Prostate Cancer

Recently, aptamers have been used to target nanoparticulate systems to prostate-specific membrane antigen, a known prostate cancer tumor marker. A model drug, rhodamine-labeled dextran, was encapsulated in PEGylated poly(lactic acid) nanoparticles, which were subsequently surface modified with a prostate specific RNA aptamer (A10). Binding of the aptamer nanoparticles to LNCaP cells expressing prostate specific membrane antigen in vitro was significantly enhanced when compared to a control of nontargeted particles. Additionally, very low binding was seen on nonprostate specific membrane antigen expressing cells (PC3). The nanoparticles were shown to both target and be taken up by the prostate cancer epithelial cells. This evidence points to the conclusion that this novel aptamer-based, targeted nanoparticle delivery approach can be effective.73 Gao and collaborators report the use of quantum dots (QD) for in vivo targeting of prostate cancer and imaging of tumors.7 The core-shell CdSe-ZnS quantum dots contain tri-n-octylphosphine oxide (TOPO) that binds to a covering of high molecular weight ABC triblock copolymer of polybutylacrylate, polyethylacrylate, polymethacrylic acid, and an 8-carbon alkyl side chain. The complex is functionalized with PEG molecules and monoclonal antibodies to prostate-specific membrane antigen. Specific binding was shown for prostate cancer lines whereas low binding was seen to normal cells. The QD-antibody formulations were studied in vivo in a mouse model human prostate cancer. The nanoparticles were shown to target to the tumor both by passive and active antibody targeting. Sensitive and multicolor fluorescence imaging of cancer cells in vivo was

TABLE 12.1

Targeting Systems Utilizing Antibodies Currently in Use to Treat Cancer

Mechanism

Antibody Target

Trade Name

TABLE 12.1

Targeting Systems Utilizing Antibodies Currently in Use to Treat Cancer

Mechanism

Antibody Target

Trade Name

Agonist activity

CD40, CD137

Various

Antagonist activity

CTLA4

MDX-010

Angiogenesis inhibition

VEGF

Avastin™

Antibody-dependent cell-mediated cytotoxicity

CD20

Rituxan®, HuMax-CD20, Zevalin

Inhibition of binding of extracellular growth signals

HER-2/neu

Herceptin

Receptor blockage

EGF receptor

HuMax-EGFr

Toxin-mediated killing

CD33

Mytotarg®

Disruption signaling

HER-2/neu

Pertuzumab (2C4)

Complement-dependent cytotoxicity

CD20

Rituxan®, HuMax-CD20

Blockage ligand binding

EGF receptor

Erbutix™

Antibody-dependent lysis of leukemic cells following

CD52

Campath®

cell binding Inhibits phosphorilation of tyrosine kinases

EGF receptor

Iressa cell binding Inhibits phosphorilation of tyrosine kinases

EGF receptor

Iressa

accomplished in this study. Nonspecific uptake was seen in the liver and spleen with little or no uptake in other organs.

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