As a synthetic clay material, laponite RDS (LR) was investigated as an effective drug carrier as a result of the special nanodisk structure together with the negative-charged surface to achieve enhanced cellular uptake and targeted delivery. In this research work, the synthesized oligomeric hyaluronic acid-aminophenylboronic acid (oHA-APBA) was entangled onto LR nanodisks to fabricate a valid targeted platform for breast cancer therapy. Briefly, through the formation of amide bonds, 3-APBA was connected to the chain of oHA with a substituted ratio of 4.0 ± 0.2% to synthesize oHA-APBA copolymer. Thereafter, doxorubicin (DOX) was inserted into the interlayer space of LR by the way of the ion exchange process, followed by an assembly with oHA-APBA as a targeted protection layer. The satisfactory drug encapsulation efficiency (> 80%) and narrow size distribution were achieved. The in vitro drug release study demonstrated the release of DOX from DOX@LR/oHA-APBA was sustained and acid dependent. In addition, after fitting the drug cumulative release of DOX@LR/oHA-APBA under different pH conditions with several kinetic models, it was identified that drug release from DOX@LR/oHA-APBA nanohybrids at pH 5.0 was mainly dependent on both diffusion and ion exchange effects. However, under the condition of pH 7.4, the drug was most efficiently released by diffusion effect. Importantly, DOX@LR/oHA-APBA showed remarkable cellular uptake and intracellular drug distribution in MCF-7 cells, which were consistent with inhibitory ability against MCF-7 cells. Hence, the high DOX loading capacity and enhanced cellular tracking can enlighten LR/oHA-APBA as an effective drug delivery carrier for breast cancer therapy.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Wei L, Chen J, Zhao S, Ding J, Chen X. Thermo-sensitive polypeptide hydrogel for locally sequential delivery of two-pronged antitumor drugs. Acta Biomater. 2017;58:44–53. https://doi.org/10.1016/j.actbio.2017.05.053.
Li D, Feng X, Chen L, Ding J, Chen X. One-step synthesis of targeted acid-labile polysaccharide prodrug for efficiently intracellular drug delivery. ACS Biomater Sci Eng. 2018;4(2):539–46. https://doi.org/10.1021/acsbiomaterials.7b00856.
Zhang X, Liang N, Gong X, Kawashima Y, Cui F, Sun S. Tumor-targeting micelles based on folic acid and alpha-tocopherol succinate conjugated hyaluronic acid for paclitaxel delivery. Colloids Surf B: Biointerfaces. 2019;177:11–8. https://doi.org/10.1016/j.colsurfb.2019.01.044.
Lee JY, Termsarasab U, Park JH, Lee SY, Ko SH, Shim JS, et al. Dual CD44 and folate receptor-targeted nanoparticles for cancer diagnosis and anticancer drug delivery. J Control Release. 2016;236:38–46. https://doi.org/10.1016/j.jconrel.2016.06.021.
Jia X, Han Y, Pei M, Zhao X, Tian K, Zhou T, et al. Multi-functionalized hyaluronic acid nanogels crosslinked with carbon dots as dual receptor-mediated targeting tumor theranostics. Carbohydr Polym. 2016;152:391–7. https://doi.org/10.1016/j.carbpol.2016.06.109.
Zhang X, Zhang Z, Su X, Cai M, Zhuo R, Zhong Z. Phenylboronic acid-functionalized polymeric micelles with a HepG2 cell targetability. Biomaterials. 2013;34(38):10296–304. https://doi.org/10.1016/j.biomaterials.2013.09.042.
Low PS, Henne WA, Doorneweerd DD. Discovery and development of folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases. Acc Chem Res. 2008;41(1):120–9. https://doi.org/10.1002/chin.200818242.
Chung YI, Kim JC, Kim YH, Tae G, Lee SY, Kim K, et al. The effect of surface functionalization of PLGA nanoparticles by heparin- or chitosan-conjugated Pluronic on tumor targeting. J Control Release. 2010;143(3):374–82. https://doi.org/10.1016/j.jconrel.2010.01.017.
Ravar F, Saadat E, Gholami M, Dehghankelishadi P, Mahdavi M, Azami S, et al. Hyaluronic acid-coated liposomes for targeted delivery of paclitaxel, in-vitro characterization and in-vivo evaluation. J Control Release. 2016;229:10–22. https://doi.org/10.1016/j.jconrel.2016.03.012.
Li D, Zhang YT, Yu M, Guo J, Chaudhary D, Wang CC. Cancer therapy and fluorescence imaging using the active release of doxorubicin from MSPs/Ni-LDH folate targeting nanoparticles. Biomaterials. 2013;34(32):7913–22. https://doi.org/10.1016/j.biomaterials.2013.06.046.
Liu ZL, Tian DY, Li SP, Li XD, Lu TH. MTX/LDHs hybrids synthesized from reverse microemulsions: particle control and bioassay study. Int J Pharm. 2014;473(1–2):414–25. https://doi.org/10.1016/j.ijpharm.2014.07.044.
Rojas R, Giacomelli CE. Size-tunable LDH–protein hybrids toward the optimization of drug nanocarriers. J Mater Chem B. 2015;3(14):2778–85. https://doi.org/10.1039/c4tb01992j.
Ley C, Brendle J, Walter A, Jacques P, Ibrahim A, Allonas X. On the interaction of triarylmethane dye crystal violet with LAPONITE® clay: using mineral nanoparticles to control the dye photophysics. Phys Chem Chem Phys. 2015;17(26):16677–81. https://doi.org/10.1039/c5cp02370j.
Chen G, Li D, Li J, Cao X, Wang J, Shi X, et al. Targeted doxorubicin delivery to hepatocarcinoma cells by lactobionic acid-modified laponite nanodisks. New J Chem. 2015;39(4):2847–55. https://doi.org/10.1039/c4nj01916d.
Wang Je WG, Sun Y, Wang Y, Yang Y, Yuan Y, et al. In situ formation of pH−/thermo-sensitive nanohybrids via friendly-assembly of poly(N-vinylpyrrolidone) onto LAPONITE®. RSC Adv. 2016;6(38):31816–23. https://doi.org/10.1039/c5ra25628c.
Jung H, Kim HM, Choy YB, Hwang SJ, Choy JH. Laponite-based nanohybrid for enhanced solubility and controlled release of itraconazole. Int J Pharm. 2008;349(1–2):283–90. https://doi.org/10.1016/j.ijpharm.2007.08.008.
Jung H, Kim HM, Choy YB, Hwang SJ, Choy JH. Itraconazole–Laponite: kinetics and mechanism of drug release. Appl Clay Sci. 2008;40(1–4):99–107. https://doi.org/10.1016/j.clay.2007.09.002.
Wang S, Zheng F, Huang Y, Fang Y, Shen M, Zhu M, et al. Encapsulation of amoxicillin within laponite-doped poly(lactic-co-glycolic acid) nanofibers: preparation, characterization, and antibacterial activity. ACS Appl Mater Interfaces. 2012;4(11):6393–401. https://doi.org/10.1021/am302130b.
Chen X, Wang Y, Chai R, Xu Y, Li H, Liu B. Luminescent lanthanide-based organic/inorganic hybrid materials for discrimination of glutathione in solution and within hydrogels. ACS Appl Mater Interfaces. 2017;9(15):13554–63. https://doi.org/10.1021/acsami.7b02679.
Felbeck T, Behnke T, Hoffmann K, Grabolle M, Lezhnina MM, Kynast UH, et al. Nile-red-nanoclay hybrids: red emissive optical probes for use in aqueous dispersion. Langmuir. 2013;29(36):11489–97. https://doi.org/10.1021/la402165q.
Grabolle M, Starke M, Resch-Genger U. Highly fluorescent dye-nanoclay hybrid materials made from different dye classes. Langmuir. 2016;32(14):3506–13. https://doi.org/10.1021/acs.langmuir.5b04297.
Deng C, Zhang Q, Fu Y, Sun X, Gong T, Zhang Z. Coadministration of oligomeric hyaluronic acid-modified liposomes with tumor-penetrating peptide-iRGD enhances the antitumor efficacy of doxorubicin against melanoma. ACS Appl Mater Interfaces. 2017;9(2):1280–92. https://doi.org/10.1021/acsami.6b13738.
Lv S, Li M, Tang Z, Song W, Sun H, Liu H, et al. Doxorubicin-loaded amphiphilic polypeptide-based nanoparticles as an efficient drug delivery system for cancer therapy. Acta Biomater. 2013;9(12):9330–42. https://doi.org/10.1016/j.actbio.2013.08.015.
Ahmad N, Ahmad R, Alam MA, Ahmad FJ. Enhancement of oral bioavailability of doxorubicin through surface modified biodegradable polymeric nanoparticles. Chem Cent J. 2018;12(1):65. https://doi.org/10.1186/s13065-018-0434-1.
Li JY, Yue Y, Yu YB, Li Q, Tan GX, Wang YY, et al. Laponite nanoplatform functionalized with histidine modified oligomeric hyaluronic acid as an effective vehicle for anticancer drug methotrexate. J Mater Chem B. 2018;6(30):5011–20. https://doi.org/10.1039/C8TB01284A.
Song Y, Cai H, Yin T, Huo M, Ma P, Zhou J, et al. Paclitaxel-loaded redox-sensitive nanoparticles based on hyaluronic acid-vitamin E succinate conjugates for improved lung cancer treatment. Int J Nanomedicine. 2018;13:1585–600. https://doi.org/10.2147/ijn.s155383.
Chen D, Lian S, Sun J, Liu Z, Zhao F, Jiang Y, et al. Design of novel multifunctional targeting nano-carrier drug delivery system based on CD44 receptor and tumor microenvironment pH condition. Drug Deliv. 2016;23(3):808–13. https://doi.org/10.3109/10717544.2014.917130.
Dosio F, Arpicco S, Stella B, Fattal E. Hyaluronic acid for anticancer drug and nucleic acid delivery. Adv Drug Deliv Rev. 2016;97:204–36. https://doi.org/10.1016/j.addr.2015.11.011.
Jeong JY, Hong EH, Lee SY, Lee JY, Song JH, Ko SH, et al. Boronic acid-tethered amphiphilic hyaluronic acid derivative-based nanoassemblies for tumor targeting and penetration. Acta Biomater. 2017;53:414–26. https://doi.org/10.1016/j.actbio.2017.02.030.
Geninatti Crich S, Alberti D, Szabo I, Aime S, Djanashvili K. MRI visualization of melanoma cells by targeting overexpressed sialic acid with a Gd(III)-dota-en-pba imaging reporter. Angew Chem. 2013;52(4):1161–4. https://doi.org/10.1002/anie.201207131.
Ahmad N, Alam MA, Ahmad R, Naqvi AA, Ahmad FJ. Preparation and characterization of surface-modified PLGA-polymeric nanoparticles used to target treatment of intestinal cancer. Artif Cells Nanomed Biotechnol. 2018;46(2):432–46. https://doi.org/10.1080/21691401.2017.1324466.
Ahmad N, Alam MA, Ahmad R, Umar S, Jalees Ahmad F. Improvement of oral efficacy of irinotecan through biodegradable polymeric nanoparticles through in vitro and in vivo investigations. J Microencapsul. 2018;35(4):327–43. https://doi.org/10.1080/02652048.2018.1485755.
Ahmad N, Ahmad R, Alam MA, Ahmad FJ, Amir M, Pottoo FH, et al. Daunorubicin oral bioavailability enhancement by surface coated natural biodegradable macromolecule chitosan based polymeric nanoparticles. Int J Biol Macromol. 2019;128:825–38. https://doi.org/10.1016/j.ijbiomac.2019.01.142.
Li X, Xing L, Hu Y, Xiong Z, Wang R, Xu X, et al. An RGD-modified hollow silica@Au core/shell nanoplatform for tumor combination therapy. Acta Biomater. 2017;62:273–83. https://doi.org/10.1016/j.actbio.2017.08.024.
Alam MA, Ahmad N, Ahmad R, Talegaonkar S, Ahmad FJ, Iqbal Z, et al. Quantification of tamoxifen polymeric nanoparticles in female rodent breast tissue by UPLC/ESI-Q-TOF MS/MS. J Young Pharm. 2016;8(4):415–23. https://doi.org/10.5530/jyp.2016.4.18.
Ahmad J, Ahmad N, Kohli K, Mir S, Amin S. Pharmacokinetic analysis of taxane through a validated ultra-high performance liquid chromatography-synapt mass spectrometry (UHPLC-MS/MS ESI-Q-TOF) method. Curr Bioact Compd. 2016;12(2):93–102. https://doi.org/10.2174/157340721202160504222440.
Wang S, Wu Y, Guo R, Huang Y, Wen S, Shen M, et al. Laponite nanodisks as an efficient platform for doxorubicin delivery to cancer cells. Langmuir. 2013;29(16):5030–6. https://doi.org/10.1021/la4001363.
Wu Y, Guo R, Wen S, Shen M, Zhu M, Wang J, et al. Folic acid-modified laponite nanodisks for targeted anticancer drug delivery. J Mater Chem B. 2014;2(42):7410–8. https://doi.org/10.1039/c4tb01162g.
This work was supported by the National Natural Science Foundation Youth Science Foundation Project (81703709) and project funded by China Postdoctoral Science Foundation (2018M641716).
Conflict of Interest
The authors declare that they have no conflict of interest.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Yang, Y., Li, J., Chen, F. et al. Synthesis, Formulation, and Characterization of Doxorubicin-Loaded Laponite/Oligomeric Hyaluronic Acid-Aminophenylboronic Acid Nanohybrids and Cytological Evaluation against MCF-7 Breast Cancer Cells. AAPS PharmSciTech 21, 5 (2020). https://doi.org/10.1208/s12249-019-1533-6
- laponite RDS
- targeted delivery
- oligomeric hyaluronic acid
- 3-aminophenylboronic acid
- breast cancer therapy