Radionuclides transform chemotherapeutics into phototherapeutics for precise treatment of disseminated cancer

Nalinikanth Kotagiri, Matthew L. Cooper, Michael Rettig, Christopher Egbulefu, Julie Prior, Grace Cui, Partha Karmakar, Mingzhou Zhou, Xiaoxia Yang, Gail Sudlow, Lynne Marsala, Chantiya Chanswangphuwana, Lan Lu, Le Moyne Habimana-Griffin, Monica Shokeen, Xinming Xu, Katherine Weilbaecher, Michael Tomasson, Gregory Lanza, John F. DipersioSamuel Achilefu

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Most cancer patients succumb to disseminated disease because conventional systemic therapies lack spatiotemporal control of their toxic effects in vivo, particularly in a complicated milieu such as bone marrow where progenitor stem cells reside. Here, we demonstrate the treatment of disseminated cancer by photoactivatable drugs using radiopharmaceuticals. An orthogonal-targeting strategy and a contact-facilitated nanomicelle technology enabled highly selective delivery and co-localization of titanocene and radiolabelled fluorodeoxyglucose in disseminated multiple myeloma cells. Selective ablation of the cancer cells was achieved without significant off-target toxicity to the resident stem cells. Genomic, proteomic and multimodal imaging analyses revealed that the downregulation of CD49d, one of the dimeric protein targets of the nanomicelles, caused therapy resistance in small clusters of cancer cells. Similar treatment of a highly metastatic breast cancer model using human serum albumin-titanocene formulation significantly inhibited cancer growth. This strategy expands the use of phototherapy for treating previously inaccessible metastatic disease.

Original languageEnglish
Article number275
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

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