Advertisement

Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

pH-responsive nanoparticles based on optimized synthetic amphiphilic poly(β-amino esters) for doxorubicin delivery

  • 13 Accesses

Abstract

Synthesis of amphiphilic poly(β-amino esters) (PBAE) was optimized by stepwise feeding of monomers (PBAE-(P-H)) compared with one-pot synthesis (PBAE-(P&H)) based on poly(ethylene glycol) diacrylate (PEGDA) and 1,6-hexanediol diacrylate (HDDA). Interestingly, optimized synthetic PBAE-(P-H) had smaller critical micelle concentration (CMC) of 6.6 μg/mL on average than one-pot synthetic PBAE-(P&H) (10.4 μg/mL). Nanoparticles were prepared based on PBAE-(P-H) and PBAE-(P&H), respectively. PBAE-(P-H) nanoparticles exhibited more narrow size distribution (average size, 105.3 nm; PDI, 0.103) than PBAE-(P&H) nanoparticles (average size, 117.8 nm; PDI, 0.233) demonstrated by dynamic light scattering and transmission electron microscopy. Afterward, PBAE-(P-H) and PBAE-(P&H) nanoparticles were selected to further investigate the properties including charge conversion and pH responsiveness. Doxorubicin (DOX) was encapsulated into nanoparticles. DOX release in vitro was enhanced as the decrease of pH value. Furthermore, DOX-loaded PBAE-(P-H) and PBAE-(P&H) nanoparticles exhibited enhanced cytotoxicity and cellular uptake against HCT116 cells compared with DOX under tumor microenvironment.

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

Scheme 1
Scheme 2
Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. 1.

    Elahi N, Kamali M, Baghersad MH (2018) Recent biomedical applications of gold nanoparticles: a review. Talanta 184:537–556. https://doi.org/10.1016/j.talanta.2018.02.088

  2. 2.

    Miksa B (2015) RSC advances recent progress in designing shell cross-linked polymer capsules for drug delivery. RSC Adv 5:87781–87805. https://doi.org/10.1039/C5RA12882J

  3. 3.

    Neuroscienze D, Farmacologiche R, Negri M et al (2019) Nanovector-mediated drug delivery in spinal cord. Injury. https://doi.org/10.1021/acschemneuro.8b00700

  4. 4.

    Deirram N, Zhang C, Kermaniyan SS et al (2019) pH-responsive polymer nanoparticles for. Drug Deliv 1800917:1–23. https://doi.org/10.1002/marc.201800917

  5. 5.

    Wang Z, Deng X, Ding J, Zhou W, Zheng X, Tang G (2018) Mechanisms of drug release in pH-sensitive micelles for tumour targeted drug delivery system: a review. Int J Pharm 535:253–260. https://doi.org/10.1016/j.ijpharm.2017.11.003

  6. 6.

    Liu Y, Li Y, Keskin D, Shi L (2019) Poly(β-amino esters): synthesis, formulations, and their biomedical applications. Adv Healthc Mater 8:1–24. https://doi.org/10.1002/adhm.201801359

  7. 7.

    Vuorimaa E, Ketola TM, Green JJ, Hanzlíková M, Lemmetyinen H, Langer R, Anderson DG, Urtti A, Yliperttula M (2011) Poly(β-amino ester)-DNA complexes: time-resolved fluorescence and cellular transfection studies. J Control Release 154:171–176. https://doi.org/10.1016/j.jconrel.2011.06.016

  8. 8.

    Deng X, Zheng N, Song Z, Yin L, Cheng J (2014) Trigger-responsive, fast-degradable poly(β-amino ester)s for enhanced DNA unpackaging and reduced toxicity. Biomaterials 35:5006–5015. https://doi.org/10.1016/j.biomaterials.2014.03.005

  9. 9.

    Patil VS, Dziubla TD, Kalika DS (2015) Static and dynamic properties of biodegradable poly(antioxidant β-amino ester) networks based on incorporation of curcumin multiacrylate. Polymer (Guildf) 75:88–96. https://doi.org/10.1016/j.polymer.2015.08.034

  10. 10.

    Altuncu S, Demir Duman F, Gulyuz U et al (2019) Structure-property relationships of novel phosphonate-functionalized networks and gels of poly(β-amino esters). Eur Polym J 113:155–164. https://doi.org/10.1016/j.eurpolymj.2019.01.052

  11. 11.

    Kim J, Shamul JG, Shah SR, Shin A, Lee BJ, Quinones-Hinojosa A, Green JJ (2018) Verteporfin-loaded poly(ethylene glycol)-poly(beta-amino ester)-poly(ethylene glycol) triblock micelles for cancer therapy. Biomacromolecules 19:3361–3370. https://doi.org/10.1021/acs.biomac.8b00640

  12. 12.

    Wen K, Zhou M, Lu H et al (2018) Near-infrared/pH dual-sensitive Nanocarriers for enhanced intracellular delivery of doxorubicin. ACS Biomater Sci Eng 4:4244–4254. https://doi.org/10.1021/acsbiomaterials.8b01051

  13. 13.

    Guan X, Li Y, Jiao Z et al (2013) Acta Biomaterialia a pH-sensitive charge-conversion system for doxorubicin delivery. Acta Biomater 9:7672–7678. https://doi.org/10.1016/j.actbio.2013.04.047

  14. 14.

    Lv S, Song W, Tang Z et al Charge-conversional peg-polypeptide polyionic complex nanoparticles from simple blending of a pair of oppositely charged block copolymers as an intelligent vehicle for efficient. Antitumor Drug Deliv. https://doi.org/10.1021/mp4007387

  15. 15.

    Peng S, Men Y, Xie R, Tian Y, Yang W (2019) Journal of colloid and Interface science biodegradable phosphorylcholine-based zwitterionic polymer nanogels with smart charge-conversion ability for efficient inhibition of tumor cells. J Colloid Interface Sci 539:19–29. https://doi.org/10.1016/j.jcis.2018.12.035

  16. 16.

    Xu YS, Wang H, Luan CX et al (2018) Porous hydrogel encapsulated photonic barcodes for multiplex microRNA quantification. Adv Funct Mater 28:1–7. https://doi.org/10.1002/adfm.201704458

  17. 17.

    Kim M, Cha C (2018) Integrative control of mechanical and degradation properties of in situ crosslinkable polyamine-based hydrogels for dual-mode drug release kinetics. Polymer (Guildf) 145:272–280. https://doi.org/10.1016/j.polymer.2018.05.020

  18. 18.

    Dan K, Ghosh S (2014) Stimuli responsive triblock copolymers by chain-growth polymerization from telechelic macroinitiators prepared via a step-growth polymerization. Polym Chem 5:3901–3909. https://doi.org/10.1039/c4py00078a

  19. 19.

    Huang Y, Sun R, Luo Q et al (2016) In situ fabrication of paclitaxel-loaded core-crosslinked micelles via thiol-ene “click” chemistry for reduction-responsive drug release. J Polym Sci Part A Polym Chem 54:99–107. https://doi.org/10.1002/pola.27778

  20. 20.

    Liu Y, Chen J, Tang Y, Li S, Dou Y, Zheng J (2018) Synthesis and characterization of quaternized poly(β-amino ester) for highly efficient delivery of small interfering RNA. Mol Pharm 15:4558–4567. https://doi.org/10.1021/acs.molpharmaceut.8b00549

  21. 21.

    Capasso Palmiero U, Kaczmarek JC, Fenton OS, Anderson DG (2018) Poly(β-amino ester)-co-poly(caprolactone) terpolymers as nonviral vectors for mRNA delivery in vitro and in vivo. Adv Healthc Mater 7:1–6. https://doi.org/10.1002/adhm.201800249

  22. 22.

    Feng X, Zhou Y, Xie X, Li M, Huang H, Wang L, Xu X, Yu J (2019) Materials Science & Engineering C Development of PSMA-targeted and core-crosslinked glycol chitosan micelles for docetaxel delivery in prostate cancer therapy. Mater Sci Eng C 96:436–445. https://doi.org/10.1016/j.msec.2018.11.044

  23. 23.

    Lale SV, Kumar A, Naz F, et al (2015) Multifunctional ATRP based pH responsive polymeric nanoparticles for improved doxorubicin chemotherapy in breast cancer by proton sponge effect/endo-lysosomal escape. Polymer Chemistry 6:2115–2132. https://doi.org/10.1039/c4py01698j

  24. 24.

    Xu W, Ding J, Chen X (2017) Reduction-responsive polypeptide micelles for intracellular delivery of antineoplastic agent. Biomacromolecules 18:3291-3301. https://doi.org/10.1021/acs.biomac.7b00950

  25. 25.

    Zhou T, Zhao X, Liu L, Liu P (2015) Preparation of biodegradable PEGylated pH/reduction dual-stimuli responsive nanohydrogels for controlled release of an anti-cancer drug. Nanoscale 7:12051–12060. https://doi.org/10.1039/c5nr00758e

  26. 26.

    Hsieh Y, Hsiao Y, Jan J (2014) Soft Matter 10:9568–9576. https://doi.org/10.1039/C4SM02033B

  27. 27.

    Shi B, Huang K, Ding J, et al (2017) Intracellularly swollen polypeptide nanogel assists hepatoma chemotherapy. Theranostics 7:703–716. https://doi.org/10.7150/thno.16794

  28. 28.

    Zhang L, Zhang P, Zhao Q, Zhang Y, Cao L, Luan Y (2016) Journal of colloid and interface science doxorubicin-loaded polypeptide nanorods based on electrostatic interactions for cancer therapy. J Colloid Interface Sci 464:126–136. https://doi.org/10.1016/j.jcis.2015.11.008

Download references

Author information

Correspondence to Feng Gao.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 611 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Gao, F., Wang, Q. & Yang, X. pH-responsive nanoparticles based on optimized synthetic amphiphilic poly(β-amino esters) for doxorubicin delivery. Colloid Polym Sci (2020). https://doi.org/10.1007/s00396-020-04606-7

Download citation

Keywords

  • Poly(β-amino esters)
  • Charge conversion
  • pH responsiveness
  • Enhanced cellular uptake