Chung, Seung Woo Choi, Jeong Uk Cho, Young Seok Kim, Ha Rin Won, Tae Hyung Dimitrion, Peter Jeon, Ok-Cheol Kim, Seong Who Kim, In-San Kim, Sang Yoon Byun, Youngro 2024-01-19T22:30:56Z 2024-01-19T22:30:56Z 2021-09-03 2018-07 2198-3844 https://pubs.kist.re.kr/handle/201004/121191 Tumor heterogeneity is associated with the therapeutic failures of targeted therapies. To overcome such heterogeneity, a novel targeted therapy is proposed that could kill tumor populations with diverse phenotypes by delivering nonselective cytotoxins to target-positive cells as well as to the surrounding tumor cells via a recurrent bystander killing effect. A representative prodrug is prepared that targets integrin alpha v beta 3 and releases cytotoxins upon entering cells or by caspase-3. This allows the prodrug to kill integrin alpha v beta 3-positive cells and upregulate caspase-3, which in turn, activates the prodrug to release a cytotoxin that could subsequently diffuse into and kill the neighboring tumor cells. Apoptotic cells further upregulate and release caspase-3, which activate more prodrugs leading to another round of adjacent cell death and caspase-3 release. Thus, the bystander killing effect could occur repeatedly, leading to augmented and widespread anticancer activity. This strategy provides an avenue that could advance the current targeted therapy. English WILEY TUMOR HETEROGENEITY DRUG-DELIVERY IN-VIVO DOXORUBICIN THERAPEUTICS EVOLUTION ESTERASE RGD Self-Triggered Apoptosis Enzyme Prodrug Therapy (STAEPT): Enhancing Targeted Therapies via Recurrent Bystander Killing Effect by Exploiting Caspase-Cleavable Linker Article 10.1002/advs.201800368 1 ADVANCED SCIENCE, v.5, no.7 ADVANCED SCIENCE 5 7 scie scopus 000439842100039 2-s2.0-85050165275 Chemistry, Multidisciplinary Nanoscience & Nanotechnology Materials Science, Multidisciplinary Chemistry Science & Technology - Other Topics Materials Science Article TUMOR HETEROGENEITY DRUG-DELIVERY IN-VIVO DOXORUBICIN THERAPEUTICS EVOLUTION ESTERASE RGD bystander killing effects cancer therapies caspases prodrugs target therapies