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

Cong Wu1, Huafei Li12*, He Zhao3, Weiwei Zhang1, Yan Chen1, Zhanyi Yue1, Qiong Lu1, Yuxiang Wan1, Xiaoyu Tian1 and Anmei Deng1*

Author Affiliations

1 Department of Laboratory Diagnosis, Changhai Hospital affiliated to the Second Military Medical University, 168 Changhai Road, Shanghai 200433, China

2 International Joint Cancer Institute, the Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China

3 Institute of Pediatric Research, Children's Hospital affiliated to Soochow University, 303 Jingde Road, Suzhou 215000, China

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Nanoscale Research Letters 2014, 9:447  doi:10.1186/1556-276X-9-447

Published: 28 August 2014

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.

Keywords:
Non-Hodgkin lymphoma; Rituximab; Chemotherapy; Liposomes; Serum stability; Ultra-violet irradiation polymerizing