3 years ago

Novel reduction-sensitive micellar nanoparticles assembled from Rituximab–doxorubicin conjugates as smart and intuitive drug delivery systems for the treatment of non-Hodgkin's lymphoma

Novel reduction-sensitive micellar nanoparticles assembled from Rituximab–doxorubicin conjugates as smart and intuitive drug delivery systems for the treatment of non-Hodgkin's lymphoma
Dianwen Song, Ling Shu, Haiyan Chen, Lei Zhou, Min Mao, Tong Meng, Huabin Yin
In this study, a novel reduction-sensitive drug delivery system, the rituximab–doxorubicin (RTX-DOX) micellar nanoparticle (RDMN), was specially designed for targeted delivery and release of DOX in non-Hodgkin's lymphoma (NHL) cells. The RDMN was fabricated by self-assembling of amphiphilic RTX-DOX conjugates (RDCs), which were synthesized by conjugating the hydrophilic Fab fragments of RTX (an anti-CD20 monoclonal antibody) and hydrophobic DOXs by a reduction-responsive linker, 3-(2-Pyridyldithio) propionyl hydrazide (PDPH). The RDMNs were characterized via dynamic light scattering and transmission electron microscopy, both showed the sizes of approximately 94.1 ± 14.5 nm with a uniform size distribution. Polyplex dissociation, which was indicated by accelerated DOX release rate and increased particle size, was observed in the presence of 2.5 mm 1,4-dithiothreitol due to the cleavage of disulfide bonds in PDPH linkers. In vitro transfection assays against human NHL cell line, JeKo-1, showed significantly increased uptake for RDMNs, as compared to RDCs and free RTX/DOX. Both in and ex vivo experiments demonstrated that RDMNs showed the highest therapeutic effect among all the experimental groups. These results suggested that this RDMN could be a potential, safe and efficient drug delivery vector, which deserves further investigation in the clinic. A novel reduction-sensitive drug delivery system, the Rituximab-Doxorubicin (RTX-DOX) micellar nanoparticle (RDMN) was fabricated by self-assembling of amphiphilic RTX-DOX conjugates (RDCs) for targeted delivery and release of DOX in Non-Hodgkin's Lymphoma (NHL) cells in this study. Both in and ex vivo experiments demonstrated that RDMNs showed the highest therapeutic effect among all the experimental groups, which would be a potential, safe and efficient drug delivery vector.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/cbdd.13010

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