Combination of daratumumab and doxorubicin loaded polycaprolactone nanoparticles in the treatment of diffuse large B-cell lymphoma
Combination of daratumumab and doxorubicin loaded polycaprolactone nanoparticles in the treatment of diffuse large B-cell lymphoma
Aim: The purpose of this study is to evaluate the activity of daratumumab in combination with polycaprolactone (PCL) nanoparticles (NPs) for decreasing toxicity and enhancing the anticancer efficiency of doxorubicin (Dox) for diffuse large B-cell lymphoma (DLBCL). Material and Methods: Polycaprolactone nanoparticles were developed using double emulsion technique. For characterization of blank and doxorubicin loaded PCL nanoparticles; particle size, polydispersity index and surface charge were determined. Cell culture study was realized to conclude the cytotoxicity of Dox-loaded PCL NPs alone or combination with Daratumumab. Results: Blank and Dox-loaded PCL nanoparticles remained within 235 nm and 250 nm, respectively. Zeta potential values were -3.9 and -13.3 mV for blank and Dox-loaded PCL nanoparticles, respectively. In cell culture study, whole formulations showed a timedependent model; the cytotoxicity enhanced with the increase of incubation time. Blank nanoparticles have no toxicity; cell viability was above 85%. Dox-loaded nanoparticles showed more toxicity to A20 cells than Dox solution. Dox-loaded NPs in combination Daratumumab exhibited higher cell toxicity than Dox-loaded NPs and mAb solution, respectively (P < 0.05). Conclusion: Dox-loaded PCL nanoparticles in combination with antibody-targeted chemotherapy could be a considered as promising synergistic strategy for controlling tumor growth by increasing the antitumor efficacy while minimizing toxicity.
___
- 1. Knapp CM, Whitehead KA. In pursuit of a moving target: nanotherapeutics for the treatment of non-Hodgkin B-cell lymphoma. Expert opinion on drug delivery. 2014;11(12):1923-37.
- 2. Li H, Guo K, Wu C, Shu L, Guo S, Hou J, et al. Controlled and Targeted Drug Delivery by a UV-responsive Liposome for Overcoming Chemo-resistance in Non-Hodgkin Lymphoma. Chem Biol Drug Des. 2015;86(4):783-94.
- 3. Sehn LH, Donaldson J, Chhanabhai M, Fitzgerald C, Gill K, Klasa R, et al. Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2005;23(22):5027-33.
- 4. Allen TM. Ligand-targeted therapeutics in anticancer therapy. Nature reviews Cancer. 2002;2(10):750-63.
- 5. Barenholz Y. Doxil(R)–the first FDA-approved nano-drug: lessons learned. Journal of controlled release : official journal of the Controlled Release Society. 2012;160(2):117-34.
- 6. Gabizon A, Catane R, Uziely B, Kaufman B, Safra T, Cohen R, et al. Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethyleneglycol coated liposomes. Cancer research. 1994;54(4):987-92.
- 7. Chen WC, Completo GC, Sigal DS, Crocker PR, Saven A, Paulson JC. In vivo targeting of B-cell lymphoma with glycan ligands of CD22. Blood. 2010;115(23):4778-86.
- 8. Park J, Fong PM, Lu J, Russell KS, Booth CJ, Saltzman WM, et al. PEGylated PLGA nanoparticles for the improved delivery of doxorubicin. Nanomedicine : nanotechnology, biology, and medicine. 2009;5(4):410-8.
- 9. Kingsley JD, Dou H, Morehead J, Rabinow B, Gendelman HE, Destache CJ. Nanotechnology: a focus on nanoparticles as a drug delivery system. J Neuroimmune Pharmacol. 2006;1(3):340- 50.
- 10. Bei D, Meng J, Youan BB. Engineering nanomedicines for improved melanoma therapy: progress and promises. Nanomedicine (Lond). 2010;5(9):1385-99.
- 11. Nevala WK, Buhrow SA, Knauer DJ, Reid JM, Atanasova EA, Markovic SN. Antibody-Targeted Chemotherapy for the Treatment of Melanoma. Cancer research. 2016;76(13):3954-64.
- 12. McKeage K. Daratumumab: First Global Approval. Drugs. 2016;76(2):275-81.
- 13. Vidal-Crespo A, Matas-Cespedes A, Rodriguez V, Rossi C, Valero JG, Serrat N, et al. Daratumumab displays in vitro and in vivo anti-tumor activity in models of B-cell non- Hodgkin lymphoma and improves responses to standard chemoimmunotherapy regimens. Haematologica. 2020;105(4):1032-41.
- 14. Varan C, Bilensoy E. Cationic PEGylated polycaprolactone nanoparticles carrying post-operation docetaxel for glioma treatment. Beilstein J Nanotechnol. 2017;8:1446-56.
- 15. Erdogar N, Iskit AB, Eroglu H, Sargon MF, Mungan NA, Bilensoy E. Cationic core-shell nanoparticles for intravesical chemotherapy in tumor-induced rat model: Safety and efficacy. International journal of pharmaceutics. 2014;471(1-2):1-9.
- 16. Maeda H, Nakamura H, Fang J. The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Advanced drug delivery reviews. 2013;65(1):71-9.
- 17. Bertrand N, Wu J, Xu X, Kamaly N, Farokhzad OC. Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. Advanced drug delivery reviews. 2014;66:2-25.
- 18. Molavi O, Xiong X-B, Douglas D, Kneteman N, Nagata S, Pastan I, et al. Anti-CD30 antibody conjugated liposomal doxorubicin with significantly improved therapeutic efficacy against anaplastic large cell lymphoma. Biomaterials. 2013;34(34):8718- 25.
- 19. Lidicky O, Klener P, Machova D, Vockova P, Pokorna E, Helman K, et al. Overcoming resistance to rituximab in relapsed non-Hodgkin lymphomas by antibody-polymer drug conjugates actively targeted by anti-CD38 daratumumab. Journal of controlled release : official journal of the Controlled Release Society. 2020;328:160-70.
- 20. Martinez NY, Andrade PF, Duran N, Cavalitto S. Development of double emulsion nanoparticles for the encapsulation of bovine serum albumin. Colloids Surf B Biointerfaces. 2017;158:190-6.
- 21. Erdogar N, Iskit AB, Mungan NA, Bilensoy E. Prolonged retention and in vivo evaluation of cationic nanoparticles loaded with Mitomycin C designed for intravesical chemotherapy of bladder tumours. Journal of microencapsulation. 2012;29(6):576-82.
- 22. Zhong W, Zhang X, Zhao M, Wu J, Lin D. Advancements in nanotechnology for the diagnosis and treatment of multiple myeloma. Biomater Sci. 2020;8(17):4692-711.
- 23. Ghosh S, Lalani R, Patel V, Bardoliwala D, Maiti K, Banerjee S, et al. Combinatorial nanocarriers against drug resistance in hematological cancers: Opportunities and emerging strategies. Journal of controlled release : official journal of the Controlled Release Society. 2019;296:114-39.
- 24. Karaarslan N, Yilmaz I, Sirin DY. Toxicity of the acetylpara- aminophenol group of medicines to intact intervertebral disc tissue cells. Experimental and therapeutic medicine