The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers
Source abstract
Abstract
Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability and a high capacity for disparate cargos. Here we report porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma exhibit a 10,000-fold greater affinity for human hepatocellular carcinoma than for hepatocytes, endothelial cells or immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, small interfering RNA and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer enable a single protocell loaded with a drug cocktail to kill a drug-resistant human hepatocellular carcinoma cell, representing a 10(6)-fold improvement over comparable liposomes.
Source: europepmc · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Nanoparticle-Based Drug Delivery · RNA Interference and Gene Delivery · Advanced biosensing and bioanalysis techniques
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (53)
Show source-provided references
1. Peer, D. et al. Nanocarriers as an emerging platform for cancer therapy. Nature Nanotech. 2, 751–760 (2007).10.1038/nnano.2007.387 ↗
2. Wagner, V., Dullaart, A., Bock, A-K. & Zweck, A. The emerging nanomedicine landscape. Nature Biotechnol. 24, 1211–1217 (2006).10.1038/nbt1006-1211 ↗
3. Nel, A. E. et al. Understanding biophysicochemical interactions at the nano–bio interface. Nature Mater. 8, 543–557 (2009).10.1038/nmat2442 ↗
4. Ferrari, M. Cancer nanotechnology: Opportunities and challenges. Nature Rev. Cancer 5, 161–171 (2005).
5. Maeda, H., Wu, J., Sawa, T., Matsumura, Y. & Hori, K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: A review. J. Control. Release 65, 271–284 (2000).10.1016/S0168-3659(99)00248-5 ↗
6. Matsumura, Y. & Maeda, H. A new concept for macromolecular therapeutics in cancer chemotherapy: Mechanism of tumoritropic accumulation of proteins and the antitumour agent SMANCS. Cancer Res. 46, 6387–6392 (1986).
7. Gottesman, M. M., Fojo, T. & Bates, S. E. Multidrug resistance in cancer: Role of ATP-dependent transporters. Nature Rev. Cancer 2, 48–58 (2002).10.1038/nrc706 ↗
8. Kohlschütter, J., Michelfelder, S. & Trepel, M. Drug delivery in acute myeloid leukemia. Expert Opin. Drug Deliv. 5, 653–663 (2008).10.1517/17425247.5.6.653 ↗
9. Torchilin, V. P. Recent advances with liposomes as pharmaceutical carriers. Nature Rev. Drug Discov. 4, 145–160 (2005).10.1038/nrd1632 ↗
10. Rai, P. et al. Statistical pattern matching facilitates the design of polyvalent inhibitors of anthrax and cholera toxins. Nature Biotechnol. 24, 582–586 (2006).10.1038/nbt1204 ↗
11. Jiang, W., Kim, B. Y. S., Rutka, J. T. & Chan, W. C. W. Nanoparticle-mediated cellular response is size-dependent. Nature Nanotech. 3, 145–150 (2008).10.1038/nnano.2008.30 ↗
12. Pastan, I., Hassan, R., FitzGerald, D. J. & Kreitman, R. J. Immunotoxin therapy of cancer. Nature Rev. Cancer 6, 559–565 (2006).10.1038/nrc1891 ↗
13. Ferrari, M. Nanogeometry: Beyond drug delivery. Nature Nanotech. 3, 131–132 (2008).10.1038/nnano.2008.46 ↗
14. Giri, S., Trewyn, B. G., Stellmaker, M. P. & Lin, V. S. Y. Stimuli-responsive controlled-release delivery system based on mesoporous silica nanorods capped with magnetic nanoparticles. Angew. Chem. Int. Ed. 44, 5038–5044 (2005).10.1002/anie.200501819 ↗
15. Lai, C-Y. et al. A mesoporous silica nanosphere-based carrier system with chemically removable CdS nanoparticle caps for stimuli-responsive controlled release of neurotransmitters and drug molecules. J. Am. Chem. Soc. 125, 4451–4459 (2003).10.1021/ja028650l ↗
16. Liong, M. et al. Multifunctional inorganic nanoparticles for imaging, targeting, and drug delivery. ACS Nano 2, 889–896 (2008).10.1021/nn800072t ↗
17. Nguyen, T. D. et al. A reversible molecular valve. Proc. Natl Acad. Sci. USA 102, 10029–10034 (2005).10.1073/pnas.0504109102 ↗
18. Patel, K. et al. Enzyme-responsive snap-top covered silica nanocontainers. J. Am. Chem. Soc. 130, 2382–2383 (2008).10.1021/ja0772086 ↗
19. Vallet-Regı´, M., Balas, F. & Arcos, D. Mesoporous materials for drug delivery. Angew. Chem. Int. Ed. 46, 7548–7558 (2007).10.1002/anie.200604488 ↗
20. Davis, M. E., Chen, Z. & Shin, D. M. Nanoparticle therapeutics: An emerging treatment modality for cancer. Nature Rev. Drug Discov. 7, 771–782 (2008).10.1038/nrd2614 ↗
21. Gordon, A. N. et al. Recurrent epithelial ovarian carcinoma: A randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J. Clin. Oncol. 19, 3312–3322 (2001).10.1200/JCO.2001.19.14.3312 ↗
22. Peer, D., Zhu, P., Carman, C. V., Lieberman, J. & Shimaoka, M. Selective gene silencing in activated leukocytes by targeting siRNAs to the integrin lymphocyte function-associated antigen-1. Proc. Natl Acad. Sci. USA 104, 4095–4100 (2007).10.1073/pnas.0608491104 ↗
23. Liu, J. W., Jiang, X. M., Ashley, C. & Brinker, C. J. Electrostatically mediated liposome fusion and lipid exchange with a nanoparticle-supported bilayer for control of surface charge, drug containment, and delivery. J. Am. Chem. Soc. 131, 7567–7569 (2009).10.1021/ja902039y ↗
24. Liu, J. W., Stace-Naughton, A. & Brinker, C. J. Silica nanoparticle supported lipid bilayers for gene delivery. Chem. Commun. 5100–5102 (2009).10.1039/b911472f ↗
25. Liu, J. W., Stace-Naughton, A., Jiang, X. M. & Brinker, C. J. Porous nanoparticle supported lipid bilayers (protocells) as delivery vehicles. J. Am. Chem. Soc. 131, 1354–1355 (2009).10.1021/ja808018y ↗
26. Lu, Y. F. et al. Aerosol-assisted self-assembly of mesostructured spherical nanoparticles. Nature 398, 223–226 (1999).10.1038/18410 ↗
27. Evans, E. Entropy-driven tension in vesicle membranes and unbinding of adherent vesicles. Langmuir 7, 1900–1908 (1991).10.1021/la00057a014 ↗
28. Komura, S., Shimokawa, N. & Andelman, D. Tension-induced morphological transition in mixed lipid bilayers. Langmuir 22, 6771–6774 (2006).10.1021/la053135x ↗
29. Lipowsky, R. The conformation of membranes. Nature 349, 475–481 (1991).10.1038/349475a0 ↗
30. Mutz, M. & Helfrich, W. Unbinding transition of a biological model membrane. Phys. Rev. Lett. 62, 2881–2884 (1989).10.1103/PhysRevLett.62.2881 ↗
31. Netz, R. R. & Lipowsky, R. Stacks of fluid membranes under pressure and tension. Europhys. Lett. 29, 345–350 (1995).10.1209/0295-5075/29/4/013 ↗
32. Swain, P. S. & Andelman, D. Supported membranes on chemically structured and rough surfaces. Phys. Rev. E 63, 051911 (2001).10.1103/PhysRevE.63.051911 ↗
33. Bothun, G. D., Knutson, B. L., Strobel, H. J. & Nokes, S. E. Liposome fluidization and melting point depression by pressurized CO2 determined by fluorescence anisotropy. Langmuir 21, 530–536 (2004).10.1021/la0496542 ↗
34. Doshi, D. A. et al. Neutron reflectivity study of lipid membranes assembled on ordered nanocomposite and nanoporous silica thin films. Langmuir 21, 2865–2870 (2005).10.1021/la0471240 ↗
35. Daillant, J. et al. Structure and fluctuations of a single floating lipid bilayer. Proc. Natl Acad. Sci. USA 102, 11639–11644 (2005).10.1073/pnas.0504588102 ↗
36. Malaquin, L., Charitat, T. & Daillant, J. Supported bilayers: Combined specular and diffuse X-ray scattering. Eur. Phys. J. E 31, 285–301 (2010).10.1140/epje/i2010-10578-2 ↗
37. Huang, S-C. J. et al. Formation, stability, and mobility of one-dimensional lipid bilayers on polysilicon nanowires. Nano Lett. 7, 3355–3359 (2007).10.1021/nl071641w ↗
38. Swain, P. S. & Andelman, D. The influence of substrate structure on membrane adhesion. Langmuir 15, 8902–8914 (1999).10.1021/la990503m ↗
39. Lo, A., Lin, C. T. & Wu, H. C. Hepatocellular carcinoma cell-specific peptide ligand for targeted drug delivery. Mol. Cancer Therapeut. 7, 579–589 (2008).10.1158/1535-7163.MCT-07-2359 ↗
40. Chen, Z. et al. DNA translocation through an array of kinked nanopores. Nature Mater. 9, 667–675 (2010).10.1038/nmat2805 ↗
41. Lu, Y. F. et al. Continuous formation of supported cubic and hexagonal mesoporous films by sol gel dip-coating. Nature 389, 364–368 (1997).10.1038/38699 ↗
42. Goren, D. et al. Nuclear delivery of doxorubicin via folate-targeted liposomes with bypass of multidrug-resistance efflux pump. Clin. Cancer Res. 6, 1949–1957 (2000).
43. Midoux, P., Kichler, A., Boutin, V., Maurizot, J-C. & Monsigny, M. Membrane permeabilization and efficient gene transfer by a peptide containing several histidines. Bioconjug. Chem. 9, 260–267 (1998).10.1021/bc9701611 ↗
44. Behr, J. P. The proton sponge: A trick to enter cells the viruses did not exploit. CHIMIA Int. J. Chem. 51, 34–36 (1997).10.2533/chimia.1997.34 ↗
45. Subramanian, A., Ranganathan, P. & Diamond, S. L. Nuclear targeting peptide scaffolds for lipofection of nondividing mammalian cells. Nature Biotechnol. 17, 873–877 (1999).10.1038/12860 ↗
46. Fritze, A., Hens, F., Kimpfler, A., Schubert, R. & Peschka-Süss, R. Remote loading of doxorubicin into liposomes driven by a transmembrane phosphate gradient. Biochim. Biophys. Acta Biomembr. 1758, 1633–1640 (2006).10.1016/j.bbamem.2006.05.028 ↗
47. Drummond, D. C., Meyer, O., Hong, K., Kirpotin, D. B. & Papahadjopoulos, D. Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors. Pharmacol. Rev. 51, 691–744 (1999).10.1016/S0031-6997(24)01426-1 ↗
48. Lee, J. O. et al. Combination chemotherapy with capecitabine and cisplatin for patients with metastatic hepatocellular carcinoma. Ann. Oncol. 20, 1402–1407 (2009).10.1093/annonc/mdp010 ↗
49. Khalil, I. A., Kogure, K. & Futaki, S. High density of octaarginine stimulates macropinocytosis leading to efficient intracellular trafficking for gene expression. J. Biol. Chem. 281, 3544–3551 (2006).10.1074/jbc.M503202200 ↗
50. Carroll, N. J., Pylypenko, S., Atanassov, P. B. & Petsev, D. N. Microparticles with bimodal nanoporosity derived by microemulsion templating. Langmuir 25, 13540–13544 (2009).10.1021/la900988j ↗
51. Xia, T. et al. Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties. ACS Nano 2, 2121–2134 (2008).10.1021/nn800511k ↗
52. Elorza, B., Elorza, M. A., Frutos, G. & Chantres, J. R. Characterization of 5-fluorouracil loaded liposomes prepared by reverse-phase evaporation or freezing–thawing extrusion methods: Study of drug release. Biochim. et Biophys. Acta 1153, 135–142 (1993).10.1016/0005-2736(93)90398-J ↗
53. Peleg-Shulman, T., Gibson, D., Cohen, R., Abra, R. & Barenholz, Y. Characterization of sterically stabilized cisplatin liposomes by nuclear magnetic resonance. Biochim. Biophys. Acta 1510, 278–291 (2001).10.1016/S0005-2736(00)00359-X ↗