Abstract
Unlike most malignancies, chemotherapy but not surgery plays the most important role in treating non-Hodgkin lymphoma (NHL). Currently, liposomes have been widely used to encapsulate chemotherapeutic drugs in treating solid tumors. However, higher in vivo stability owns a much more important position for excellent antitumor efficacy in treating hematological malignancies. In this study, we finely fabricated a rituximab Fab fragment-decorated liposome based on 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC), which can form intermolecular cross-linking through the diacetylenic group by ultra-violet (UV) irradiation. Our experimental results demonstrated that after the UV irradiation, the liposomes exhibit better serum stability and slower drug release with a decreased mean diameter of approximately 285 nm. The cellular uptake of adriamycin (ADR) by this Fab-navigated liposome was about four times of free drugs. Cytotoxicity assays against CD20+ lymphoma cells showed that the half maximal (50%) inhibitory concentration (IC50) of ADR-loaded immunoliposome was only one fourth of free ADR at the same condition. In vivo studies were evaluated in lymphoma-bearing SCID mice. With the high serum stability, finely regulated structure, active targeting strategy via antigen-antibody reaction and passive targeting strategy via enhanced permeability and retention (EPR) effect, our liposome exhibits durable and potent antitumor activities both in the disseminated and localized human NHL xeno-transplant models.
Highlights
Non-Hodgkin lymphoma (NHL) is a type of blood cancer, which presents as a solid tumor of lymphoid cells in lymph nodes and/or extranodal lymphatic organs such as spleen and bone marrow, and as free lymphoma cells in circulating blood [1,2,3]
Encapsulation of bioactive reagents in nanocarriers can result in significant accumulation and retention in solid tumor tissues relative to administration of drug in conventional formulations through the enhanced permeability and retention (EPR) effect, which was firstly described by Maeda and colleagues [13,14,15,16,17]
This interesting physical change was validated by morphology analysis using a TEM, of which the results suggested that both the irrad and non-irrad
Summary
Non-Hodgkin lymphoma (NHL) is a type of blood cancer, which presents as a solid tumor of lymphoid cells in lymph nodes and/or extranodal lymphatic organs such as spleen and bone marrow, and as free lymphoma cells in circulating blood [1,2,3]. Nanocarriers, including liposomes, polymeric nanoparticles, micelles, nanogels etc., with an appropriate diameter of tens to hundreds of nanometers, have received widespread attention for the specific delivery of bioactive reagents in the diagnosis and treatment of cancer [7,9,10,11,12]. What's more, the drug loading nanocarriers owns high serum stability, which can contribute to long-time circulation in the blood vessels, resulting in long-lasting antitumor activities, especially for the killing of free malignant cells in circulating blood [12,17,18]. More and more studies have confirmed that the combination of mAb-based active targeting and nanoparticle-based passive targeting can improve drug concentration in tumor tissues and tumor cells in a shorter time with greater accuracy [7,24,25]
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