title: Local triple-combination therapy results in tumour regression and prevents recurrence in a colon cancer model.
abstract: Conventional cancer therapies involve the systemic delivery of anticancer agents that neither discriminate between cancer and normal cells nor eliminate the risk of cancer recurrence. Here, we demonstrate that the combination of gene, drug and phototherapy delivered through a prophylactic hydrogel patch leads, in a colon cancer mouse model, to complete tumour remission when applied to non-resected tumours and to the absence of tumour recurrence when applied following tumour resection. The adhesive hydrogel patch enhanced the stability and provided local delivery of embedded nanoparticles. Spherical gold nanoparticles were used as a first wave of treatment to deliver siRNAs against Kras, a key oncogene driver, and rod-shaped gold nanoparticles mediated the conversion of near-infrared radiation into heat, causing the release of a chemotherapeutic as well as thermally induced cell damage. This local, triple-combination therapy can be adapted to other cancer cell types and to molecular targets associated with disease progression.
authors.affiliation: Massachusetts Institute of Technology, Institute for Medical Engineering and Science, Cambridge, Massachusetts 02139, USA.|School of Engineering and Materials Science, Queen Mary University of London, London E1 4NS, UK.
authors.forename: João
authors.identifier: 0000-0001-8422-6792
authors.initials: J
authors.lastname: Conde
authors.affiliation: Massachusetts Institute of Technology, Institute for Medical Engineering and Science, Cambridge, Massachusetts 02139, USA.
authors.forename: Nuria
authors.initials: N
authors.lastname: Oliva
authors.affiliation: Massachusetts Institute of Technology, Institute for Medical Engineering and Science, Cambridge, Massachusetts 02139, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Massachusetts Institute of Technology, Institute for Medical Engineering and Science, Cambridge, Massachusetts 02139, USA.|Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.|Department of Medicine, Division of Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Natalie
authors.initials: N
authors.lastname: Artzi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D015316:Genetic Therapy; D006046:Gold / Q000737:chemistry; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry; D051379:Mice; D010789:Phototherapy; D016283:Proto-Oncogene Proteins p21(ras) / Q000172:deficiency / Q000235:genetics; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: C117307:KRAS protein, human; D034741:RNA, Small Interfering; D006046:Gold; D016283:Proto-Oncogene Proteins p21(ras)