title: Targeted indocyanine-green-loaded calcium phosphosilicate nanoparticles for in vivo photodynamic therapy of leukemia.
abstract: Leukemia is one of the most common and aggressive adult cancers, as well as the most prevalent childhood cancer. Leukemia is a cancer of the hematological system and can be divided into a diversity of unique malignancies based on the onset of the disease as well as the specific cell lineages involved. Cancer stem cells, including recently identified leukemia stem cells (LSCs), are hypothesized to be responsible for cancer development, relapse, and resistance to treatment, and new therapeutics targeting these cellular populations are urgently needed. Nontoxic and nonaggregating calcium phosphosilicate nanoparticles (CPSNPs) encapsulating the near-infrared fluoroprobe indocyanine green (ICG) were recently developed for diagnostic imaging and drug delivery as well as for photodynamic therapy (PDT) of solid tumors. Prior studies revealed that specific targeting of CPSNPs allowed for enhanced accumulation within breast cancer tumors, via CD71 targeting, or pancreatic cancer tumors, via gastrin receptor targeting. In the present study, ICG-loaded CPSNPs were evaluated as photosensitizers for PDT of leukemia. Using a novel bioconjugation approach to specifically target CD117 or CD96, surface features enhanced on leukemia stem cells, in vitro ICG-CPSNP PDT of a murine leukemia cell line and human leukemia samples were dramatically improved. Furthermore, the in vivo efficacy of PDT was dramatically enhanced in a murine leukemia model by utilizing CD117-targeted ICG-CPSNPs, resulting in 29% disease-free survival. Altogether, this study demonstrates that leukemia-targeted ICG-loaded CPSNPs offer the promise to effectively treat relapsing and multidrug-resistant leukemia and to improve the life of leukemia patients.
authors.affiliation: Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA. bmb14@psu.edu
authors.forename: Brian M
authors.initials: BM
authors.lastname: Barth
authors.forename: Erhan
authors.initials: E
authors.lastname: I Altinoğlu
authors.forename: Sriram S
authors.initials: SS
authors.lastname: Shanmugavelandy
authors.forename: James M
authors.initials: JM
authors.lastname: Kaiser
authors.forename: Daniza
authors.initials: D
authors.lastname: Crespo-Gonzalez
authors.forename: Nicole A
authors.initials: NA
authors.lastname: DiVittore
authors.forename: Christopher
authors.initials: C
authors.lastname: McGovern
authors.forename: Trevor M
authors.initials: TM
authors.lastname: Goff
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Keasey
authors.forename: James H
authors.initials: JH
authors.lastname: Adair
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Loughran
authors.forename: David F
authors.initials: DF
authors.lastname: Claxton
authors.forename: Mark
authors.initials: M
authors.lastname: Kester
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002130:Calcium Phosphates / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D018450:Disease Progression; D004705:Endocytosis; D005260:Female; D006801:Humans; D007208:Indocyanine Green / Q000737:chemistry*; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D015203:Reproducibility of Results; D017640:Silicates / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use*; D026082:Singlet Oxygen / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D014408:Biomarkers, Tumor; D002130:Calcium Phosphates; D017319:Photosensitizing Agents; D017640:Silicates; C499768:silica-calcium phosphate nanocomposite; D026082:Singlet Oxygen; D019009:Proto-Oncogene Proteins c-kit; D007208:Indocyanine Green