Noncovalent Functionalization of Carbon Nanovectors with an Antibody Enables Targeted Drug Delivery
Source abstract
Abstract
Current chemotherapeutics are characterized by efficient tumor cell-killing and severe side effects mostly derived from off-target toxicity. Hence targeted delivery of these drugs to tumor cells is actively sought. We previously demonstrated that poly(ethylene glycol)-functionalized carbon nanovectors are able to sequester paclitaxel, a widely used hydrophobic cancer drug, by simple physisorption and thereby deliver the drug for killing of cancer cells. The cell-killing when these drug-loaded carbon nanoparticles were used was equivalent to when a commercial formulation of paclitaxel was used. Here we show that by further mixing the drug-loaded nanoparticles with Cetuximab, a monoclonal antibody that recognizes the epidermal growth factor receptor (EGFR), paclitaxel is preferentially targeted to EGFR+ tumor cells in vitro. This supports progressing to in vivo studies. Moreover, the construct is unusual in that all three components are assembled through noncovalent interactions. Such noncovalent assembly could enable high-throughput screening of drug/antibody combinations.
Source: openalex_inverted_index · Quality: baseline
Research context
OpenAlex topics: Graphene and Nanomaterials Applications · Carbon Nanotubes in Composites · Nanoparticle-Based Drug Delivery
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Chemistry and the ‡Smalley Institute for Nanoscale Science and Technology, Rice University, MS-222, 6100 Main Street, Houston, Texas 77005, United States
Department of Head and Neck Surgery, Unit 441, and the ⊥Department of Experimental Therapeutics, Unit 1950, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, United States.
References (30)
Show source-provided references
1. O’Driscoll C. M. · Adv. Drug Delivery Rev. · 2008 · 60 · 61710.1016/j.addr.2007.10.012 ↗
2. Stinchcombe T. E. · Nanomedicine · 2007 · 2 · 41510.2217/17435889.2.4.415 ↗
3. Gradishar W. J. · J. Clin. Oncol. · 2005 · 23 · 779410.1200/JCO.2005.04.937 ↗
4. Gursoy N. · J. Pharm. Sci. · 2003 · 92 · 241110.1002/jps.10501 ↗
5. Chen H. M. · Pharm. Res. · 2003 · 20 · 130210.1023/A:1025021603288 ↗
6. Crosasso P. · J. Controlled Release · 2000 · 63 · 1910.1016/S0168-3659(99)00166-2 ↗
7. Shuai X. T. · Bioconjugate Chem. · 2004 · 15 · 44110.1021/bc034113u ↗
8. Ruan G. · Biomaterials · 2003 · 24 · 503710.1016/S0142-9612(03)00419-8 ↗
9. Ferrari M. · Nat. Rev. Cancer · 2005 · 5 · 16110.1038/nrc1566 ↗
10. Riehemann K. · Angew. Chem., Int. Ed. · 2009 · 48 · 87210.1002/anie.200802585 ↗
11. Berlin J. M. · ACS Nano · 2010 · 4 · 462110.1021/nn100975c ↗
12. Berlin, J. M.; Pham, T. T.; Marcano, D. C.; Sano, D.; Lu, W.; Myers, J. N.; Tour, J. M.In VitroDrug Delivery of Unmodified Paclitaxel Non-covalently Loaded on Carbon Nanovectors of Diverse Shape and Composition.Chem. Mater. 2011, in press.
13. Peer D. · Nat. Nanotechnol. · 2007 · 2 · 75110.1038/nnano.2007.387 ↗
14. Alley S. C. · Curr. Opin. Chem. Biol. · 2010 · 14 · 52910.1016/j.cbpa.2010.06.170 ↗
15. Fay F. · Immunotherapy · 2011 · 3 · 38110.2217/imt.11.5 ↗
16. Bonner J. A. · J. Clin. Oncol. · 2000 · 18 · 47s
17. Grandis J. R. · J. Natl. Cancer Inst. · 1998 · 90 · 82410.1093/jnci/90.11.824 ↗
18. Bonner J. A. · Int. J. Radiat. Oncol. · 1994 · 29 · 24310.1016/0360-3016(94)90269-0 ↗
19. Huang S. M. · Cancer Res. · 1999 · 59 · 1935
20. Saleh M. N. · Cancer Biother. Radiopharm. · 1999 · 14 · 451
21. Vermorken J. B. · N. Engl. J. Med. · 2008 · 359 · 111610.1056/NEJMoa0802656 ↗
22. Bonner J. A. · N. Engl. J. Med. · 2006 · 354 · 56710.1056/NEJMoa053422 ↗
23. 10.1016/j.nano.2010.12.00310.1016/j.nano.2010.12.003 ↗
24. Glazer E. S. · Cancer · 2010 · 116 · 328510.1002/cncr.25135 ↗
25. Curley S. A. · J. Exp. Ther. Oncol. · 2008 · 7 · 313
26. Bhirde A. A. · ACS Nano · 2009 · 3 · 30710.1021/nn800551s ↗
27. Price B. K. · Chem. Mater. · 2009 · 21 · 391710.1021/cm9021613 ↗
28. Stephenson J. J. · Chem. Mater. · 2007 · 19 · 349110.1021/cm070076v ↗
29. Chen Z. Y. · J. Am. Chem. Soc. · 2006 · 128 · 1056810.1021/ja063283p ↗
30. Zhou G. · Oncogene · 2008 · 27 · 352710.1038/sj.onc.1211015 ↗