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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
Author(s) -
Yin Huabin,
Meng Tong,
Shu Ling,
Mao Min,
Zhou Lei,
Chen Haiyan,
Song Dianwen
Publication year - 2017
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13010
Subject(s) - chemistry , doxorubicin , conjugate , drug delivery , dynamic light scattering , dithiothreitol , linker , biophysics , rituximab , combinatorial chemistry , pharmacology , biochemistry , nanoparticle , lymphoma , nanotechnology , chemotherapy , immunology , materials science , organic chemistry , medicine , mathematical analysis , surgery , mathematics , computer science , biology , enzyme , operating system
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 ( RDC s), which were synthesized by conjugating the hydrophilic Fab fragments of RTX (an anti‐ CD 20 monoclonal antibody) and hydrophobic DOX s by a reduction‐responsive linker, 3‐(2‐Pyridyldithio) propionyl hydrazide ( PDPH ). The RDMN s 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 m m 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 RDMN s, as compared to RDC s and free RTX / DOX . Both in and ex vivo experiments demonstrated that RDMN s 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.