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, LeMoyne Habimana-Griffin, Monica Shokeen, Xinming Xu, Katherine Weilbaecher, Michael Tomasson, Gregory Lanza, John F. DiPersio and Samuel Achilefu ()
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Nalinikanth Kotagiri: Washington University School of Medicine
Matthew L. Cooper: Washington University School of Medicine
Michael Rettig: Washington University School of Medicine
Christopher Egbulefu: Washington University School of Medicine
Julie Prior: Washington University School of Medicine
Grace Cui: Washington University School of Medicine
Partha Karmakar: Washington University School of Medicine
Mingzhou Zhou: Washington University School of Medicine
Xiaoxia Yang: Washington University School of Medicine
Gail Sudlow: Washington University School of Medicine
Lynne Marsala: Washington University School of Medicine
Chantiya Chanswangphuwana: Washington University School of Medicine
Lan Lu: Washington University School of Medicine
LeMoyne Habimana-Griffin: Washington University School of Medicine
Monica Shokeen: Washington University School of Medicine
Xinming Xu: Washington University School of Medicine
Katherine Weilbaecher: Washington University School of Medicine
Michael Tomasson: Washington University School of Medicine
Gregory Lanza: Washington University School of Medicine
John F. DiPersio: Washington University School of Medicine
Samuel Achilefu: Washington University School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-017-02758-9

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