A platelet-mimetic paradigm for metastasis-targeted nanomedicine platforms.
There is compelling evidence that, beyond their traditional role in hemostasis and thrombosis, platelets play a significant role in mediating hematologic mechanisms of tumor metastasis by directly and indirectly interacting with pro-metastatic cancer cells. With this rationale, we hypothesized that platelets can be an effective paradigm to develop nanomedicine platforms that utilize platelet-mimetic interaction mechanisms for targeted diagnosis and therapy of metastatic cancer cells. Here we report on our investigation of the development of nanoconstructs that interact with metastatic cancer cells via platelet-mimetic heteromultivalent ligand-receptor pathways. For our studies, pro-metastatic human breast cancer cell line MDA-MB-231 was studied for its surface expression of platelet-interactive receptors, in comparison to another low-metastatic human breast cancer cell line, MCF-7. Certain platelet-interactive receptors were found to be significantly overexpressed on the MDA-MB-231 cells, and these cells showed significantly enhanced binding interactions with active platelets compared to MCF-7 cells. Based upon these observations, two specific receptor interactions were selected, and corresponding ligands were engineered onto the surface of liposomes as model nanoconstructs, to enable platelet-mimetic binding to the cancer cells. Our model platelet-mimetic liposomal constructs showed enhanced targeting and attachment of MDA-MB-231 cells compared to the MCF-7 cells. These results demonstrate the promise of utilizing platelet-mimetic constructs in modifying nanovehicle constructs for metastasis-targeted drug as well as modifying surfaces for ex-vivo cell enrichment diagnostic technologies.
Department of Biomedical Engineering, Case Western Reserve University, 2071 Martin Luther King Drive, Cleveland, OH 44106, USA.
Christa L
CL
Modery-Pawlowski
Alyssa M
AM
Master
Victor
V
Pan
Gregory P
GP
Howard
Anirban
A
Sen Gupta
D000970:Antineoplastic Agents / Q000494:pharmacology; D040761:Biomimetic Materials / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D003630:Daunorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008081:Liposomes; D061986:MCF-7 Cells; D050997:Nanomedicine / Q000379:methods*; D012235:Rhodamines / Q000494:pharmacology
D000970:Antineoplastic Agents; D008024:Ligands; D008081:Liposomes; D012235:Rhodamines; D003630:Daunorubicin