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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.

Wu C, Li H, Zhao H, Zhang W, Chen Y, Yue Z, Lu Q, Wan Y, Tian X, Deng A - Nanoscale Res Lett (2014)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

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

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.

No MeSH data available.


Related in: MedlinePlus

Fabrication of rituximab Fab fragment-decorated liposomes.
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Figure 1: Fabrication of rituximab Fab fragment-decorated liposomes.

Mentions: 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 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).


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

Wu C, Li H, Zhao H, Zhang W, Chen Y, Yue Z, Lu Q, Wan Y, Tian X, Deng A - Nanoscale Res Lett (2014)

Fabrication of rituximab Fab fragment-decorated liposomes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4151082&req=5

Figure 1: Fabrication of rituximab Fab fragment-decorated liposomes.
Mentions: 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 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).

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

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

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.

No MeSH data available.


Related in: MedlinePlus