Potentiating antilymphoma efficacy of chemotherapy using a liposome for integration of CD20 targeting, ultra-violet irradiation polymerizing, and controlled drug delivery

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.

WITHDRAWN: Effective suppression of Rituximab-resistant B-cell lymphoma by a comb-like anti-CD20 mAb nanocluster

“…Rituximab (Rtx), the first US FDA (Food and Drug Administration)-approved monoclonal antibody (mAb) for treating non-Hodgkin lymphoma (NHL), targets the CD20 antigen and leads to CD20 + B-cell depletion [1][2][3][4]. Currently, Rituximab is routinely incorporated into all phases of conventional treatment, including first-line therapy, maintenance and salvage therapy [5,6].…”

Type II anti-CD20 mAb-induced lysosome mediated cell death is mediated through a ceramide-dependent pathway

“…Although clinical applications have proven unprecedented success of Rituximab in treating a variety range of non-Hodgkin lymphomas (NHLs), only 48% of patients respond to the treatment, with a complete remission (CR) rate of less than 10% [2]. Moreover, tumor relapse is inevitable for most patients [3,4]. Previous studies demonstrated that the exhaustion and anergy of effector cells and complements are involved in the limitations of Rituximab based immunotherapy [5,6].…”

Targeted and controlled drug delivery using a temperature and ultra-violet responsive liposome with excellent breast cancer suppressing ability

“…2 However, this pharmacokinetic sweet spot can hardly be achieved due to the distinctly different transient states of drugs in adhesion, distribution, metabolism and excretion (ADME). [3][4][5] Moreover, cancer cells tend to develop drug resistance, especially multidrug resistance (MDR), during the prolonged course of chemotherapy, characterized by cancer progression or recurrence. [3][4][5] Moreover, cancer cells tend to develop drug resistance, especially multidrug resistance (MDR), during the prolonged course of chemotherapy, characterized by cancer progression or recurrence.…”

“…3,7 With the development of material science and nanotechnology, nanoparticles based drug delivery systems (DDS) offer new hopes for improving the efficiency of chemotherapy with the following potential advantages: rstly, nanoparticles with desired size (e.g., 100-200 nm in diameter) could escape from the reticuloendothelial system (RES) to realize a favorable in vivo stability in the circulating blood. 2,5,11 Finally, nanoparticles are not physically recognized as substrates by the ATP-binding cassette (ABC) efflux pumps, which are proved to be overexpressed on chemo-resistant cancer cells and can extrude toxins from cells, conferring MDR to a broad spectrum of cytotoxic agents. 9,10 Thirdly, nanoparticles decorated with various ligands, such as monoclonal antibodies (mAbs), can realize targeted delivery and thus enhance internalization of encapsulated agents into tumor cells via endocytosis.…”

“…12,13 Up to now, two representative nanomedicines, Doxil and Abraxane, have been approved by the U.S. Food and Drug Administration (FDA). 2,5,16,17 However, it seems that more stable of a DDS means more difficult to release its content at the vicinity of tumors, and vice versa. have been extensively investigated recently for their effectiveness in diagnosing and treating malignancies.…”