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Biomedical subjects

Xiaogang Pan

Publications and source records attributed to Xiaogang Pan.

4 recordsLinked to original sources
PubMed2006

Construction of anti-EGFR immunoliposomes via folate-folate binding protein affinity.

A novel method for synthesis of anti-EGFR immunoliposomes using folate-folate binding protein (FBP) affinity is described. An anti-EGFR antibody (cetuximab or C225) was covalently linked to FBP via a thioether bond. Liposomes incorporating a lipophilic folate derivative (folate-PEG-cholesterol) were prepared by polycarbonate membrane extrusion. Anti-EGFR immunoliposomes were then obtained by combining FBP-C225 and folate-liposomes and evaluated for uptake and cytotoxicity in EGFR-overexpressing U87 human glioblastoma cells. Anti-EGFR immunoliposomes constructed via folate-FBP affinity exhibited excellent stability under physiological pH, and quickly released the bound FBP-C225 upon low pH (pH 3.5) treatment. Flow cytometry and fluorescence microscopy showed similar receptor-specific binding and internalization for both folate-FBP affinity-coupled and covalently coupled C225-immunoliposomes, but not for the non-targeted IgG-immunoliposomes. C225-immunoliposomes loaded with anticancer drug doxorubicin were more cytotoxic than non-targeted immunoliposomes in EGFR-overexpressing U87 glioma cells. Folate-FBP affinity is a potential method for construction of immunoliposomes and may have applications in synthesis of targeted drug carriers in general.

Antibodies, Monoclonal↗
PubMed2004

Tumour-selective drug delivery via folate receptor-targeted liposomes.

Tumour cell-targeted liposomal delivery has the potential to enhance the therapeutic efficacy and reduce the toxicity of anticancer agents. Folate receptor (FR) expression is frequently amplified among human malignancies. FR is, therefore, potentially useful as a tumour marker for targeted drug delivery. FR-mediated liposomal delivery has been shown to enhance the antitumour efficacy of doxorubicin both in vitro and in vivo, and to overcome P-glycoprotein-mediated multi-drug resistance. In addition, FR-targeted liposomes have shown utility as effective delivery vehicles of genes and antisense oligodeoxyribonucleotides to FR(+) tumour cells. Both solid tumours and leukaemias can potentially benefit from FR-targeted drug delivery. Multiple mechanisms might contribute to greater therapeutic efficacy for FR-targeted liposomes, such as FR-dependent cytotoxicity and antiangiogenic activity. Further investigation of this promising drug delivery strategy is clearly warranted.

Antineoplastic Agents↗
PubMedDate not supplied

Synthesis of cetuximab-immunoliposomes via a cholesterol-based membrane anchor for targeting of EGFR.

The objective of the present study was to construct epidermal growth factor receptor (EGFR) targeting cetuximab-immunoliposomes (ILs) for targeted delivery of boron compounds to EGFR(+) glioma cells for neutron capture therapy. The ILs were synthesized by using a novel cholesterol-based membrane anchor, maleimido-PEG-cholesterol (Mal-PEG-Chol), to incorporate cetuximab into liposomes by either surface conjugation or a post-insertion method. For post-insertion, the transfer efficiency of MAb conjugates from micelles to liposome was examined at varying temperatures, mPEG2000-DSPE ratios, and micelle-to-liposome lipid ratios. Following this, the cetuximab-ILs were evaluated for targeted delivery of the encapsulated boron anion, dodecahydro-closo-dodecaborate (2-) (B12H122-), to human EGFR gene transfected F98EGFR glioma cells as potential delivery agents for boron neutron capture therapy (BNCT). In addition, cellular uptake of cetuximab-ILs, encapsulating a fluorescence dye, was analyzed by confocal fluorescence microscopy and flow cytometry, and boron content was quantified by ICP-MS. Much greater ( approximately 8-fold) cellular uptake of boron was obtained using cetuximab-ILs in EGFR(+) F98EGFR compared with nontargeted human IgG-ILs. On the basis of these observations, we have concluded that cholesterol can serve as an effective anchor for MAb in liposomes, and cetuximab-ILs are potentially useful delivery vehicles for BNCT of gliomas.

Antibodies, Monoclonal↗