The Noninvasive Treatment for Sentinel Lymph Node Metastasis by Photodynamic Therapy Using Phospholipid Polymer as a Nanotransporter of Verteporfin

Abstract

Aim. The usefulness of photodynamic therapy (PDT) for treating sentinel lymph node (SLN) metastasis was evaluated. Materials and Methods. Verteporfin, a hydrophobic photosensitizer, forms a soluble aggregate with poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (PMB). The concentrations of verteporfin were determined by measuring the fluorescence emitted at 700 nm. Seven days after the inoculation of A431 cells at the forearm of BALB/c nude mice, PMB-verteporfin was injected at dorsum manus and 75 J of light energy was delivered for 1 minute. Fifty-three mice were randomly assigned to the combination of PMB-verteporfin injection and light exposure, light exposure alone, PMB-verteporfin injection alone, and no treatment groups. Ten days after PDT, brachial lymph nodes, which were considered as SLNs, were harvested and evaluated. Results. The concentration of verteporfin in SLN was significantly higher than other organs. The combination of PMB-verteporfin injection and light exposure group significantly reduced the SLN metastasis (13%) comparing with no treatment group (52%), light exposure alone group (57%), and PMB-verteporfin injection alone group (46%). Conclusions. These data suggested that PDT using PMB as a nanotransporter of verteporfin could be a minimally invasive treatment of SLN metastasis in breast cancer and represent a potential alternative procedure to SLNB.

Mechanistic Insights into Photodynamic Regulation of Adenosine 5′-Triphosphate-Binding Cassette Drug Transporters

“…An excellent example of a clinical application of photochemistry is photodynamic therapy (PDT), which involves the light activation of photosensitizers to generate reactive oxygen species to treat various diseases such as actinic keratosis, non-small cell lung cancer, and head and neck cancer. − In addition to treating primary diseases originating in a particular part of the body, PDT can be leveraged to target disseminated diseases with appropriate drug delivery carriers, targeting moieties, and optical technologies. For example, a study by Shimada et al combined a phospholipid polymer with a photosensitizer to treat sentinel lymph node metastasis of breast cancer . In another study, intralipid infusion was used to scatter light for activation of photosensitizers in the peritoneal cavity for the treatment of disseminated cancer. , Many photosensitizers that have been successfully employed in the clinic, including chlorin e6, protoporphyrin IX, and benzoporphyrin derivative (BPD, aka.…”

Establishment of a model of sentinel lymph node metastasis using immunodeficient swine

“…Specifically, photodynamic therapy (PDT) has attracted attention as a minimally invasive treatment. A study of a rodent model of lymph node metastasis employed PDT 25 . In this study, A431 cells were injected to the forelimbs of BALB/c nude mice to develop lymph node metastasis, 2-methacryloyloxyethyl phosphorylcholine -verteporfin was subsequently injected at the dorsum manus, and 75 J of light was delivered to the skin.…”

“…There are several limitations in the present study. We used A431 cells as we did in previous studies 23,25 . To better assess the clinical relevance of our model, we plan to use cell lines or primary tumour cells derived from other cancers (i.e.…”

“…Studies of SLNs have been performed using healthy rodents or large animals with non-metastatic tumours 19–22 . We developed a rodent model of lymph node metastasis that enabled us to show that magnetic particles are useful for identifying SLNs 23 and that photodynamic therapy is effective for treating lymph node metastasis 24,25 . However, the small size of rodents is insufficient for measuring lymph flow, applying novel imaging methods, determining the optimum dose of a therapeutic agent and the optimum treatment protocol.…”

Radiodynamic Therapy Using TAT Peptide-Targeted Verteporfin-Encapsulated PLGA Nanoparticles

“…The peak size of the PLGA-VP-TAT NPs in PBS with and without 10% FBS showed a slight increase during the first 4 h but then remained constant for the next few 48 h (Figure 1e), indicating that there was no significant aggregation in biological media. The % release of VP from the PLGA-VP NPs in PBS suspension at 37 • C was plotted as a function of time (Figure 1f), and showed that, after some initial release in the first 4 h, >95% of the VP remained trapped within the NPs (Figure 1e), likely due to VP being highly hydrophobic with a low affinity for the hydrophilic environment outside the PLGA matrix [41]. This drug release profile is consistent with our previous findings [17].…”