Elucidating the cellular uptake mechanisms of heptamethine cyanine dye analogues for their use as an anticancer drug-carrier molecule for the treatment of glioblastoma.

The development of chemotherapies for glioblastoma is hindered by their limited bioavailability and toxicity on normal brain function. To overcome these limitations, we investigated the structure-dependent activity of heptamethine cyanine dyes (HMCD), a group of tumour-specific and BBB permeable near-infrared fluorescent dyes, in both commercial (U87MG) and patient-derived GBM cell lines. HMCD analogues with strongly ionisable sulphonic acid groups were not taken up by patient-derived GBM cells, but were taken up by the U87MG cell line. HMCD uptake relies on a combination of transporter uptake through organic anion-transporting polypeptides (OATPs) and endocytosis into GBM cells. The uptake of HMCDs was not affected by p-glycoprotein efflux in GBM cells. Finally, we demonstrate structure-dependent cytotoxic activity at high concentrations (EC50 : 1-100 µM), likely due to mitochondrial damage-induced apoptosis. An in vivo orthotopic glioblastoma model highlights tumour-specific accumulation of our lead HMCD, MHI-148, for up to 7 days following a single intraperitoneal injection. These studies suggest that strongly ionisable groups like sulphonic acids hamper the cellular uptake of HMCDs in patient-derived GBM cell lines, highlighting cell line-specific differences in HMCD uptake. We envisage these findings will help in the design and structural modifications of HMCDs for drug-delivery applications for glioblastoma.

A new proactive virtual resource center navigation model identifies patient risk factors to reduce barriers to cancer care during the COVID-19 pandemic.

PURPOSE: The COVID-19 pandemic has exacerbated cancer treatment disparities, including accessibility to resources. We describe the process and outcomes of a new proactive, virtual nurse-led, resource center navigation model enhanced by using volunteer patient navigators. Using known patient risk factors, this model provides interventions to reduce barriers to care, with an emphasis on non-English-speaking populations. METHODS: Patients were included if they (1) were in active cancer treatment and (2) had one or more known risk factors: distance from cancer hospital, needing complex care, 65 years or older, malignant hematological diagnosis, new treatment start, lives alone, non-English speaker, or a new hospital discharge. Nurse navigators triaged referrals to appropriate team members who identified and addressed barriers to care. RESULTS: The program engaged with 586 adult cancer patients over 1459 encounters. The most common risk factors included distance (59.7%), complex care (48.8%), and new treatment start (43.5%). The most common interventions were core education (69.4%), emotional support (61.2%), and education (35.7%). Statistical differences were found between Spanish-speaking (n = 118) and non-Spanish-speaking patients (n = 468). While Spanish-speaking patients had fewer risk factors (1.95 vs. 2.80, p ≤ .0001), they had nearly double the number of visits (4.27 vs. 2.04, p ≤ .0001) and 69% more interventions (8.26 vs. 4.90, p ≤ .0001). Many patients (42.7%) required follow-up visits. CONCLUSION: We successfully established a new navigation model for the resource center during the pandemic that identified and reduced barriers to care, particularly in the Spanish-speaking population.