Targeted treatment of CD22-positive non-Hodgkin’s lymphoma with sialic acid–modified chitosan-PLGA hybrid nanoparticles
- 57 Downloads
B cell–derived non-Hodgkin’s lymphoma is a lymphatic system tumor that is a serious threat to human health. It is mainly treated by chemotherapy drugs. However, the lack of targeted performance of drug has always been one of the important reasons for limiting application in clinical. In this study, negatively charged sialic acid (SA)–modified PLGA nanoparticles (NPs) were prepared under the guidance of cationic chitosan, and the anti-tumor drug doxorubicin (DOX) was loaded to obtain DOX/SC-PLGA NP (195.9 ± 2.3 nm). In the drug release experiment, it was revealed that the drug-loaded nanoparticles can be destroyed under acidic conditions to rapidly release the drug due to the charge reversal. In in vitro flow cytometry experiments, SA-modified NP not only can promote more uptake by CD22-positive Raji cells but also can promote upregulation of Bax and downregulation of Bcl-2 expression, thereby promoting tumor cell apoptosis. The MTT assay also confirmed that DOX/SC-PLGA NP can effectively reduce the cell viability of Raji cells and JeKo-1 cells. In the NHL model of Raji cell transplantation tumor mice, DOX/SC-PLGA NP not only shows superior tumor targeting ability but also reduces the enrichment of DOX in the lungs and kidneys, and reduces the myelosuppressive effect of DOX. In the observation of efficacy, it was found that DOX/SC-PLGA NP significantly reduced the tumor volume of NHL. The linear relationship between tumor drug concentration and tumor volume also shows that SC-PLGA NP can better aggregate and exert therapeutic effects in NHL. The above results indicate that SA, as a ligand for CD22, can be used as a good nanomedicine targeting unit for the treatment of NHL models with high CD22 expression.
KeywordsSialic acid CD22 Nanocarrier Non-Hodgkin’s lymphoma Targeted therapy Nanomedicine
Thanks to the Analysis Center of Kunming University of Science and Technology for assistance with TEM.
Compliance with ethical standards
All animal experiments comply with the ARRIVE guidelines and were carried out in accordance with the UK Animals (Scientific Procedures) Act, 1986 and associated guidelines, EU Directive 2010/63/EU for animal experiments.
Conflict of interest
The authors declare that they have no competing interests.
- Bartlett NL, Petroni GR, Parker BA, Wagner ND, Gockerman JP, Omura GA, Canellos GP, Cooper MR, Johnson JL, Peterson BA (2001) Dose-escalated cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (CHOPE) chemotherapy for patients with diffuse lymphoma: cancer and leukemia group B studies 8852 and 8854. Cancer 92:207–217CrossRefGoogle Scholar
- Bierman PJ, Sweetenham JW, Loberiza FR Jr, Taghipour G, Lazarus HM, Rizzo JD, Schmitz N, van Besien K, Vose JM, Horowitz M, Goldstone A, Lymphoma Working Committee of the International Bone Marrow Transplant Registry and the European Group for Blood and Marrow Transplantation (2003) Syngeneic hematopoietic stem-cell transplantation for non-Hodgkin’s lymphoma: a comparison with allogeneic and autologous transplantation--the Lymphoma Working Committee of the International Bone Marrow Transplant Registry and the European Group for Blood and Marrow Transplantation. J Clin Oncol 21:3744–3753. https://doi.org/10.1200/JCO.2003.08.054 CrossRefGoogle Scholar
- Carella AM, Cavaliere M, Lerma E, Ferrara R, Tedeschi L, Romanelli A, Vinci M, Pinotti G, Lambelet P, Loni C, Verdiani S, de Stefano F, Valbonesi M, Corsetti MT (2000) Autografting followed by nonmyeloablative immunosuppressive chemotherapy and allogeneic peripheral-blood hematopoietic stem-cell transplantation as treatment of resistant Hodgkin’s disease and non-Hodgkin’s lymphoma. J Clin Oncol 18:3918–3924. https://doi.org/10.1200/JCO.2000.18.23.3918 CrossRefGoogle Scholar
- Clarke CA, Morton LM, Lynch C, Pfeiffer RM, Hall EC, Gibson TM, Weisenburger DD, Martínez-Maza O, Hussain SK, Yang J, Chang ET, Engels EA (2013) Risk of lymphoma subtypes after solid organ transplantation in the United States. Br J Cancer 109:280–288. https://doi.org/10.1038/bjc.2013.294 CrossRefGoogle Scholar
- Gale RP (1985) Antineoplastic chemotherapy myelosuppression: mechanisms and new approaches. Exp Hematol 13(Suppl 16):3–7Google Scholar
- Maloney DG, Grillo-López AJ, White CA, Bodkin D, Schilder RJ, Neidhart JA, Janakiraman N, Foon KA, Liles TM, Dallaire BK, Wey K, Royston I, Davis T, Levy R (1997) IDEC-C2B8 (rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin’s lymphoma. Blood 90:2188–2195Google Scholar
- Miller TP, Dahlberg S, Cassady JR, Adelstein DJ, Spier CM, Grogan TM, LeBlanc M, Carlin S, Chase E, Fisher RI (1998) Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin’s lymphoma. N Engl J Med 339:21–26. https://doi.org/10.1056/NEJM199807023390104 CrossRefGoogle Scholar
- Morell AG, Gregoriadis G, Scheinberg IH, Hickman J, Ashwell G (1971) The role of sialic acid in determining the survival of glycoproteins in the circulation. J Biol Chem 246:1461–1467Google Scholar
- Perry AM, Diebold J, Nathwani BN, MacLennan KA, Muller-Hermelink HK, Bast M, Boilesen E, Armitage JO, Weisenburger DD (2016) Non-Hodgkin lymphoma in the developing world: review of 4539 cases from the International Non-Hodgkin Lymphoma Classification Project. Haematologica 101:1244–1250. https://doi.org/10.3324/haematol.2016.148809 CrossRefGoogle Scholar