Conjugating doxorubicin to polymannose: a new strategy for target specific delivery to lung cancer cells

Abstract

As mannose receptors are known to be over-expressed in cancer cells, we synthesized polymannose-doxorubicin (PM-DOX) conjugates with the objective of targeting the drug to cancer cells. DOX was conjugated to oxidized PM through Schiff’s linkages to obtain PM-DOX conjugates. In order to examine the superior targeting efficacy of PM-DOX conjugate, sodium alginate (SA) was conjugated to DOX by similar chemistry and compared with PM-DOX conjugate. The cytotoxicity of the conjugates was investigated in A549 cell lines using MTT Assay and the cell uptake and retention studies, were performed using flow cytometry and cell imaging. In vitro drug release studies with both PM-DOX and SA-DOX conjugates showed an initial burst release of DOX up to 37–39% at 1 h, followed by a steady release up to 58–62% at 24 h in human plasma while negligible release was observed in phosphate buffered saline. The conjugates exhibited negligible hemolytic potential to human erythrocytes compared to free DOX. The PM-DOX conjugate showed better cytotoxic potential against A549 cells at lower concentration (equivalent to 0.27 μg/mL of DOX) at 72 h compared to free DOX and SA-DOX conjugate. Further, PM-DOX conjugate showed enhanced uptake by the cells in comparison with SA-DOX conjugate thereby confirming the target specificity of PM to the cancer cells.

Keywords:

• Polymannose
• doxorubicin
• flow cytometry
• hemolysis
• anti-cancer

Acknowledgments

APF thanks IIT Madras for Institute Post-Doctoral Fellowship. The authors thank the Sophisticated Analytical Instrument Facility (SAIF) of IIT Madras for the characterization studies, Prof. Rayala S. Kumar for his help with the cell culture studies.

Disclosure statement

No potential conflict of interest was reported by the authors.