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. Dipersio; Samuel Achilefu

doi:10.1038/s41467-017-02758-9

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 journal › Article › peer-review

52 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 language	English (US)
Article number	275
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-02758-9
State	Published - Dec 1 2018
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Kotagiri, N., Cooper, M. L., Rettig, M., Egbulefu, C., Prior, J., Cui, G., Karmakar, P., Zhou, M., Yang, X., Sudlow, G., Marsala, L., Chanswangphuwana, C., Lu, L., Habimana-Griffin, L. M., Shokeen, M., Xu, X., Weilbaecher, K., Tomasson, M., Lanza, G., ... Achilefu, S. (2018). Radionuclides transform chemotherapeutics into phototherapeutics for precise treatment of disseminated cancer. Nature communications, 9(1), Article 275. https://doi.org/10.1038/s41467-017-02758-9

Kotagiri, N, Cooper, ML, Rettig, M, Egbulefu, C, Prior, J, Cui, G, Karmakar, P, Zhou, M, Yang, X, Sudlow, G, Marsala, L, Chanswangphuwana, C, Lu, L, Habimana-Griffin, LM, Shokeen, M, Xu, X, Weilbaecher, K, Tomasson, M, Lanza, G, Dipersio, JF & Achilefu, S 2018, 'Radionuclides transform chemotherapeutics into phototherapeutics for precise treatment of disseminated cancer', Nature communications, vol. 9, no. 1, 275. https://doi.org/10.1038/s41467-017-02758-9

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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.",

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AU - Cui, Grace

AU - Karmakar, Partha

AU - Zhou, Mingzhou

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AU - Lu, Lan

AU - Habimana-Griffin, Le Moyne

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AU - Xu, Xinming

AU - Weilbaecher, Katherine

AU - Tomasson, Michael

AU - Lanza, Gregory

AU - Dipersio, John F.

AU - Achilefu, Samuel

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N2 - 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.

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Radionuclides transform chemotherapeutics into phototherapeutics for precise treatment of disseminated cancer

Abstract

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