Skip to main content

Advertisement

SpringerLink
Log in

Black phosphorus nanosheets and docetaxel micelles co-incorporated thermoreversible hydrogel for combination chemo-photodynamic therapy

  • Original Article
  • Published:
Drug Delivery and Translational Research Aims and scope Submit manuscript

Abstract

The platform of the combination chemo-photodynamic therapy has received widespread attention for enhancing anticancer efficacy and inhibiting tumor growth, which supports thermosensitive and controlled drug release. Here, an injectable thermoreversible hydrogel (BPNSs/DTX-M-hydrogel) co-encapsulating black phosphorus nanosheets (BPNSs) and docetaxel (DTX) micelles was prepared to increase drug accumulation in tumor tissue and improve anticancer efficacy. BPNSs were prepared by liquid exfoliation method with a simple and rapid preparation, and DTX micelles were prepared by the thin film dispersion method. Hydrogel was prepared with F127 as hydrogel matrix for intratumoral injection. BPNSs, DTX micelles, and BPNSs/DTX-M-hydrogel were characterized by particle size, morphology, stability and degradation, phase transition feature, and photodynamic performance. And the in vivo anticancer efficacy was evaluated in 4T1 tumor-bearing Balb/c mice. The results showed that the particle size of DTX micelles and BPNSs were about 16 and 180 nm, respectively. The hydrogel with the transformation temperature at near body exhibited great photodynamic efficacy and good biodegradability. Moreover, BPNSs/DTX-M-hydrogel with the combination of chemotherapy and photodynamic therapy exhibited unique anticancer efficacy with low toxicity. In conclusion, the combination platform of chemo-photodynamic therapy based on BPNSs could be a prospective strategy in antitumor research.

Graphical abstract

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. Sun YB, Ma W, Yang YY, He MX, Li AM, Bai L, et al. Cancer nanotechnology: enhancing tumor cell response to chemotherapy for hepatocellular carcinoma therapy. Asian J Pharm Sci. 2019;14:581–94.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Yu MN, Su DY, Yang YY, Qin L, Hu C, Liu R, et al. D-T7 peptide-modified PEGylated bilirubin nanoparticles loaded with cediranib and paclitaxel for antiangiogenesis and chemotherapy of glioma. ACS Appl Mater Interfaces. 2019;11:176–86.

    Article  CAS  PubMed  Google Scholar 

  3. Fujiki K, Kanayama Y, Yano S, Sato N, Yokokita T, Ahmadi P, et al. 211At-labeled immunoconjugate via a one-pot three-component double click strategy: practical access to a-emission cancer radiotherapeutics. Chem Sci. 2019;10:1936–44.

    Article  CAS  PubMed  Google Scholar 

  4. Korbelik M, Banáth J, Zhang W, Hode T, Lam SSK, Gallagher P, et al. N-Dihydrogalactochitosan-supported tumor control by photothermal therapy and photothermal therapy-generated vaccine. J Photochem Photobiol B. 2020;204:111780.

    Article  CAS  PubMed  Google Scholar 

  5. Chepurna OM, Yakovliev A, Ziniuk R, Nikolaeva OA, Levchenko SM, Xu H, et al. Core-shell polymeric nanoparticles co-loaded with photosensitizer and organic dye for photodynamic therapy guided by fluorescence imaging in near and short-wave infrared spectral regions. J Nanobiotechnol. 2020;18:19.

    Article  CAS  Google Scholar 

  6. Ma W, Sha SN, Chen PL, Yu M, Chen JJ, Huang CB, et al. A cell membrane-targeting self-delivery chimeric peptide for enhanced photodynamic therapy and in situ therapeutic feedback. Adv Healthc Mater. 2020;9:e1901100.

    Article  PubMed  CAS  Google Scholar 

  7. Yu M, Guo F, Wang JP, Tan FP, Li N. A pH-driven and photoresponsive nanocarrier: remotely-controlled by near-infrared light for stepwise antitumor treatment. Biomaterials. 2016;79:25–35.

    Article  CAS  PubMed  Google Scholar 

  8. Ethirajan M, Chen YH, Joshi P, Pandey RK. The role of porphyrin chemistry in tumor imaging and photodynamic therapy. Chem Soc Rev. 2011;40:340–62.

    Article  CAS  PubMed  Google Scholar 

  9. Chilakamarthi U, Giribabu L. Photodynamic therapy: past, present and future. Chem Rec. 2017;17:775–802.

    Article  CAS  PubMed  Google Scholar 

  10. Ge RF, Cao J, Chi JN, Han SC, Liang Y, Xu LS, et al. NIR-guided dendritic nanoplatform for improving antitumor efficacy by combining chemo-phototherapy. Int J Nanomedicine. 2019;14:4931–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lu KD, He CB, Guo NN, Chan C, Ni KY, Weichselbaum RR, et al. Chlorin-based nanoscale metal-organic framework systemically rejects colorectal cancers via synergistic photodynamic therapy and checkpoint blockade immunotherapy. J Am Chem Soc. 2016;138:12502–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lu L, Zhao XJ, Fu TW, Li K, He Y, Luo Z, et al. An iRGD-conjugated prodrug micelle with blood-brain-barrier penetrability for anti-glioma therapy. Biomaterials. 2020;230:119666.

    Article  CAS  PubMed  Google Scholar 

  13. Liu Z, Wang DD, Li JP, Jiang Y. Self-assembled peptido-nanomicelles as an engineered formulation for synergy-enhanced combinational SDT, PDT and chemotherapy to nasopharyngeal carcinoma. Chem Commun. 2019;55:10226–9.

    Article  CAS  Google Scholar 

  14. Zhang D, Zheng AXX, Li J, Wu M, Cai ZX, Wu LJ, et al. Tumor microenvironment activable self-assembled DNA hybrids for pH and redox dual-responsive chemotherapy/PDT treatment of hepatocellular carcinoma. Adv Sci. 2017;4:1600460.

    Article  CAS  Google Scholar 

  15. Zhen SJ, Yi XQ, Zhao ZJ, Lou XD, Xia F, Tang BZ. Drug delivery micelles with efficient near-infrared photosensitizer for combined image-guided photodynamic therapy and chemotherapy of drug-resistant cancer. Biomaterials. 2019;218:119330.

    Article  CAS  PubMed  Google Scholar 

  16. Gulzar A, Xu JT, Xu LG, Yang PP, He F, Yang D, et al. Redox responsive UCNPs-DPA conjugated NGO-PEG-BPEI for cancer theranostic. Dalton Trans. 2018;47:3921–30.

    Article  CAS  PubMed  Google Scholar 

  17. Bharathiraja S, Manivasagan P, Moorthy MS, Bui NQ, Jang B, Phan TTV, et al. Photo-based PDT/PTT dual model killing and imaging of cancer cells using phycocyanin-polypyrrole nanoparticles. Eur J Pharm Biopharm. 2018;123:20–30.

    Article  CAS  PubMed  Google Scholar 

  18. Liu B, Li CX, Chen GY, Liu B, Deng XR, Wei Y, et al. Synthesis and optimization of MoS2@Fe3O4-ICG/Pt(IV) nanoflowers for MR/IR/PA bioimaging and combined PTT/PDT/chemotherapy triggered by 808 nm laser. Adv Sci. 2017;4:1600540.

    Article  CAS  Google Scholar 

  19. Han ST, Hu L, Wang XD, Zhou Y, Zeng YJ, Ruan SC, et al. Black phosphorus quantum dots with tunable memory properties and multilevel resistive switching characteristics. Adv Sci. 2017;4:1600435.

    Article  CAS  Google Scholar 

  20. Li LK, Yu YJ, Ye GJ, Ge QQ, Ou XD, Wu H, et al. Black phosphorus field-effect transistors. Nat Nanotechnol. 2014;9:372–7.

    Article  CAS  PubMed  Google Scholar 

  21. Anju S, Ashtami J, Mohanan PV. Black phosphorus, a prospective graphene substitute for biomedical applications. Mater Sci Eng C Mater Biol Appl. 2019;97:978–93.

    Article  CAS  PubMed  Google Scholar 

  22. Ding HC, Tang ZR, Zhang L, Dong YP. Electrogenerated chemiluminescence of black phosphorus nanosheets and its application in the detection of H2O2. Analyst. 2019;144:1326–33.

    Article  CAS  PubMed  Google Scholar 

  23. Zong SF, Wang LL, Yang ZT, Wang H, Wang ZY, Cui YP. Black phosphorus-based drug nanocarrier for targeted and synergetic chemophotothermal therapy of acute lymphoblastic leukemia. ACS Appl Mater Interfaces. 2019;11:5896–902.

    Article  CAS  PubMed  Google Scholar 

  24. Chen L, Zhong XY, Yi X, Huang M, Ning P, Liu T, et al. Radionuclide 131I labeled reduced graphene oxide for nuclear imaging guided combined radio-and photothermal therapy of cancer. Biomaterials. 2015;66:21–8.

    Article  PubMed  CAS  Google Scholar 

  25. Song GS, Hao JL, Liang C, Liu T, Gao M, Cheng L, et al. Degradable molybdenum oxide nanosheets with rapid clearance and efficient tumor homing capabilities as a therapeutic nanoplatform. Angew Chem Int Ed Engl. 2016;55:2122–6.

    Article  CAS  PubMed  Google Scholar 

  26. Cheng L, Yuan C, Shen S, Yi X, Gong H, Yang K, et al. Bottom-up synthesis of metal-ion-doped WS2 nanoflakes for cancer theranostics. ACS Nano. 2015;9(11):11090–101.

    Article  CAS  PubMed  Google Scholar 

  27. Liu T, Wang C, Gu X, Gong H, Cheng L, Shi XZ, et al. Drug delivery with PEGylated MoS2 nano-sheets for combined photothermal and chemotherapy of cancer. Adv Mater. 2014;26:3433–40.

    Article  PubMed  CAS  Google Scholar 

  28. Chen WS, Ouyang J, Liu H, Chen M, Zeng K, Sheng JP, et al. Black phosphorus nanosheet-based drug delivery system for synergistic photodynamic/photothermal/chemotherapy of cancer. Adv Mater. 2017;29.

  29. Yang XY, Wang DY, Shi YH, Zou JH, Zhao QS, Zhang Q, et al. Black phosphorus nanosheets immobilizing Ce6 for imaging-guided photothermal/photodynamic cancer therapy. ACS Appl Mater Interfaces. 2018;18(10):12431–40.

    Article  CAS  Google Scholar 

  30. Shao JD, Ruan CS, Xie HH, Li ZB, Wang HY, Chu PK, et al. Black-phosphorus-incorporated hydrogel as a sprayable and biodegradable photothermal platform for postsurgical treatment of cancer. Adv Sci (Weinh). 2018;3(5):1700848.

    Article  CAS  Google Scholar 

  31. Wang H, Yang XZ, Shao W, Chen SC, Xie JF, Zhang XD, et al. Ultrathin black phosphorus nanosheets for efficient singlet oxygen generation. J Am Chem Soc. 2015;9(137):11376–82.

    Article  CAS  Google Scholar 

  32. Chen L, Chen C, Chen W, Li K, Chen XZ, Tang XD, et al. Biodegradable black phosphorus nanosheets mediate specific delivery of hTERT siRNA for synergistic cancer therapy. ACS Appl Mater Interfaces. 2018;10:21137–48.

    Article  CAS  PubMed  Google Scholar 

  33. Tan E, Li BL, Ariga K, Lim CT, Garaj S, Leong DT. Toxicity of two-dimensional layered materials and their heterostructures. Bioconjug Chem. 2019;30:2287–99.

    Article  CAS  PubMed  Google Scholar 

  34. Shafei A, El-Bakly W, Sobhy A, Wagdy O, Reda A, Aboelenin O, et al. A review on the efficacy and toxicity of different doxorubicin nanoparticles for targeted therapy in metastatic breast cancer. Biomed Pharmacother. 2017;95:1209–18.

    Article  CAS  PubMed  Google Scholar 

  35. Li N, Xie X, Hu YX, He HD, Fu X, Fang TT, et al. Herceptin-conjugated liposomes co-loaded with doxorubicin and simvastatin in targeted prostate cancer therapy. Am J Transl Res. 2019;11:1255–69.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Wu JL, Zhang HY, Hu X, Liu RL, Jiang W, Li ZH, et al. Reduction-sensitive mixed micelles assembled from amphiphilic prodrugs for self-codelivery of DOX and DTX with synergistic cancer therapy. Colloids Surf B Biointerfaces. 2018;161:449–56.

    Article  CAS  PubMed  Google Scholar 

  37. Yang MY, He SL, Fan YZ, Wang YL, Ge ZZ, Shan L, et al. Microenvironmental pH-modified solid dispersions to enhance the dissolution and bioavailability of poorly water-soluble weakly basic GT0918, a developing anti-prostate cancer drug: preparation, characterization and evaluation in vivo. Int J Pharm. 2014;475:97–109.

    Article  CAS  PubMed  Google Scholar 

  38. Xu M, Mou YH, Hu MM, Dong WX, Su XT, Wu RX, et al. Evaluation of micelles incorporated into thermosensitive hydrogels for intratumoral delivery and controlled release of docetaxel: a dual approach for in situ treatment of tumors. Asian J Pharm Sci. 2018;13:373–82.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Zhang N, Xu XF, Zhang X, Qu D, Xue LG, Mo R, et al. Nanocomposite hydrogel incorporating gold nanorods and paclitaxel-loaded chitosan micelles for combination photothermal-chemotherapy. Int J Pharm. 2016;497:210–21.

    Article  CAS  PubMed  Google Scholar 

  40. Huang PS, Song HJ, Zhang YM, Liu JJ, Cheng Z, Liang XJ, et al. FRET-enabled monitoring of the thermosensitive nanoscale assembly of polymeric micelles into macroscale hydrogel and sequential cognate micelles release. Biomaterials. 2017;145:81–91.

    Article  CAS  PubMed  Google Scholar 

  41. Duan YW, Wang J, Yang XY, Du HL, Xi YW, Zhai GX. Curcumin-loaded mixed micelles: preparation, optimization, physicochemical properties and cytotoxicity in vitro. Drug Deliv. 2015;22:50–7.

    Article  CAS  PubMed  Google Scholar 

  42. Zhang F, Peng FF, Qin L, Yang DD, Li RR, Jiang SS, et al. pH/near infrared dual-triggered drug delivery system based black phosphorus nanosheets for targeted cancer chemo-photothermal therapy. Colloids Surf B Biointerfaces. 2019;180:353–61.

    Article  CAS  PubMed  Google Scholar 

  43. Qin L, Ling GX, Peng FF, Zhang F, Jiang SS, He HY, et al. Black phosphorus nanosheets and gemcitabine encapsulated thermo-sensitive hydrogel for synergistic photothermal-chemotherapy. J Colloid Interface Sci. 2019;556:232–8.

    Article  CAS  PubMed  Google Scholar 

  44. Ding PG, Chen YX, Cao GS, Shen HX, Ju JM, Li WG. Solutol®HS15+pluronicF127 and Solutol®HS15+pluronicL61 mixed micelle systems for oral delivery of genistein. Drug Des Dev Ther. 2019;13:1947–56.

    Article  CAS  Google Scholar 

  45. Liu LM, Liu M, Wilkinson DM, Chen HH, Yu XQ, Yang J. DNA metabarcoding reveals that 200-μm-size-fractionated filtering is unable to discriminate between planktonic microbial and large eukaryotes. Mol Ecol Resour. 2017;17:991–1002.

    Article  CAS  PubMed  Google Scholar 

  46. Silva DRG, Holman BWB, Kerr MJ, Morris S, Ramos EM, Hopkins DL. Effect of homogenisation speed and centrifugation on particle size analysis of beef and the relationship with shear force. Meat Sci. 2018;143:219–22.

    Article  PubMed  Google Scholar 

  47. Thi TD, Van Speybroeck M, Barillaro V, Martens J, Annaert P, Augustijns P, et al. Formulate-ability of ten compounds with different physicochemical profiles in SMEDDS. Eur J Pharm Sci. 2009;38:479–88.

    Article  CAS  PubMed  Google Scholar 

  48. Blankenship-Paris TL, Dutton JW, Goulding DR, McGee CA, Kissling GE, Myers PH. Evaluation of buprenorphine hydrochloride Pluronic® gel formulation in male C57BL/6NCrl mice. Res Note. 2016;45:370–9.

    Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China (81202480, 81302723) and Natural Science Foundation of Liaoning Province (2015020749).

Author information

Authors and Affiliations

  1. Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China

    Ruirui Li, Linwei Shan, Yanan Yao, Feifei Peng, Shanshan Jiang, Dandan Yang, Guixia Ling & Peng Zhang

Authors
  1. Ruirui Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Linwei Shan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yanan Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Feifei Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shanshan Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dandan Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Guixia Ling
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Peng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peng Zhang.

Ethics declarations

Declaration of interest

The authors declare that they have no conflict of interest.

Animal studies

This article contained animal studies; all institutional and national guidelines for the care and use of laboratory animals were followed. The animal studies were permitted by the Animal Ethics Committee of Shenyang Pharmaceutical University (Shenyang, China). Animal studies were conducted according to the “guidelines for the care and use of laboratory.” The living conditions of the animals were appropriate for their species and contribute to their health and comfort. Normally, the housing, feeding, and care of all animals used for biomedical purposes were directed by other scientist trained and experienced in the proper care, handling, and use of the species being studied. The use of animals was proper including the avoidance or minimization of discomfort, distress, and pain when consistent with sound scientific practices. Procedures with animals that might cause more than momentary or slight pain or distress were performed with appropriate sedation, analgesia, or anesthesia. The procedures were not performed on un-anesthetized animals paralyzed by chemical agents. Animals were painlessly euthanized at the end of the procedure. The animal studies were harmless to humans or the environment.

Ethical statement

We certify that this manuscript is original and has not been published and will not be submitted elsewhere for publication while being considered by DDTR. And the study is not split up into several parts to increase the quantity of submissions and submitted to various journals or to one journal over time. No data have been fabricated or manipulated (including images) to support our conclusions. Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, R., Shan, L., Yao, Y. et al. Black phosphorus nanosheets and docetaxel micelles co-incorporated thermoreversible hydrogel for combination chemo-photodynamic therapy. Drug Deliv. and Transl. Res. 11, 1133–1143 (2021). https://doi.org/10.1007/s13346-020-00836-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13346-020-00836-y

Keywords

Search

Navigation