Tumor-Specific Anti-Nucleosome Antibody Improves Therapeutic Efficacy of Doxorubicin-Loaded Long-Circulating Liposomes against Primary and Metastatic Tumor in Mice
Abstract:The efficacy of drug delivery systems can be significantly enhanced by making them target-specific via the attachment of various ligands to their surface. We attempted to enhance tumor accumulation and therapeutic effect of doxorubicin-loaded long-circulating liposomes (Doxil ® , ALZA Corp.) by coupling to their surface the anti-cancer monoclonal antibody 2C5 (mAb 2C5) with nuclesome (NS)-restricted activity, that can recognize the surface of various tumor but not normal cells via the surfacebound nucleosomes … Show more
“…The loading efficiency of DXR in liposomes was determined by measuring the fluorescence of DXR (Ex=450 nm, Em=590 nm) of prepared liposomes following treatment with MeOH to disrupt the liposome structure. Doxil (doxorubicin encapsulated in small sized liposomes) were prepared as described previously [15].…”
Anti-angiogenic therapy is a potential chemotherapeutic strategy for the treatment of drug resistant cancers. However, a method for delivering such drugs to tumor endothelial cells remains to be a major impediment to the success of anti-angiogenesis therapy. We designed
“…The loading efficiency of DXR in liposomes was determined by measuring the fluorescence of DXR (Ex=450 nm, Em=590 nm) of prepared liposomes following treatment with MeOH to disrupt the liposome structure. Doxil (doxorubicin encapsulated in small sized liposomes) were prepared as described previously [15].…”
Anti-angiogenic therapy is a potential chemotherapeutic strategy for the treatment of drug resistant cancers. However, a method for delivering such drugs to tumor endothelial cells remains to be a major impediment to the success of anti-angiogenesis therapy. We designed
“…The G3 nanoglobule, (L-Lysine) 32 -(L-lysine) 16 -(L-lysine) 8 -OAS, was synthesized as described earlier (10). G3 (89.0 mg, 5.8 mmol), HOBT (13.4 mg, 0.99 mmol) and HBTU (37.6 mg, 0.99 mmol) were dissolved in DMF (1 ml) and 3-mercaptopropanoic acid (MPA) (3.23 ml, 37 mmol) was separately diluted in DMF (0.2 ml).…”
Section: Preparation Of G3-[3-mercaptopropanamide] (G3-[sh])mentioning
confidence: 99%
“…However, they suffer various limitations for drug delivery. Liposomes have a relatively large payload, but formulation of liposomal delivery systems is relatively complicated and the surface of liposomes needs to be modified with biocompatible polymers to minimize non-specific tissue uptake [8]. Synthetic biocompatible macromolecules can accommodate different therapeutic agents for codelivery, but most of the synthetic macromolecules are mixtures of polymers of different sizes and do not have uniform and constant morphology before and after chemical modifications, which may complicate their pharmacokinetic properties during in vivo applications [9].…”
“…The 2C5 Ab specifically recognises extracellular and tumour-cell bound nucleosomes that arise from apoptotic tumour cells in-vivo [75]. Even when used at subtherapeutic quantities, 2C5 is an effective tumour targeting moiety for PLD, also showing efficacy against primary and metastatic lung tumours in mice [75].…”
Section: Delivery Of Cytotoxic Agentsmentioning
confidence: 99%
“…The 2C5 Ab specifically recognises extracellular and tumour-cell bound nucleosomes that arise from apoptotic tumour cells in-vivo [75]. Even when used at subtherapeutic quantities, 2C5 is an effective tumour targeting moiety for PLD, also showing efficacy against primary and metastatic lung tumours in mice [75]. Central nervous system (CNS) tumours present a unique challenge to treatment due to the presence of the blood brain barrier (BBB); a unique physiological barrier which functions to protect the brain but also limits drug delivery to the CNS [83].…”
Nanoparticles are diverse and versatile with physical properties that can be employed for use in cancer medicine. Targeting nanoparticles using antibodies and antibody fragments could overcome some of the limitations seen with current targeted therapies. This review will discuss the role of antibody-targeted nanoparticles in the treatment of cancer: as delivery vehicles, targeted theranostic agents and in the evolving field of cancer hyperthermia.
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