OCT 16, 2013 7:00 AM PDT

Novel strategies for the targeted delivery of anti-cancer drugs in bladder cancer CME and CE Credits Available

C.E. Credits: CE
Speaker

Abstract

The adjuvant therapy of choice for superficial bladder cancer is the intravesical instillation of live Mycobacterium bovis Bacillus Calmette-Guerin (BCG). In spite of the fact that this therapy is the most effective treatment for superficial bladder cancer, intravesical administration of BCG is associated with high local morbidity and the potential for systemic infection. Therefore, there is a need for the development of safer, less toxic approaches to fight this disease. Since fibronectin attachment protein (FAP) is a key element in BCG retention and targeting to cells, we hypothesize that this protein can be used as targeting agent to deliver cytotoxic cargo for the treatment of bladder tumors. Here we evaluated the ability of bladder tumor cells to bind and endocytose FAP via fibronectin-integrin complexes. We found that micro-aggregation induced by an anti-FAP polyclonal antibody accelerated FAP uptake by bladder tumor cells. FAP-FBN-Integrin complexes were determined to be internalized via a clathrin-independent, caveolae-dependent mechanism. Further, once in the endosomal compartment, FAP was targeted to the lysosomal compartment with negligible recycling to the plasma membrane. Importantly, we demonstrated that FAP micro-aggregation and internalization could also be triggered by multivalent Ni2+NTA-bearing liposomes. Overall, our studies validate the use of FAP as a targeting vector and provide the foundations for the design of more effective, less toxic bladder cancer therapeutics.


Show Resources
You May Also Like
MAY 17, 2022 9:00 AM PDT
MAY 17, 2022 9:00 AM PDT
Date: May 17, 2022 Time: 9:00am (PDT), 12:00pm (EDT), 8:00pm (CEST) Gene therapeutics have great potential to treat many severe diseases in an unprecedented, targeted manner. The biopharmace...
JUN 21, 2022 6:00 AM PDT
JUN 21, 2022 6:00 AM PDT
Date: June 21, 2022 Time: 6:00am (PDT), 9:00am (EDT), 3:00pm (CEST) The global understanding and practice of medicine is currently undergoing a revolutionary change. This shift to precision...
AUG 24, 2022 7:00 AM PDT
AUG 24, 2022 7:00 AM PDT
Date: August 24, 2022 Time: 7:00am (PDT), 10:00pm (EDT), 4:00pm (CEST) Light field microscopy was first introduced in 2006, and allows users to capture the 4D light field within the microsco...
AUG 16, 2022 11:00 AM PDT
AUG 16, 2022 11:00 AM PDT
Date: August 16, 2022 Time: 11:00am (PDT), 2:00pm (EDT), 8:00pm (CEST) Understanding genomic variation in the context of cancer is paramount to identifying disease drivers and informing pers...
JUN 28, 2022 7:00 AM PDT
JUN 28, 2022 7:00 AM PDT
Date: June 28, 2022 Time: 3:00pm (BST), 4:00pm (CET), 9:00am (CST), 7am (PST) Light-sheet microscopy is an extremely versatile imaging technique with a vast range of implementations that are...
JUN 29, 2022 7:00 AM PDT
JUN 29, 2022 7:00 AM PDT
Date: June 29, 2022 Time: 7:00am (PDT), 10:00am (EDT), 4:00pm (CEST) Imaging live cells is key to reveal their inner workings, dynamics, and function. Current technological advances in confo...
OCT 16, 2013 7:00 AM PDT

Novel strategies for the targeted delivery of anti-cancer drugs in bladder cancer CME and CE Credits Available

C.E. Credits: CE


Show Resources
Loading Comments...
Show Resources