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Development of NIR-II fluorescence image-guided and pH-responsive nanocapsules for cocktail drug delivery

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Abstract

Nanocapsule-based targeted delivery and stimulus-responsive release can increase drug effectiveness, while reducing the side effects of the drug. However, difficulties in the scale-up synthesis, fast burst release, and low degradability, could hamper the translation of drug nanocapsules from lab to clinic. Here we have controllably functionalized the biodegradable and widely available polysuccinimide, in order to obtain an amphiphilic poly(amino acid). Using this polymer, we designed nanocapsules (< 100 nm) for hydrophobic drug delivery, which could facilitate tumor targeting, hydrogen bond-based pH-responsive release, and real-time fluorescence tracking, in the second near-infrared region. This method is versatile, eco-friendly, and easy to scale up at low costs. In addition, this system can carry a cocktail of drugs, obtained by loading multiple anticancer drugs to the same vehicle. Our nanocapsules were observed to be stable in blood vessels (pH = 7.4), and the pH-responsive release (pH = 5.0 in lysosome) was sustained. The chemotherapy results in tumor-xenografted mice suggested that our nanocapsule was safe and efficient, and may be a useful tool for drug delivery.

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References

  1. Sugano, K.; Kansy, M.; Artursson, P.; Avdeef, A.; Bendels, S.; Di, L.; Ecker, G. F.; Faller, B.; Fischer, H.; Gerebtzoff, G. et al. Coexistence of passive and carrier-mediated processes in drug transport. Nat. Rev. Drug Discovery 2010, 9, 597–614.

    Article  Google Scholar 

  2. Petros, R. A.; DeSimone, J. M. Strategies in the design of nanoparticles for therapeutic applications. Nat. Rev. Drug Discovery 2010, 9, 615–627.

    Article  Google Scholar 

  3. Fu, J. L.; Yan, H. Controlled drug release by a nanorobot. Nat. Biotechnol. 2012, 30, 407–408.

    Article  Google Scholar 

  4. MacKay, J. A.; Chen, M. N.; McDaniel, J. R.; Liu, W. G.; Simnick, A. J.; Chilkoti, A. Self-assembling chimeric polypeptide-doxorubicin conjugate nanoparticles that abolish tumours after a single injection. Nat. Mater. 2009, 8, 993–999.

    Article  Google Scholar 

  5. Kong, G.; Braun, R. D.; Dewhirst, M. W. Hyperthermia enables tumor-specific nanoparticle delivery: Effect of particle size. Cancer Res. 2000, 60, 4440–4445.

    Google Scholar 

  6. Mura, S.; Nicolas, J.; Couvreur, P. Stimuli-responsive nanocarriers for drug delivery. Nat. Mater. 2013, 12, 991–1003.

    Article  Google Scholar 

  7. Kearney, C. J.; Mooney, D. J. Macroscale delivery systems for molecular and cellular payloads. Nat. Mater. 2013, 12, 1004–1017.

    Article  Google Scholar 

  8. Stuart, M. A. C.; Huck, W. T. S.; Genzer, J.; Muller, M.; Ober, C.; Stamm, M.; Sukhorukov, G. B.; Szleifer, I.; Tsukruk, V. V.; Urban, M. et al. Emerging applications of stimuli-responsive polymer materials. Nat. Mater. 2010, 9, 101–113.

    Article  Google Scholar 

  9. Lee, T. K.; Sokoloski, T. D.; Royer, G. P. Serum albumin beads: An injectable, biodegradable system for the sustained release of drugs. Science 1981, 213, 233–235.

    Article  Google Scholar 

  10. Zhou, C.; Hao, G. Y.; Thomas, P.; Liu, J. B.; Yu, M. X.; Sun, S. S.; Öz, O. K.; Sun, X. K.; Zheng, J. Near-infrared emitting radioactive gold nanoparticles with molecular pharmacokinetics. Angew. Chem. Int. Ed. 2012, 51, 10118–10122.

    Article  Google Scholar 

  11. Choi, H. S.; Ipe, B. I.; Misra, P.; Lee, J. H.; Bawendi, M. G.; Frangioni, J. V. Tissue- and organ-selective biodistribution of NIR fluorescent quantum dots. Nano Lett. 2009, 9, 2354–2359.

    Article  Google Scholar 

  12. Prescott, J. H.; Lipka, S.; Baldwin, S.; Sheppard, N. F.; Maloney, J. M.; Coppeta, J.; Yomtov, B.; Staples, M. A.; Santini, J. T. Chronic, programmed polypeptide delivery from an implanted, multireservoir microchip device. Nat. Biotechnol. 2006, 24, 437–438.

    Article  Google Scholar 

  13. Gref, R.; Minamitake, Y.; Peracchia, M. T.; Trubetskoy, V.; Torchilin, V.; Langer, R. Biodegradable long-circulating polymeric nanospheres. Science 1994, 263, 1600–1603.

    Article  Google Scholar 

  14. Namgung, R.; Lee, Y. M.; Kim, J.; Jang, Y.; Lee, B. H.; Kim, I. S.; Sokkar, P.; Rhee, Y. M.; Hoffman, A. S.; Kim, W. J. Poly-cyclodextrin and poly-paclitaxel nano-assembly for anticancer therapy. Nat. Commun. 2014, 5, 4702–4713.

    Article  Google Scholar 

  15. Cui, J. W.; Yan, Y.; Wang, Y. J.; Caruso, F. Templated sssembly of pH-labile polymer-drug particles for intracellular drug delivery. Adv. Funct. Mater. 2012, 22, 4718–4723.

    Article  Google Scholar 

  16. Yan, Y.; Wang, Y. J.; Heath, J. K.; Nice, E. C.; Caruso, F. Cellular association and cargo release of redox-responsive polymer capsules mediated by exofacial thiols. Adv. Mater. 2011, 23, 3916–3921.

    Article  Google Scholar 

  17. Liu, Z.; Fan, A. C.; Rakhra, K.; Sherlock, S.; Goodwin, A.; Chen, X. Y.; Yang, Q. W.; Felsher, D. W.; Dai, H. J. Supramolecular stacking of doxorubicin on carbon nanotubes for in vivo cancer therapy. Angew. Chem. Int. Ed. 2009, 48, 7668–7672.

    Article  Google Scholar 

  18. Peng, F.; Su, Y. Y.; Wei, X. P.; Lu, Y. M.; Zhou, Y. F.; Zhong, Y. L.; Lee, S. T.; He, Y. Silicon-nanowire-based nanocarriers with ultrahigh drug-loading capacity for in vitro and in vivo cancer therapy. Angew. Chem. Int. Ed. 2013, 52, 1457–1461.

    Article  Google Scholar 

  19. Wang, Y. H.; Xu, Z. H.; Guo, S. T.; Zhang, L.; Sharma, A.; Robertson, G. P.; Huang, L. Intravenous delivery of siRNA targeting CD47 effectively inhibits melanoma tumor growth and lung metastasis. Mol. Ther. 2013, 21, 1919–1929.

    Article  Google Scholar 

  20. Wang, Q. L.; Zhuang, X. Y.; Mu, J. Y.; Deng, Z. B.; Jiang, H.; Zhang, L. F.; Xiang, X. Y.; Wang, B. M.; Yan, J.; Miller, D. et al. Delivery of therapeutic agents by nanoparticles made of grapefruit-derived lipids. Nat. Commun. 2013, 4, 2886–2896.

    Google Scholar 

  21. Santra, S.; Kaittanis, C.; Santiesteban, O. J.; Perez, J. M. Cell-specific, activatable, and theranostic prodrug for dual-targeted cancer imaging and therapy. J. Am. Chem. Soc. 2011, 133, 16680–16688.

    Article  Google Scholar 

  22. Du, J. Z.; Du, X. J.; Mao, C. Q.; Wang, J. Tailor-made dual pH-sensitive polymer-doxorubicin nanoparticles for efficient anticancer drug delivery. J. Am. Chem. Soc. 2011, 133, 17560–17563.

    Article  Google Scholar 

  23. Ellis, G. A.; Palte, M. J.; Raines, R. T. Boronate-mediated biologic delivery. J. Am. Chem. Soc. 2012, 134, 3631–3634.

    Article  Google Scholar 

  24. Chen, W.; Meng, F. H.; Li, F.; Ji, S. J.; Zhong, Z. Y. pH-responsive biodegradable micelles based on acid-labile polycarbonate hydrophobe: Synthesis and triggered drug release. Biomacromolecules 2009, 10, 1727–1735.

    Article  Google Scholar 

  25. Kolano, C.; Helbing, J.; Kozinski, M.; Sander, W.; Hamm, P. Watching hydrogen-bond dynamics in a beta-turn by transient two-dimensional infrared spectroscopy. Nature 2006, 444, 469–472.

    Article  Google Scholar 

  26. Zhang, J.; Chen, P. C.; Yuan, B. K.; Ji, W.; Cheng, Z. H.; Qiu, X. H. Real-space identification of intermolecular bonding with atomic force microscopy. Science 2013, 342, 611–614.

    Article  Google Scholar 

  27. Takahara, P. M.; Rosenzweig, A. C.; Frederick, C. A.; Lippard, S. J. Crystal structure of double-stranded DNA containing the major adduct of the anticancer drug cisplatin. Nature 1995, 377, 649–652.

    Article  Google Scholar 

  28. Prota, A. E.; Bargsten, K.; Zurwerra, D.; Field, J. J.; Díaz, J. F.; Altmann, K. H.; Steinmetz, M. O. Molecular mechanism of action of microtubule-stabilizing anticancer agents. Science 2013, 339, 587–590.

    Article  Google Scholar 

  29. Kim, B. S.; Park, S. W.; Hammond, P. T. Hydrogen-bonding layer-by-layer assembled biodegradable polymeric micelles as drug delivery vehicles from surfaces. ACS Nano 2008, 2, 386–392.

    Article  Google Scholar 

  30. Ma, M. L.; Kuang, Y.; Gao, Y.; Zhang, Y.; Gao, P.; Xu, B. Aromatic-aromatic interactions induce the self-assembly of pentapeptidic derivatives in water to form nanofibers and supramolecular hydrogels. J. Am. Chem. Soc. 2010, 132, 2719–2728.

    Article  Google Scholar 

  31. Xing, B. G.; Yu, C. W.; Chow, K. H.; Ho, P. L.; Fu, D. G.; Xu, B. Hydrophobic interaction and hydrogen bonding cooperatively confer a vancomycin hydrogel: A potential candidate for biomaterials. J. Am. Chem. Soc. 2002, 124, 14846–14847.

    Article  Google Scholar 

  32. Pasparakis, G.; Manouras, T.; Vamvakaki, M.; Argitis, P. Harnessing photochemical internalization with dual degradable nanoparticles for combinatorial photo-chemotherapy. Nat. Commun. 2014, 5, 4623–4631.

    Article  Google Scholar 

  33. Mikhaylov, G.; Mikac, U.; Magaeva, A. A.; Itin, V. I.; Naiden, E. P.; Psakhye, I.; Babes, L.; Reinheckel, T.; Peters, C.; Zeiser, R. et al. Ferri-liposomes as an MRI-visible drug-delivery system for targeting tumours and their microenvironment. Nat. Nanotechnol. 2011, 6, 594–602.

    Article  Google Scholar 

  34. Kaittanis, C.; Shaffer, T. M.; Ogirala, A.; Santra, S.; Perez, J. M.; Chiosis, G.; Li, Y. M.; Josephson, L.; Grimm, J. Environment-responsive nanophores for therapy and treatment monitoring via molecular MRI quenching. Nat. Commun. 2014, 5, 4384–4394.

    Article  Google Scholar 

  35. Horcajada, P.; Chalati, T.; Serre, C.; Gillet, B.; Sebrie, C.; Baati, T.; Eubank, J. F.; Heurtaux, D.; Clayette, P.; Kreuz, C. et al. Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging. Nat. Mater. 2010, 9, 172–178.

    Article  Google Scholar 

  36. Wang, H. J.; Wang, L. Y. One-pot syntheses and cell imaging applications of poly(amino acid) coated LaVO4:Eu3+ luminescent nanocrystals. Inorg. Chem. 2013, 52, 2439–2445.

    Article  Google Scholar 

  37. Wang, L. Y.; Zhang, Y.; Zhu, Y. Y. One-pot synthesis and strong near-infrared upconversion luminescence of poly(acrylic acid)-functionalized YF3:Yb3+/Er3+ nanocrystals. Nano Res. 2010, 3, 317–325.

    Article  Google Scholar 

  38. Deng, M. L.; Ma, Y. X.; Huang, S.; Hu, G. F.; Wang, L. Y. Monodisperse upconversion NaYF4 nanocrystals: Syntheses and bioapplications. Nano Res. 2011, 4, 685–694.

    Article  Google Scholar 

  39. Deng, M. L.; Tu, N. N.; Bai, F.; Wang, L. Y. Surface functionalization of hydrophobic nanocrystals with one particle per micelle for bioapplications. Chem. Mater. 2012, 24, 2592–2597.

    Article  Google Scholar 

  40. Deng, M. L.; Wang, L. Y. Unexpected luminescence enhancement of upconverting nanocrystals by cation exchange with well retained small particle size. Nano Res. 2014, 7, 782–793.

    Article  Google Scholar 

  41. Li, H.; Wang, L. Y. Controllable multicolor upconversion luminescence by tuning the NaF dosage. Chem. -Asian J. 2014, 9, 153–157.

    Article  Google Scholar 

  42. Li, H.; Wang, L. Y. Preparation and upconversion luminescence cell imaging of O-carboxymethyl chitosan-functionalized NaYF4:Yb3+/Tm3+/Er3+ nanoparticles. Chin. Sci. Bull. 2013, 58, 4051–4056.

    Article  Google Scholar 

  43. Huang, S.; Bai, M.; Wang, L. Y. General and facile surface functionalization of hydrophobic nanocrystals with poly(amino acid) for cell luminescence imaging. Sci. Rep. 2013, 3, 2023–2027.

    Google Scholar 

  44. Peer, D.; Karp, J. M.; Hong, S.; FaroKhzad, O. C.; Margalit, R.; Langer, R. Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotechnol. 2007, 2, 751–760.

    Article  Google Scholar 

  45. Hong, G. S.; Robinson, J. T.; Zhang, Y. J.; Diao, S.; Antaris, A. L.; Wang, Q. B.; Dai, H. J. In vivo fluorescence imaging with Ag2S quantum dots in the second near-infrared region. Angew. Chem. Int. Ed. 2012, 51, 9818–9821.

    Article  Google Scholar 

  46. Jiang, P.; Tian, Z. Q.; Zhu, C. N.; Zhang, Z. L.; Pang, D. W. Emission-tunable near-infrared Ag2S quantum dots. Chem. Mat. 2012, 24, 3–5.

    Article  Google Scholar 

  47. Du, Y. P.; Xu, B.; Fu, T.; Cai, M.; Li, F.; Zhang, Y.; Wang, Q. B. Near-infrared photoluminescent Ag2S quantum dots from a single source precursor. J. Am. Chem. Soc. 2010, 132, 1470–1471.

    Article  Google Scholar 

  48. Yi, H. J.; Ghosh, D.; Ham, M. H.; Qi, J. F.; Barone, P. W.; Strano, M. S.; Belcher, A. M. M13 phage-functionalized single-walled carbon nanotubes as nanoprobes for second near-infrared window fluorescence imaging of targeted tumors. Nano Lett. 2012, 12, 1176–1183.

    Article  Google Scholar 

  49. Tu, N. N.; Wang, L. Y. Surface plasmon resonance enhanced upconversion luminescence in aqueous media for TNT selective detection. Chem. Commun. 2013, 49, 6319–6321.

    Article  Google Scholar 

  50. Hu, S. H.; Chen, S. Y.; Gao, X. H. Multifunctional nanocapsules for simultaneous encapsulation of hydrophilic and hydrophobic compounds and on-demand release. ACS Nano 2012, 6, 2558–2565.

    Article  Google Scholar 

  51. Ruoslahti, E.; Pierschbacher, M. D. New perspectives in cell adhesion: RGD and integrins. Science 1987, 238, 491–497.

    Article  Google Scholar 

  52. Balasubramanian, S. V.; Straubinger, R. M. Taxol-lipid interactions: Taxol-dependent effects on the physical properties of model membranes. Biochemistry 1994, 33, 8941–8947.

    Article  Google Scholar 

  53. Lv, P. P.; Ma, Y. F.; Yu, R.; Yue, H.; Ni, D. Z.; Wei, W.; Ma, G. H. Targeted delivery of insoluble cargo (paclitaxel) by PEGylated chitosan nanoparticles grafted with Arg-Gly-Asp (RGD). Mol. Pharmaceutics 2012, 9, 1736–1747.

    Article  Google Scholar 

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Huang, S., Peng, S., Li, Y. et al. Development of NIR-II fluorescence image-guided and pH-responsive nanocapsules for cocktail drug delivery. Nano Res. 8, 1932–1943 (2015). https://doi.org/10.1007/s12274-015-0702-5

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  • DOI: https://doi.org/10.1007/s12274-015-0702-5

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