Carrier-free nanomedicines self-assembled from palbociclib dimers and Ce6 for enhanced combined chemo-photodynamic therapy of breast cancer

Palbociclib is the world's first CDK4/6 kinase inhibitor to be marketed. However, it is not effective in the treatment of triple negative breast cancer (TNBC) due to the loss of retinoblastoma protein expression. Thus, combinatorial chemotherapy is indispensable for TNBC treatment. Herein, a carrier-free nanomedicine self-assembled from palbociclib dimers and Ce6 for enhanced combined chemo-photodynamic therapy of breast cancer is reported. The dimeric prodrug (Palb-TK-Palb) was synthesized by conjugating two palbociclib molecules to the connecting skeleton containing a ROS-responsive cleavable thioketal bond. The Palb-TK-Palb/Ce6 NP co-delivery nanoplatform was prepared through the self-assembly of Palb-TK-Palb, Ce6 and DSPE-PEG2000. This novel carrier-free formulation as an efficient therapeutic agent showed efficient therapeutic agent loading capacity, high cellular uptake and huge therapeutic performance against breast cancer cells. The results of in vitro antitumor activity and cell apoptosis demonstrated that Palb-TK-Palb/Ce6 NPs presented a better inhibitory effect on the growth of cancer cells due to the palbociclib and Ce6 co-delivery nanomedicine-mediated synergistic chemo-photodynamic therapy. The IC50 values of Palb-TK-Palb/Ce6 NPs in MDA-MB-231 cells were around 1-2 mu M and 2 mu M and the Palb-TK-Palb/Ce6 NPs showed an increase in apoptosis up to 91.9%. In general, the carrier-free nanomedicine self-assembled from palbociclib dimers and Ce6 provides options for combinatorial chemo-photodynamic therapy.

Automated summary

Palbociclib, the first marketed CDK4/6 kinase inhibitor, is not effective in treating triple negative breast cancer (TNBC). Therefore, combinatorial chemotherapy is necessary for TNBC treatment. In this study, a carrier-free nanomedicine was developed using palbociclib dimers and Ce6 for enhanced combined chemo-photodynamic therapy of breast cancer. The nanoplatform showed efficient therapeutic agent loading capacity, high cellular uptake, and significant therapeutic performance against breast cancer cells. The results demonstrated that the nanomedicine presented a better inhibitory effect on cancer cell growth through synergistic chemo-photodynamic therapy.