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.

Hypericin-mediated photodynamic therapy induces apoptosis of myoloma SP2/0 cells depended on caspase activity in vitro

“…Additionally, it is reported that PDT exerts stronger cytotoxicity in chronic myeloid leukemia (CML) cells than normal granulocyte/ macrophage progenitors and PDT can eliminate CML cells from malignant-normal bone marrow mononuclear cells mixture [12]. PDT is becoming a promising therapeutic modality for hematological malignancies, such as leukemia [13], lymphoma [14] and MM [11].…”

The Concentration-Dependent Effects of Indocyanine Green on Retinal Function in the Electrophysiological ex vivo Model of Isolated Perfused Vertebrate Retina

“…Furthermore, severe damage was described after experimental macular surgery and application of 0.05% ICG solution to human donor eyes, presuming that ICG induces a phototoxic effect on the vitreoretinal surface resulting in a disruption of Müller cells [4,14,15]. Actually, since then this photosensitivity-related impact of ICG has been effectively used to treat different kinds of cancer experimentally and even clinically [16,17]. Moreover, a cell culture study demonstrated a dose-related increase in expression of apoptotic genes after cells were exposed to 2.5 mg/ml (0.25%) ICG solution and light, while it was not observed in controls and with a concentration of 0.25 mg/ml (0.025%) [7].…”

A Forecast of Targeting Leukemia Stem Cells by Nanomedicine

“…For example, gold-coated nanoshells can increase the sensitivity of CSCs to hyperthermia therapy in breast cancer xenograft model [108][109][110]. Barth et al reported Calcium Phosphosilicate Nanoparticles (CPSNPs) can encapsulate nearinfrared fluoroprobe Indocyanine Green (ICG) for diagnostic imaging and drug delivery.…”