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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

Liposomal in vitro serum stability assessment. Up panel: size distribution of the liposome dilution in RPMI 1640 containing 50% (m/v) BSA. Down panel: size distribution of the above dilution after the incubation at 37°C for 24 h. Red, liposomes before UV irradiation; black, liposome after UV irradiation.
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Figure 3: Liposomal in vitro serum stability assessment. Up panel: size distribution of the liposome dilution in RPMI 1640 containing 50% (m/v) BSA. Down panel: size distribution of the above dilution after the incubation at 37°C for 24 h. Red, liposomes before UV irradiation; black, liposome after UV irradiation.

Mentions: For future clinical applications, the in vivo stability of liposome is another important factor which should be considered. Therefore, we used the RPMI 1640 containing 50% BSA as an in vitro model of serum to check the serum stability profile of our liposomes, in which the existence of BSA was employed to mimic a variety of serum proteins in the complicated environment within the blood vessels. Figure 3 shows the size distribution of liposome solutions before (red) and after (black) UV irradiation. The first individual peak in each histogram represents the size distribution of BSA, and the second represents that of liposomes. The results indicated that after the dilution of liposomes in serum model, the size distribution of each sample was similar as separately measured (Figure 3A), while after a 24-h incubation, the well-separated peaks for BSA and liposomes still appeared in the mixture, which is an indication of good serological stability. However, the non-irrad liposomes in the mixture showed a much broader size distribution (Figure 3B). The results revealed that after the UV irradiation, our liposomes showed better stability in the serum model than non-irrad ones.


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)

Liposomal in vitro serum stability assessment. Up panel: size distribution of the liposome dilution in RPMI 1640 containing 50% (m/v) BSA. Down panel: size distribution of the above dilution after the incubation at 37°C for 24 h. Red, liposomes before UV irradiation; black, liposome after UV irradiation.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Liposomal in vitro serum stability assessment. Up panel: size distribution of the liposome dilution in RPMI 1640 containing 50% (m/v) BSA. Down panel: size distribution of the above dilution after the incubation at 37°C for 24 h. Red, liposomes before UV irradiation; black, liposome after UV irradiation.
Mentions: For future clinical applications, the in vivo stability of liposome is another important factor which should be considered. Therefore, we used the RPMI 1640 containing 50% BSA as an in vitro model of serum to check the serum stability profile of our liposomes, in which the existence of BSA was employed to mimic a variety of serum proteins in the complicated environment within the blood vessels. Figure 3 shows the size distribution of liposome solutions before (red) and after (black) UV irradiation. The first individual peak in each histogram represents the size distribution of BSA, and the second represents that of liposomes. The results indicated that after the dilution of liposomes in serum model, the size distribution of each sample was similar as separately measured (Figure 3A), while after a 24-h incubation, the well-separated peaks for BSA and liposomes still appeared in the mixture, which is an indication of good serological stability. However, the non-irrad liposomes in the mixture showed a much broader size distribution (Figure 3B). The results revealed that after the UV irradiation, our liposomes showed better stability in the serum model than non-irrad ones.

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