Skip to main content
SpringerLink
Log in

Synthesis, Characterization of NR@SiO2/PNIPAm-co-Ppa Composite Nanogel and Study On Its Application in Photodynamic Therapy

  • Original Article
  • Published:
Journal of Fluorescence Aims and scope Submit manuscript

Abstract

In the present study, a novel composite nanogel based on fluorescence resonance energy transfer (FRET) and its application for photodynamic therapy is reported. First of all, nanoparticles of silica doped with Nile Red (NR) were prepared by Stöber method, then they were decorated by γ-methacryloxypropyltrimethoxysilane (MPS) to prepare MPS decorated NR@SiO2 nanoparticles, and finally they were copolymerized with N-isopropylacrylamide (NIPAm) and Pyropheophorbide-a (Ppa) by free radical copolymerization, and composite nanogel of NR@SiO2/PNIPAm-co-Ppa was fabricated. The microstructure of the as-prepared nanogel was characterized by Fourier transform infrared spectrum (FTIR), photoluminescence (PL), UV–Visible spectrophotometer (UV–Vis), dynamic light scattering (DLS) and transmission electron microscopy (TEM). PL spectrum indicated that, under irradiation of visible light source, energy can be transferred from NR to Ppa. UV–Vis spectrum demonstrated that aggregation of Ppa is prevented efficiently and Ppa exists as “monomer” state in the composite nanogel. Under irradiation of laser, singlet oxygen (1O2) can be produced efficiently by excited nanogel. The in vitro cytotoxicity test showed that HeLa cells can be killed by the composite nanogel.

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

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code Availability

Not applicable.

References

  1. Li XS, Lee SY, Yoon JY (2018) Supramolecular photosensitizers rejuvenate photodynamic therapy. Chem Soc Rev 47:1174–1188. https://doi.org/10.1039/c7cs00594f

    Article  CAS  PubMed  Google Scholar 

  2. Lan GX, Ni KY, Xu ZW, Veroneau SS, Song Y, Lin WB (2018) A Nanoscale Metal-Organic Framework Overcomes Hypoxia for Photodynamic Therapy Primed Cancer Immunotherapy. J Am Chem Soc 140:5670–5673. https://doi.org/10.1021/jacs.8b01072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Fan WP, Huang P, Chen XY (2016) Overcoming the Achilles’ heel of photodynamic therapy. Chem Soc Rev 45:6488–6519. https://doi.org/10.1039/c6cs00616g

    Article  CAS  PubMed  Google Scholar 

  4. Chen JM, Fan TJ, Xie ZJ, Zeng QQ, Xue P, Zheng TT, Chen Y, Luo XL, Zhang H (2020) Advances in nanomaterials for photodynamic therapy applications: Status and challenges. Biomaterials 237:119827. https://doi.org/10.1016/j.biomaterials.2020.119827

    Article  CAS  PubMed  Google Scholar 

  5. Lismont M, Dreesen L, Wuttke S (2017) Metal-organic framework nanoparticles in photodynamic therapy: current status and perspectives. Adv Funct Mater 27:1606314. https://doi.org/10.1002/adfm.201606314

    Article  CAS  Google Scholar 

  6. Kim J, Cho HR, Jeon H, Kim D, Song C, Lee N, Choi SH, Hyeon T (2017) Continuous O2-evolving MnFe2O4 nanoparticle-anchored mesoporous silica nanoparticles for efficient photodynamic therapy in hypoxic cancer. J Am Chem Soc 139:10992–10995. https://doi.org/10.1021/jacs.7b05559

    Article  CAS  PubMed  Google Scholar 

  7. Ma CA, Shi LL, Huang Y, Shen LY, Peng H, Zhu XY, Zhou GY (2017) Nanoparticle delivery of Wnt-1 siRNA enhances photodynamic therapy by inhibiting epithelial-mesenchymal transition for oral cancer. Biomater Sci 5:494–501. https://doi.org/10.1039/c6bm00833j

    Article  CAS  PubMed  Google Scholar 

  8. Ishida N, Osawa S, Miyazu T, Kaneko M, Tamura S, Tani S, Yamade M, Iwaizumi M, Hamaya Y, Furuta T, Sugimoto K (2020) Photodynamic Therapy Using Talaporfin Sodium for Local Failure after Chemoradiotherapy or Radiotherapy for Esophageal Cancer: A Single Center Experience. J Clin Med 9:1509. https://doi.org/10.3390/jcm9051509

    Article  CAS  PubMed Central  Google Scholar 

  9. Ha JH, Kim YJ (2021) Photodynamic and Cold Atmospheric Plasma Combination Therapy Using Polymeric Nanoparticles for the Synergistic Treatment of Cervical Cancer. Int J Mol Sci 22:1172. https://doi.org/10.3390/ijms22031172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Cheng JJ, Tan GH, Li WT, Zhang HY, Wu XD, Wang ZQ, Jin YX (2016) Facile synthesis of chitosan assisted multifunctional magnetic Fe3O4@SiO2@CS@pyropheophorbide-a fluorescent nanoparticles for photodynamic therapy. New J Chem 40:8522–8534. https://doi.org/10.1039/c6nj01765g

    Article  CAS  Google Scholar 

  11. Wang J, Liu Q, Zhang YT, Shi H, Liu H, Guo WJ, Ma YH, Huang WQ, Hong ZY (2017) Folic acid conjugated pyropheophorbide a as the photosensitizer tested for in vivo targeted photodynamic therapy. J Pharm Sci 106:1482–1489. https://doi.org/10.1016/j.xphs.2017.02.019

    Article  CAS  PubMed  Google Scholar 

  12. Xiong HJ, Yan JH, Cai SD, He QY, Wen NC, Wang Y, Hu YQ, Peng DM, Liu YF, Liu ZB (2020) Aptamer-Pyropheophorbide a Conjugates with Tumor Spheroid Targeting and Penetration Abilities for Photodynamic Therapy. Mol Pharmaceutics 17:2882–2890. https://doi.org/10.1021/acs.molpharmaceut.0c00335

    Article  CAS  Google Scholar 

  13. Rossi LM, Silva PR, Vono LLR, Fernandes AU, Tada DB, Baptista MS (2008) Protoporphyrin IX nanoparticle carrier: preparation, optical properties, and singlet oxygen generation. Langmuir 24:12534–12538. https://doi.org/10.1021/la800840k

    Article  CAS  PubMed  Google Scholar 

  14. Liang DL, Song QS, Yao YT, Liu B (2019) Preparation of Complex Nanogel with Up-conversion Fluorescence-responsive Performance and Its Fluorescence Energy Transfer Behavior. Chem J Chin Univ 40:583–591. https://doi.org/10.7503/cjcu20180470

    Article  CAS  Google Scholar 

  15. Chapman G, Patonay G (2019) NIR-Fluorescent Multidye Silica Nanoparticles with Large Stokes Shifts for Versatile Biosensing Applications. J Fluoresc 29:293–305. https://doi.org/10.1007/s10895-018-02339-z

    Article  CAS  PubMed  Google Scholar 

  16. Algar WR, Hildebrandt N, Vogel SS, Medintz IL (2019) FRET as a biomolecular research tool-understanding its potential while avoiding pitfalls. Nat Methods 16:815–829. https://doi.org/10.1038/s41592-019-0530-8

    Article  CAS  PubMed  Google Scholar 

  17. Zhou B, Yan DP (2019) Hydrogen-Bonded Two-Component Ionic Crystals Showing Enhanced Long-Lived Room-Temperature Phosphorescence via TADF-Assisted Förster Resonance Energy Transfer. Adv Funct Mater 29:1807599. https://doi.org/10.1002/adfm.201807599

    Article  CAS  Google Scholar 

  18. Huang CB, Xu L, Zhu JL, Wang YX, Sun B, Li XP, Yang HB (2017) Real-time monitoring the dynamics of coordination-driven self-assembly by fluorescence-resonance energy transfer. J Am Chem Soc 139:9459–9462. https://doi.org/10.1021/jacs.7b04659

    Article  CAS  PubMed  Google Scholar 

  19. Chen LY, Tse WH, Chen Y, McDonald MW, Melling J, Zhang J (2017) Nanostructured biosensor for detecting glucose in tear by applying fluorescence resonance energy transfer quenching mechanism. Biosens Bioelectron 5:393–399. https://doi.org/10.1016/j.bios.2016.12.044

    Article  CAS  Google Scholar 

  20. Ge MH, Sun JJ, Chen ML, Tian JJ, Yin HC, Yin J (2020) A hyaluronic acid fluorescent hydrogel based on fluorescence resonance energy transfer for sensitive detection of hyaluronidase. Anal Bioanal Chem 412:1915–1923. https://doi.org/10.1007/s00216-020-02443-9

    Article  CAS  PubMed  Google Scholar 

  21. Ikeda M, Fukuda K, Tanida T, Yoshii T, Hamachi I (2012) A supramolecular hydrogel containing boronic acid-appended receptor for fluorocolorimetric sensing of polyols with a paper platform. Chem Commun 48:2716–2718. https://doi.org/10.1039/C2CC17503G

    Article  CAS  Google Scholar 

  22. Yu YL, Zhang MJ, Xie R, Ju XJ, Wang JY, Pi SW, Chu LY (2012) Thermo-responsive monodisperse core-shell microspheres with PNIPAM core and biocompatible porous ethyl cellulose shell embedded with PNIPAM gates. J Colloid Interface Sci 376:97–106. https://doi.org/10.1016/j.jcis.2012.03.028

    Article  CAS  PubMed  Google Scholar 

  23. Yuan S, Ge FY, Yang X, Guang SY (2016) Self-Assembly of Colloidal Photonic Crystals of PS@PNIPAM Nanoparticles and Temperature-Responsive Tunable Fluorescence. J Fluoresc 26:1–8. https://doi.org/10.1016/j.jlumin.2012.12.005

    Article  CAS  Google Scholar 

  24. Ma B, Ju XJ, Luo F, Liu YQ, Wang Y, Liu Z, Wang W, Xie R, Chu LY (2017) Facile Fabrication of Composite Membranes with Dual Thermo- and pH-Responsive Characteristics. ACS Appl Mater Interfaces 9:14409–14421. https://doi.org/10.1021/acsami.7b02427

    Article  CAS  PubMed  Google Scholar 

  25. Stöber W, Fink A, Bohn E (1968) Controlled growth of monodisperse silica spheres in the micron size range. J Colloid Interface Sci 26:62–69. https://doi.org/10.1016/0021-9797(68)90272-5

    Article  Google Scholar 

  26. Tada DB, Vono LLR, Duarte EL, Itri R, Kiyohara PK, Baptista MS, Rossi LM (2007) Methylene blue-containing silica-coated magnetic particles: A potential magnetic carrier for photodynamic therapy. Langmuir 23:8194–8199. https://doi.org/10.1021/la700883y

    Article  CAS  PubMed  Google Scholar 

  27. Korínek M, Dědic R, Molnár A, Svoboda A, Hála J (2005) A comparison of photosensitizing properties of meso-tetraphenylporphin in acetone and in dimethyl sulfoxide. J Mol Struct 744:727–731. https://doi.org/10.1016/j.molstruc.2004.11.036

    Article  CAS  Google Scholar 

  28. Wang HW, Cheng HR, Wang FQ, Wei DZ, Wang XD (2010) An improved 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction assay for evaluating the viability of Escherichia coli cells. J Microbiol Methods 82:330–333. https://doi.org/10.1016/j.mimet.2010.06.014

    Article  CAS  PubMed  Google Scholar 

  29. Jhonsi MA, Nithya C, Kathiravan A (2017) Unravel the interaction of protoporphyrin IX with reduced graphene oxide by vital spectroscopic techniques. Spectrochim Acta Part A 178:86–93. https://doi.org/10.1016/j.saa.2017.01.059

    Article  CAS  Google Scholar 

  30. Wang TT, Ke HZ, Chen SP, Wang J, Yang WS, Cao XM, Liu JY, Wei QF, Ghiladi RA, Wang QQ (2021) Porous protoporphyrin IX-embedded cellulose diacetate electrospun microfibers in antimicrobial photodynamic inactivation. Mater Sci Eng C 118:111502. https://doi.org/10.1016/j.msec.2020.111502

    Article  CAS  Google Scholar 

  31. Zhang QC, Song QS, Zhang ZW, Zhao CY, Ma HH (2020) Preparation, self-assembly of SiO2/PNIPAm complex microgels and their manipulation of fluorescence emission for organic dyes. Colloid Polym Sci 298:1587–1596. https://doi.org/10.1007/s00396-020-04746-w

    Article  CAS  Google Scholar 

  32. Ravichandiran P, Boguszewska-Czubara A, Maslyk M, Bella AP, Johnson PM, Subramaniyan SA, Shim KS, Yoo DJ (2020) A phenoxazine-based fluorescent chemosensor for dual channel detection of Cd2+ and CN ions and its application to bio-imaging in live cells and zebrafish. Dyes Pigm 172:107828. https://doi.org/10.1016/j.dyepig.2019.107828

    Article  CAS  Google Scholar 

  33. Tzounis L, Doña M, Lopez-Romero JM, Fery A, Contreras-Caceres R (2019) Temperature-Controlled Catalysis by Core-Shell-Satellite AuAg@pNIPAM@Ag Hybrid Microgels: A Highly Efficient Catalytic Thermoresponsive Nanoreactor. ACS Appl Mater Interfaces 11:29360–29372. https://doi.org/10.1021/acsami.9b10773

    Article  CAS  PubMed  Google Scholar 

  34. Hornum M, Reinholdt P, Zareba JK, Jensen BB, Wustner D, Samoc M, Nielsen P, Kongsted J (2020) One- and two-photon solvatochromism of the fluorescent dye Nile Red and its CF3, F and Br-substituted analogues. Photochem Photobiol Sci 19:1382–1391. https://doi.org/10.1039/D0PP00076K

    Article  CAS  PubMed  Google Scholar 

  35. Seo J, Jang J, Warnke S, Gewinner S, Schollkopf W, von Helden G (2016) Stacking Geometries of Early Protoporphyrin IX Aggregates Revealed by Gas-Phase Infrared Spectroscopy. J Am Chem Soc 138:16315–16321. https://doi.org/10.1021/jacs.6b08700

    Article  CAS  PubMed  Google Scholar 

  36. Scolaro LM, Castriciano M, Romeo A, Patanè S, Cefalì E, Allegrini M (2002) Aggregation Behavior of Protoporphyrin IX in Aqueous Solutions: Clear Evidence of Vesicle Formation. J Phys Chem B 106:2453–2459. https://doi.org/10.1021/jp013155h

    Article  CAS  Google Scholar 

  37. Gouterman M (1959) Study of the Effects of Substitution on the Absorption Spectra of Porphin. J Chem Phys 30:1139–1161. https://doi.org/10.1063/1.1730148

    Article  CAS  Google Scholar 

  38. Gouterman M (1961) Spectra of porphyrins. J Mol Spectrosc 6:138–163. https://doi.org/10.1016/0022-2852(61)90236-3

    Article  CAS  Google Scholar 

  39. Hornum M, Mulberg MW, Szomek M, Reinholdt P, Brewer JR, Wustner D, Kongsted J, Nielsen P (2020) Substituted 9-Diethylaminobenzo [a] phenoxazin-5-ones (Nile Red Analogues): Synthesis and Photophysical Properties. J Org Chem 86:1471–1488. https://doi.org/10.1021/acs.joc.0c02346

  40. Lim WQ, Yang G, Phua SZF, Chen HZ, Zhao YL (2019) Self-Assembled Oxaliplatin (IV) Prodrug-Porphyrin Conjugate for Combinational Photodynamic and Chemotherapy. ACS Appl Mater Interfaces 11:16391–16401. https://doi.org/10.1021/acsami.9b04557

    Article  CAS  PubMed  Google Scholar 

  41. Rajora MA, Lou J, Zheng G (2017) Advancing porphyrin’s biomedical utility via supramolecular chemistry. Chem Soc Rev 46:6433–6469. https://doi.org/10.1039/c7cs00525c

    Article  CAS  PubMed  Google Scholar 

  42. Qi JP, Hu XW, Dong XC, Lu Y, Lu HP, Zhao WL, Wu W (2019) Towards more accurate bioimaging of drug nanocarriers: turning aggregation-caused quenching into a useful tool. Adv Drug Delivery Rev 143:206–225. https://doi.org/10.1016/j.addr.2019.05.009

    Article  CAS  Google Scholar 

  43. Sheng N, Zong SF, Cao W, Jiang JZ, Wang ZY, Cui YP (2015) Water Dispersible and Biocompatible Porphyrin-Based Nanospheres for Biophotonics Applications: A Novel Surfactant and Polyelectrolyte-Based Fabrication Strategy for Modifying Hydrophobic Porphyrins. ACS Appl Mater Interfaces 7:19718–19725. https://doi.org/10.1021/acsami.5b05256

    Article  CAS  PubMed  Google Scholar 

  44. Schild HG (1992) Poly(N-isopropylacrylamide): experiment, theory and application. Prog Polym Sci 17:163–249. https://doi.org/10.1016/0079-6700(92)90023-R

    Article  CAS  Google Scholar 

Download references

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. School of Chemistry and Chemical Engineering, Hefei University of Technology, Hefei, 230009, P. R. China

    Zirui Wang, Qiusheng Song, Lin Zhu, Chengyan Zhao & Haihong Ma

Authors
  1. Zirui Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qiusheng Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lin Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chengyan Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Haihong Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Zirui Wang, Qiusheng Song, Lin Zhu, Chengyan Zhao, and Haihong Ma. The first draft of the manuscript was written by Zirui Wang and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Qiusheng Song.

Ethics declarations

Ethics Approval

Not applicable.

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Conflicts 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.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOC 430 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Z., Song, Q., Zhu, L. et al. Synthesis, Characterization of NR@SiO2/PNIPAm-co-Ppa Composite Nanogel and Study On Its Application in Photodynamic Therapy. J Fluoresc 32, 771–782 (2022). https://doi.org/10.1007/s10895-021-02872-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10895-021-02872-4

Keywords

Search

Navigation