Following the FDA approval of anti-CD20 mAb Rituximab for CD20+ N

Following the FDA approval of anti-CD20 mAb Rituximab for CD20+ NHL treatment, monoclonal antibody (mAb)-based targeting therapy has revolutionized the treatment of malignancies for the specific antitumor activity and low cytotoxicity against normal tissues [22, 23]. In the last decade, more and more studies have confirmed that the combination of mAb-based learn more 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]. In this study, we have developed an adriamycin (ADR)-loaded Selleck MS-275 liposome using the diacetylenic

phosphatidylcholine 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC, hereafter referred to as PC), which can form intermolecular cross-linking through the diacetylenic group to produce a conjugated polymer within the hydrocarbon region of the bilayer by ultra-violet (UV) irradiation (Additional file 1: Figure S1) [26, 27]. For the sake of active targeting, the Fab fragments of rituximab were conjugated onto the liposomal surface. Our experimental results demonstrate that this well-modified www.selleckchem.com/products/jsh-23.html liposome, which owns good serum stability and prolonged circulation time, can accumulate in

the tumor tissues and malignant cells with high specificity and sufficient amount, which can bring out exceptional excellent and durable therapeutic efficacy against CD20-positive lymphomas. Methods Cell lines and materials Two human B cell lymphoma cell lines, Raji and Daudi, were obtained from the American Type Culture Collection (ATCC). Cells were propagated and maintained in RPMI 1640 supplemented with 10% (v/v) fetal bovine serum (FBS, GIBCO, Invitrogen, Carlsbad, CA, USA) in a controlled atmosphere GNAT2 incubator at 37°C with 5% CO2. The DC8,9PC and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethylene

glycol)-2000] (Mal-PEG) were purchased from Avanti Polar Lipids (Williamsport, PA, USA). The anti-CD20 antibodies rituximab was purchased from Roche (Basel, Switzerland). Fabrication of Fab fragment-conjugated liposome (Figure 1) Figure 1 Fabrication of rituximab Fab fragment-decorated liposomes. Formation of drug-loaded liposomes Total lipids mixtures of 2 mg DC8,9PC and 0.25 mg Mal-PEG were dissolved in 500 μL mixed solvent of chloroform and methyl alcohol with the volume ratio at 1:1. Then, the solvent was evaporated under vortex and flashed with nitrogen to obtain the lipid film, followed by washing-out with 2 mL of ADR (doxorubicin HCl, Melonepharma CO. LTD., Dalian, China) solution (0.5 mg/mL in PBS) to obtain ADR-loaded multilamellar vesicles [26]. The collected liposome solution was dialyzed against PBS using a membrane (molecular weight cutoff 3 kDa) at 4°C for 12 h to remove uncombined ADR resulting in the ADR-loaded liposome stocking solutions. Thiolation of mAbs The Fab fragment of rituximab was prepared as reported previously [25].

Comments are closed.