1431696-61-5Relevant articles and documents
Riboflavin-targeted polymer conjugates for breast tumor delivery
Bareford, Lisa M.,Avaritt, Brittany R.,Ghandehari, Hamidreza,Nan, Anjan,Swaan, Peter W.
, p. 1799 - 1812 (2013)
Purpose: In breast cancer, a significant decrease in riboflavin (RF) serum levels and increase in RF carrier protein occurs, indicating a potential role of RF in disease progression. To evaluate RF's ability to serve as a targeting agent, mitomycin C (MMC)-conjugated N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers were synthesized and targeted to the RF internalization pathway in human breast cancer cells. Methods: Competitive uptake studies were used to determine specificity of RF-targeted conjugates, and an MTT assay established the IC50 for the conjugates. Endocytic mechanisms were investigated by confocal microscopy. Results: Studies revealed a high-affinity endocytic mechanism for RF-specific internalization of fluorescently-labeled conjugates in both MCF-7 and SKBR-3 cells, whereas folic acid-mediated endocytosis showed high specificity only in SKBR-3 cells. MMC internalization was significantly higher following nontargeted and RF-targeted MMC-conjugate administration compared to that of free MMC. Cytotoxic analysis illustrated potent IC 50 values for RF-targeted MMC conjugates similar to free MMC. Maximum nuclear accumulation of MMC resulted from lysosomal release from RF-targeted and nontargeted MMC-conjugates following 6 h incubations, unlike that of free MMC seen within 10 min. Conclusion: Targeting polymer-MMC conjugates to the RF internalization pathway in breast cancer cells enabled an increase in MMC uptake and nuclear localization, resulting in potent cytotoxic activity.
