213P - Prominin-1-targeted apoferritin nanoparticle carrying irinotecan as a novel radiosensitizer for colorectal cancer stem-like cells

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Translational Research
Presenter Jenny Ling-Yu Chen
Citation Annals of Oncology (2016) 27 (suppl_9): ix53-ix67. 10.1093/annonc/mdw581
Authors J.L. Chen1, Y. Tsai2, Y. Huang2, S. Kuo3, M. Shieh2
  • 1Oncology, National Taiwan University Hospital, 100 - Taipei/TW
  • 2Institute Of Biomedical Engineering, Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, 100 - Taipei/TW
  • 3Department Of Oncology, National Taiwan University Hospital, 100 - Taipei/TW

Abstract

Background

Resistance of cancer stem cells to radiotherapy remains a major obstacle to successful cancer management. Prominin-1 (PROM1) is a marker for cancer stem cells. Nanoparticle (NP) chemotherapeutics have great potential as radiosensitizers. They demonstrate preferential accumulation in tumors and are able to target cancers and cancer stem-like cells through cancer cell-specific molecular ligands, making them uniquely suited for chemoradiation therapy. We aimed to develop a PROM1-targeted NP carrying irinotecan (IRI) and evaluate its utility as a radiosensitizer.

Methods

Using a biocompatible apoferritin NP, we engineered a PROM-1 targeted NP (PROM1-NP) carrying IRI. These NPs have sizes of 17.23 ±0.2 nm and surface charges of -13.5 ± 0.2 mV. The synergistic effect of the NPs and irradiation were evaluated in vitro in PROM-1–overexpressing HCT-116 colorectal cancer cell lines using a cell viability assay, and in vivo, in ectopic tumor models using the colony formation assay.

Results

PROM1-NPs demonstrated higher intracellular uptake than that of non-targeted NPs or IRI alone. Treatment with PROM1-NPs decreased HCT-116 cell proliferation in a dose- and time-dependent manner. In vitro radiosensitization using irradiation revealed that PROM1-NP was significantly more effective as a radiosensitizer than NP or IRI. The growth of HCT-116 tumor xenografts was markedly slower following treatment with the combination of PROM1-NP plus irradiation than following treatment with NP plus irradiation or IRI plus irradiation, suggesting that PROM1-NP is more effective as a radiosensitizer than IRI or NP in vivo.

Conclusions

PROM1-NP is an effective radiosensitizer in PROM-1–overexpressing colorectal cancer cell lines both in vitro and in vivo. Molecular-targeted NPs have great potential as radiosensitizers.

Clinical trial indentification

Legal entity responsible for the study

National Taiwan University Hospital

Funding

Ministry of Science and Technology (MST, Taiwan, under contract of MST 105-2314-B-002-022-)

Disclosure

All authors have declared no conflicts of interest.