B.ELECTROFORESIS DE SEPARACIÓN DE ENANTIÓMEROS DE TALIDOMIDA

The authors thank Dr. David M. Goldenberg (Immunomedics, Inc., Morris Plains, NJ, USA) for providing the hKC4 antibody. The research project was funded by the Radboud University Nijmegen Medical Centre.

3

REFERENCES

1. Wang AZ, Langer RS, Farokhzad OC (2012) Nanoparticle Delivery of Cancer Drugs. Annu Rev Med 63: 185-198. 2. Byrne JD, Betancourt T, Brannon-Peppas L (2008) Active targeting schemes for nanoparticle systems in cancer

therapeutics. Adv Drug Deliv Rev 60: 1615-1626.

3. Zhang JA, Pawelchak J (2000) Effect of pH, ionic strength and oxygen burden on the chemical stability of EPC/ cholesterol liposomes under accelerated conditions. Part 1: Lipid hydrolysis. Eur J Pharm Biopharm 50: 357-364. 4. Ahmed F, Discher DE (2004) Self-porating polymersomes of PEG-PLA and PEG-PCL: hydrolysis-triggered

controlled release vesicles. J Control Release 96: 37-53.

5. Alexis F, Pridgen EM, Langer R, Farokhzad OC (2010) Nanoparticle technologies for cancer therapy. Handb Exp Pharmacol 55-86.

6. van Bracht E, Raave R, Verdurmen WP, Wismans RG, Geutjes PJ, et al. (2012) Lyophilisomes as a new generation of drug delivery capsules. Int J Pharm 439: 127-135.

7. Daamen WF, Geutjes PJ, Nillesen STM, Van Moerkerk HTB, Wismans R, et al. (2007) Lyophilisomes: A new type of (bio)capsules. Adv Mater 19: 673-677.

8. Kratz F (2008) Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. J Control Release 132: 171-183.

9. Elsadek B, Kratz F (2012) Impact of albumin on drug delivery - New applications on the horizon. J Control Release 157: 4-28.

10. Dinauer N, Balthasar S, Weber C, Kreuter J, Langer K, et al. (2005) Selective targeting of antibody-conjugated nanoparticles to leukemic cells and primary T-lymphocytes. Biomaterials 26: 5898-5906.

11. Steinhauser I, Spankuch B, Strebhardt K, Langer K (2006) Trastuzumab-modified nanoparticles: optimisation of preparation and uptake in cancer cells. Biomaterials 27: 4975-4983.

12. Feinstein SB, Cheirif J, Ten Cate FJ, Silverman PR, Heidenreich PA, et al. (1990) Safety and efficacy of a new transpulmonary ultrasound contrast agent: initial multicenter clinical results. J Am Coll Cardiol 16: 316-324. 13. Geny B, Mettauer B, Muan B, Bischoff P, Epailly E, et al. (1993) Safety and efficacy of a new transpulmonary echo

contrast agent in echocardiographic studies in patients. J Am Coll Cardiol 22: 1193-1198.

14. Ibrahim NK, Desai N, Legha S, Soon-Shiong P, Theriault RL, et al. (2002) Phase I and pharmacokinetic study of ABI-007, a Cremophor-free, protein-stabilized, nanoparticle formulation of paclitaxel. Clin Cancer Res 8: 1038-1044.

15. Ibrahim NK, Samuels B, Page R, Doval D, Patel KM, et al. (2005) Multicenter phase II trial of ABI-007, an albumin-bound paclitaxel, in women with metastatic breast cancer. J Clin Oncol 23: 6019-6026.

16. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K (2000) Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 65: 271-284.

17. Wagner S, Rothweiler F, Anhorn MG, Sauer D, Riemann I, et al. (2010) Enhanced drug targeting by attachment of an anti alphav integrin antibody to doxorubicin loaded human serum albumin nanoparticles. Biomaterials 31: 2388-2398.

18. Loomis K, Smith B, Feng Y, Garg H, Yavlovich A, et al. (2010) Specific targeting to B cells by lipid-based nanoparticles conjugated with a novel CD22-ScFv. Exp Mol Pathol 88: 238-249.

19. Van de BB, Devoogdt N, D’Hollander A, Gijs HL, Jans K, et al. (2011) Specific cell targeting with nanobody conjugated branched gold nanoparticles for photothermal therapy. ACS Nano 5: 4319-4328.

20. Levi E, Klimstra DS, Andea A, Basturk O, Adsay NV (2004) MUC1 and MUC2 in pancreatic neoplasia. J Clin Pathol 57: 456-462.

21. Singh PK, Hollingsworth MA (2006) Cell surface-associated mucins in signal transduction. Trends Cell Biol 16: 467-476.

22. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, et al. (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127: 2893-2917.

23. Yu C, Hu Y, Duan J, Yuan W, Wang C, et al. (2011) Novel aptamer-nanoparticle bioconjugates enhances delivery of anticancer drug to MUC1-positive cancer cells in vitro. PLoS One 6: e24077.

24. Gendler SJ (2001) MUC1, the renaissance molecule. J Mammary Gland Biol Neoplasia 6: 339-353.

25. Garza-Licudine E, Deo D, Yu S, Uz-Zaman A, Dunbar WB (2010) Portable nanoparticle quantization using a resizable nanopore instrument - the IZON qNano. Conf Proc IEEE Eng Med Biol Soc 2010: 5736-5739.

26. Kakade ML, Liener IE (1969) Determination of available lysine in proteins. Anal Biochem 27: 273-280. 27. Riener CK, Kada G, Gruber HJ (2002) Quick measurement of protein sulfhydryls with Ellman’s reagent and with

4,4’-dithiodipyridine. Anal Bioanal Chem 373: 266-276.

28. Simpson RJ (2008) Estimation of Free Thiols and Disulfide Bonds Using Ellman’s Reagent. CSH Protoc 2008: db. 29. Tario JD Jr., Gray BD, Wallace SS, Muirhead KA, Ohlsson-Wilhelm BM, et al. (2007) Novel lipophilic tracking dyes

for monitoring cell proliferation. Immunol Invest 36: 861-885.

30. Wallace PK, Tario JD Jr., Fisher JL, Wallace SS, Ernstoff MS, et al. (2008) Tracking antigen-driven responses by flow cytometry: monitoring proliferation by dye dilution. Cytometry A 73: 1019-1034.

31. Tanious FA, Veal JM, Buczak H, Ratmeyer LS, Wilson WD (1992) DAPI (4’,6-diamidino-2-phenylindole) binds differently to DNA and RNA: minor-groove binding at AT sites and intercalation at AU sites. Biochemistry 31: 3103-3112.

32. Lammers T, Kiessling F, Hennink WE, Storm G (2012) Drug targeting to tumors: Principles, pitfalls and (pre-) clinical progress. J Control Release 161: 175-187.

33. Cardoso MM, Peca IN, Roque AC (2012) Antibody-conjugated nanoparticles for therapeutic applications. Curr Med Chem 19: 3103-3127.

34. Cho K, Wang X, Nie S, Chen ZG, Shin DM (2008) Therapeutic nanoparticles for drug delivery in cancer. Clin Cancer Res 14: 1310-1316.

35. De Jong WH, Borm PJ (2008) Drug delivery and nanoparticles:applications and hazards. Int J Nanomedicine 3: 133-149.

36. Langer K, Balthasar S, Vogel V, Dinauer N, von Briesen H, et al. (2003) Optimization of the preparation process for human serum albumin (HSA) nanoparticles. Int J Pharm 257: 169-180.

37. Elzoghby AO, Samy WM, Elgindy NA (2012) Protein-based nanocarriers as promising drug and gene delivery systems. J Control Release 161: 38-49.

38. Hollingsworth MA, Swanson BJ (2004) Mucins in cancer: protection and control of the cell surface. Nat Rev Cancer 4: 45-60.

39. Chen Y, Clark S, Wong T, Chen Y, Chen Y, et al. (2007) Armed antibodies targeting the mucin repeats of the ovarian cancer antigen, MUC16, are highly efficacious in animal tumor models. Cancer Res 67: 4924-4932. 40. Wartlick H, Michaelis K, Balthasar S, Strebhardt K, Kreuter J, et al. (2004) Highly specific HER2-mediated cellular

uptake of antibody-modified nanoparticles in tumour cells. J Drug Target 12: 461-471. 41. Doherty GJ, McMahon HT (2009) Mechanisms of endocytosis. Annu Rev Biochem 78: 857-902. 42. Conner SD, Schmid SL (2003) Regulated portals of entry into the cell. Nature 422: 37-44.

43. Brandhonneur N, Chevanne F, Vie V, Frisch B, Primault R, et al. (2009) Specific and non-specific phagocytosis of ligand-grafted PLGA microspheres by macrophages. Eur J Pharm Sci 36: 474-485.

44. Hillaireau H, Couvreur P (2009) Nanocarriers’ entry into the cell: relevance to drug delivery. Cell Mol Life Sci 66: 2873-2896.