Near-Infrared Emitting Fluorophore-Doped Calcium Phosphate Nanoparticles for In Vivo Imaging of Human Breast Cancer

Abstract

Early detection is a crucial element for the timely diagnosis and successful treatment of all human cancers but is limited by the sensitivity of current imaging methodologies. We have synthesized and studied bioresorbable calcium phosphate nanoparticles (CPNPs) in which molecules of the near-infrared (NIR) emitting fluorophore, indocyanine green (ICG), are embedded. The ICG-CPNPs demonstrate exceptional colloidal and optical characteristics. Suspensions consisting of 16 nm average diameter particles are colloidally stable in physiological solutions (phosphate buffered 0.15 M saline (PBS), pH 7.4) with carboxylate or polyethylene glycol (PEG) surface functionality. ICG-doped CPNPs exhibit significantly greater intensity at the maximum emission wavelength relative to the free constituent fluorophore, consistent with the multiple molecules encapsulated per particle. The quantum efficiency per molecule of the ICG-CPNPs is 200% greater at 0.049 +/- 0.003 over the free fluorophore in PBS. Photostability based on fluorescence half-life of encapsulated ICG in PBS is 500% longer under typical clinical imaging conditions relative to the free dye. PEGylated ICG-CPNPs accumulate in solid, 5 mm diameter xenograft breast adenocarcinoma tumors via enhanced retention and permeability (EPR) within 24 h after systemic tail vein injection in a nude mouse model. Ex situ tissue imaging further verifies the facility of the ICG-CPNPs for deep-tissue imaging with NIR signals detectable from depths up to 3 cm in porcine muscle tissue. Our ex vivo and in vivo experiments verify the promise of the NIR CPNPs for diagnostic imaging in the early detection of solid tumors.

Combinatorial therapies improve the therapeutic efficacy of nanoliposomal ceramide for pancreatic cancer

“…Nanomaterials functionalized with polyethylene glycol (PEG), such as our ceramide-containing nanoliposome formulations, have the ability to passively accumulate within the leaky vasculature of tumors through enhanced permeation and retention. 49 Further improvements can possibly be achieved by selective tumor targeting by coupling antibodies, antibody fragments, peptides, peptide fragments or small ligands, to the PEGylations on the nanoparticles. 50 Altogether, second-generation nanoliposomes containing combinations of short-chain ceramide analogs, and other therapeutics designed to augment or complement the effects of ceramide, offer a promising solution for the treatment of highly resistant cancers such as pancreatic cancer.…”

Intraoperative Near-infrared Fluorescence Imaging with Novel Indocyanine Green-Loaded Nanocarrier for Spinal Metastasis: A Preliminary Animal Study

“…However, the strong binding of plasma proteins with ICG and its subsequent rapid clearance by the liver results in binding of ICG to the tumor only for a short duration after administration; thus, the use of ICG for tumor imaging applications is limited [17]. A potential approach to overcoming this disadvantage is delivering ICG in a nanocarrier that can provide increased stability and protection from nonspecific plasma protein binding and offer enhanced circulation time [18][19][20]. A novel nanocarrier, ICG-lactosome [21], which is a molecular assembly composed of hydrophobic poly(L-lactic acid) (PLLA) and hydrophilic poly(sarcosine) (PSar) amphiphilic block polydespsipeptide including ICG labeled PLLA in the hydrophobic inner core, provides good tumor imaging without accumulation to the liver.…”

Functionalized nanomaterials: their use as contrast agents in bioimaging: mono- and multimodal approaches

“…In addition, the use of mesoporous silica NPs enables the loading of additional functions into the resulting pores, for example, the imaging probes of sentinel lymph nodes (SLNs) known as the first defense against primary tumor metastasis [124] , sensing [125] , or a therapeutic agent capable of photothermal ablation (PTA) or a controlled drug release [126] . The covalent chemical grafting of the lanthanide complexes on the metal oxide NPs was also recently performed, and the introduction of two different lanthanides gave bimodal CAs [64,65,127] .…”