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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

Properties of CD20 targeting liposomes. (A) Size distribution of liposomes before or after UV irradiation. (B) The TEM morphology of the liposomes before or after UV irradiation, scale bar 0.5 μm. (C) The drug release profile of ADR-loaded liposomes before or after UV irradiation. (D) The cytotoxicity profile of the empty liposomes PC-BSA and PC-Fab incubated with CD20 overexpressed Raji cells.
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Figure 2: Properties of CD20 targeting liposomes. (A) Size distribution of liposomes before or after UV irradiation. (B) The TEM morphology of the liposomes before or after UV irradiation, scale bar 0.5 μm. (C) The drug release profile of ADR-loaded liposomes before or after UV irradiation. (D) The cytotoxicity profile of the empty liposomes PC-BSA and PC-Fab incubated with CD20 overexpressed Raji cells.

Mentions: It has been firmly established that size distribution of a liposome strongly affect its in vitro and in vivo performances [17,25]. Therefore, we firstly assessed the size distribution of our liposome after the successful fabrication. Figure 2A shows the size distribution of irrad and non-irrad liposomes. It was illustrated that an 11% decrease in mean size was occurred after UV irradiation (from approximately 321 nm before irradiation to 285 nm after irradiation). This interesting physical change was validated by morphology analysis using a TEM, of which the results suggested that both the irrad and non-irrad liposome showed a regular spherical morphology with different diameters (Figure 2B).


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)

Properties of CD20 targeting liposomes. (A) Size distribution of liposomes before or after UV irradiation. (B) The TEM morphology of the liposomes before or after UV irradiation, scale bar 0.5 μm. (C) The drug release profile of ADR-loaded liposomes before or after UV irradiation. (D) The cytotoxicity profile of the empty liposomes PC-BSA and PC-Fab incubated with CD20 overexpressed Raji cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Properties of CD20 targeting liposomes. (A) Size distribution of liposomes before or after UV irradiation. (B) The TEM morphology of the liposomes before or after UV irradiation, scale bar 0.5 μm. (C) The drug release profile of ADR-loaded liposomes before or after UV irradiation. (D) The cytotoxicity profile of the empty liposomes PC-BSA and PC-Fab incubated with CD20 overexpressed Raji cells.
Mentions: It has been firmly established that size distribution of a liposome strongly affect its in vitro and in vivo performances [17,25]. Therefore, we firstly assessed the size distribution of our liposome after the successful fabrication. Figure 2A shows the size distribution of irrad and non-irrad liposomes. It was illustrated that an 11% decrease in mean size was occurred after UV irradiation (from approximately 321 nm before irradiation to 285 nm after irradiation). This interesting physical change was validated by morphology analysis using a TEM, of which the results suggested that both the irrad and non-irrad liposome showed a regular spherical morphology with different diameters (Figure 2B).

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