and maturation of dendritic cells in vivo. Acta Biomater. 2013;9:8894–901.

    Article  Google Scholar 

  49. Collnot EM, Baldes C, Wempe MF, Kappl R, Huttermann J, Hyatt JA, et al. Mechanism of inhibition of P-glycoprotein mediated efflux by vitamin E TPGS: influence on ATPase activity and membrane fluidity. Mol Pharm. 2007;4:465–74.

    Article  Google Scholar 

Download references

Acknowledgments

The authors are grateful for financial support from the National Natural Science Foundation of China (No. 31270019, 51203085), Science, Technology & Innovation Commission of Shenzhen Municipality (No. JCYJ20140718171607436), and Program for New Century Excellent Talents in University (NCET-11-0275).

Disclosure

The authors report no conflicts of interest in this work.

Author information

Author notes

    Authors and Affiliations

    1. School of Life Sciences, Tsinghua University, Beijing, 100084, People’s Republic of China

      Jinxie Zhang, Wei Tao, Xudong Zhang, Lin Mei, Xiaowei Zeng & Laiqiang Huang

    2. The Shenzhen Key Lab of Gene and Antibody Therapy, Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, People’s Republic of China

      Jinxie Zhang, Wei Tao, Danfeng Chang, Teng Wang, Xudong Zhang, Lin Mei, Xiaowei Zeng & Laiqiang Huang

    3. Second Clinical Medical College, Jinan University, Shenzhen, 518020, People’s Republic of China

      Yuhan Chen

    4. Department of Chemistry, Tsinghua University, Beijing, 100084, People’s Republic of China

      Danfeng Chang & Teng Wang

    Authors
    1. Jinxie Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Wei Tao
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Yuhan Chen
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Danfeng Chang
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Teng Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Xudong Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Lin Mei
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Xiaowei Zeng
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Laiqiang Huang
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Xiaowei Zeng or Laiqiang Huang.

    Additional information

    Jinxie Zhang, Wei Tao, Yuhan Chen have contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Zhang, J., Tao, W., Chen, Y. et al. Doxorubicin-loaded star-shaped copolymer PLGA-vitamin E TPGS nanoparticles for lung cancer therapy. J Mater Sci: Mater Med 26, 165 (2015). https://doi.org/10.1007/s10856-015-5498-z

    Download citation

    • Received:

    • Accepted:

    • Published:

    • DOI: https://doi.org/10.1007/s10856-015-5498-z

    Keywords

    Search

    Navigation