Abstract
Background: Photodynamic therapy (PDT) is a promising technique for cancer treatment; however, low tissue permeability for irradiating light and insufficient photosensitizer (PS) accumulation in tumors limit its clinical potential. Nanoparticles are engineered to improve selective drug delivery to tumor sites, but its accumulation is highly variable between tumors and patients. Identifying PS accumulation peak in a personalized manner is crucial for therapeutic outcome. Magnetic nanoparticles (MNPs) provide opportunity for tracking drug accumulation in dynamics using non-invasive magnetic resonance imaging (MRI). The purpose of the study was to evaluate MNP loaded with PS as a theranostic tool for treating cancer in mice xenograft colon cancer models. Methods: MNPs coated with human serum albumin (HSA) were loaded with bacteriochlorine a. MRI, atomic emission spectroscopy (AES) and fluorescent imaging were used to study MNP and drug accumulation rates and dynamics in CT26 tumors. Tumor growth curves were evaluated in animals that received PDT at different time points upon MNP systemic injection. Results: Peak MNP accumulation in tumors was detected by MRI 60 min post injection (pi) and the data were verified by AES and fluorescent imaging. Up to 17% of injected dose/g of tissue was delivered to malignant tissues 24 h after injection. Consistent with MRI predicted drug accumulation peak PDT performed 60 min after intravenous injection was more efficient in inhibiting tumor growth than treatment scheduled 30 min and 240 min pi. Conclusions: PS loading on HAS-coated MNPs is a perspective approach to increase drug delivery to tumor site. Tracking for MNP accumulation by MRI can be used to predict drug concentration peak in tumors and to adjust PDT time scheduling for improved antitumor response.
Highlights
Photodynamic therapy (PDT) is an intensively developed approach for cancer treatment [1]
Activated PS molecule can transfer the energy via electrons or directly to O2 molecules with conversion of O2 molecules to superoxide radical of so-called singlet oxygen [8]
The aims of the study were: (1) to design a theranostic system based on Magnetic nanoparticles (MNPs) and bacteriochlorin derivatives that would meet aforementioned requirements for magnetic resonance imaging (MRI) guided photodynamic cancer therapy; and (2) to predict the most effective time for PDT by MNP tracking via MRI
Summary
Photodynamic therapy (PDT) is an intensively developed approach for cancer treatment [1]. Photodynamic therapy (PDT) is a promising technique for cancer treatment; low tissue permeability for irradiating light and insufficient photosensitizer (PS) accumulation in tumors limit its clinical potential. MRI, atomic emission spectroscopy (AES) and fluorescent imaging were used to study MNP and drug accumulation rates and dynamics in CT26 tumors. Results: Peak MNP accumulation in tumors was detected by MRI 60 min post injection (pi) and the data were verified by AES and fluorescent imaging. Consistent with MRI predicted drug accumulation peak PDT performed 60 min after intravenous injection was more efficient in inhibiting tumor growth than treatment scheduled 30 min and 240 min pi. Tracking for MNP accumulation by MRI can be used to predict drug concentration peak in tumors and to adjust PDT time scheduling for improved antitumor response
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