Role of tumor vascular architecture in drug delivery

Nanoscale Small Interfering RNA Delivery Systems For Personalized Cancer Therapy

“…The targeting ligands enable nanoparticles to bind to cell surface receptors and enter cells by receptor-mediated endocytosis [19]. An excellent potential target for the biotargeting moieties of siRNA nanoparticles is the CD19 receptor of B-lineage leukemia/lymphoma cells [59][60][61].…”

“…CD19 is a 95-kDa B-lineage restricted receptor molecule that functions as a key regulator of transmembrane signals in both B-cells and B-cell precursors [59][60][61]. CD19 antigen is acquired at a very early stage of B-cell ontogeny, prior to rearrangement of immunoglobulin genes and expression of other B-precursor antigens such as CD10 and CD22 [59][60][61].…”

“…CD19 antigen is acquired at a very early stage of B-cell ontogeny, prior to rearrangement of immunoglobulin genes and expression of other B-precursor antigens such as CD10 and CD22 [59][60][61]. CD19 antigen is abundantly expressed on the malignant cells from B-lineage leukemia and lymphoma patients, but it is absent on the parenchymal cells of life-maintaining non-hematopoietic organs, circulating blood myeloid and erythroid cells, T-cells as well as bone marrow stem cells, [59][60][61]. In B-lineage ALL, CD19 antigen is expressed on candidate leukemic stem cell populations with in vivo clonogenic, leukemia initiating and propagating properties in xenograft models using immunocompromised mice.…”

“…In B-lineage ALL, CD19 antigen is expressed on candidate leukemic stem cell populations with in vivo clonogenic, leukemia initiating and propagating properties in xenograft models using immunocompromised mice. The very favorable B-lineage leukemia/lymphoma vs. normal tissue expression profile of CD19 and its association with stemness properties of leukemic B-cell precursor populations make it an attractive molecular target for biotherapy in relapsed ALL [59][60][61]. Several hundred thousand CD19 molecules located on the surface of each B-lineage leukemia/lymphoma cell are rapidly internalized upon ligation with anti-CD19 mAb or immunoconjugates [59], [62].…”

“…The very favorable B-lineage leukemia/lymphoma vs. normal tissue expression profile of CD19 and its association with stemness properties of leukemic B-cell precursor populations make it an attractive molecular target for biotherapy in relapsed ALL [59][60][61]. Several hundred thousand CD19 molecules located on the surface of each B-lineage leukemia/lymphoma cell are rapidly internalized upon ligation with anti-CD19 mAb or immunoconjugates [59], [62]. CD19 has tyrosine-based internalization motifs in its cytoplasmic domain that were predicted to bind the clathrin adaptor AP-2 [59][60][61].…”