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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 | Samuel Achilefu
Nature communications | 2018

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.

Pubmed ID: 29348537

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: P50 CA094056
  • Agency: NIBIB NIH HHS, United States
    Id: R01 EB008111
  • Agency: NCI NIH HHS, United States
    Id: R50 CA211466
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL113392
  • Agency: NIBIB NIH HHS, United States
    Id: R01 EB021048
  • Agency: NCI NIH HHS, United States
    Id: R01 CA194552
  • Agency: NCI NIH HHS, United States
    Id: R01 CA171651
  • Agency: NCI NIH HHS, United States
    Id: R01 CA216840
  • Agency: NCI NIH HHS, United States
    Id: R01 CA152329
  • Agency: NCI NIH HHS, United States
    Id: U54 CA199092

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Jackson Laboratory (tool)

RRID:SCR_004633

An independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.

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