Sequential combination therapy of ovarian cancer with degradable N-(2-hydroxypropyl)methacrylamide copolymer paclitaxel and gemcitabine conjugates

Single Molecule localization super resolution imaging offers the ability to track the distribution of specific molecule types throughout cells and tissues. In this paper, the authors utilized that potential in order to evaluate the intracellular mechanism of delivery of therapeutic agents for cancer treatment.

Biopolymers are being increasingly used as drug carriers in cancer treatment. The authors characterize the effect of second-generation high-molecular weight backbone-degradable HPMA copolymer carriers on A2780 human ovarian carcinoma xenografts. Three dimensional single molecule localization super-resolution imaging was used to elucidate conjugate internalization and drug release by using FITC-P-Cy5 as a model conjugate. Super-resolution imaging showed that FITC-P-Cy5 was internalized via endocytosis and colocalized with lysosomes and late endosomes. FITC and Cy5 signals were colocalized initially. Over time, Cy5 molecules were located at further distances from FITC due to the release of Cy5 from polymer side chains.

The super-resolution images indicate that bond cleavage occurs in the lysosomes and that the functional payload can diffuse into the cytoplasm. Besides shedding light on the internal mechanisms of a particular type of drug delivery system, it’s an excellent example of how single molecule localization super-resolution imaging can be used to track the fate of specific molecule types.

DOI: 10.1073/nature.1406233111