Abstract
Liposomal doxorubicin (L-DOX) is a popular drug formulation for the treatment of several cancer types (e.g., recurrent ovarian cancer, metastatic breast cancer, multiple myeloma, etc.), but poor nuclear internalization has hampered its clinical applicability so far. Therefore, novel drug-delivery nanosystems are actively researched in cancer chemotherapy. Here we demonstrate that DOX-loaded graphene oxide (GO), GO-DOX, exhibits much higher anticancer efficacy as compared to its L-DOX counterpart if administered to cellular models of breast cancer. Then, by a combination of live-cell confocal imaging and fluorescence lifetime imaging microscopy (FLIM), we suggest that GO-DOX may realize its superior performances by inducing massive intracellular DOX release (and its subsequent nuclear accumulation) upon binding to the cell plasma membrane. Reported results lay the foundation for future exploitation of these new adducts as high-performance nanochemotherapeutic agents.
Highlights
The anthracycline doxorubicin (DOX) is a common first-line therapy for numerous human pathological conditions such as breast cancer, ovarian cancer, multiple myeloma and Kaposi’s sarcoma
graphene oxide (GO) leads to a significant increase in cell mortality with respect to approved Liposomal doxorubicin (L-DOX)
We see this proof of concept work as being part of a future workflow for all bionanoscience, nanomedicine and other areas in which shedding light on the mechanisms of GO-mediated drug delivery is fundamental to fully exploit its potential
Summary
The anthracycline doxorubicin (DOX) is a common first-line therapy for numerous human pathological conditions such as breast cancer, ovarian cancer, multiple myeloma and Kaposi’s sarcoma. The aim was, in particular, at exploiting the nanocarrier intrinsic ability to protect the drug from degradation, prolong its circulation lifetime, reduce drug dose, having a positive impact on drug biodistribution, pharmacokinetics and therapeutic efficacy [3]. In this regard, liposomal DOX (L-DOX) in all its variants (e.g., Doxil®, Doxoves® and LipoDox®) is a paradigmatic example. Its interaction with nuclear DNA could be disadvantaged compared to that of its monomeric counterpart Based on all these considerations, it is clear that novel nanocarriers that are capable of overcoming the limitations of standard L-DOX formulations are highly desirable in the field. Results reported here pave the way to future applications of GO in drug delivery research
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