Engineered Nanoplatelets for Combination Therapy
Patent Number: Pending

Executive Summary:
  • Basis of Invention: Platelets interact with both tumor cells and blood vessels and allow tumor microenvironment inflammation that perpetuate tumor proliferation and invasion. Proteasome inhibitors used in the treatment of multiple myeloma, such as bortezomib, can be packed into nano-carriers that selectively target bone marrow multiple myeloma cells and sequentially unload chemotherapy cargo. 
  • How it works: Nanovehicles are produced using autologous platelet membranes of the patient. These platelet membranes contain antigens that specifically recognize the tumor cells in the same patient. P selectin is one of the antigens recognized by circulating tumor cells. The inner membrane of the nano-vehicle will contain antibodies depending on the type of tumor to treat; bortezomib is one example. The nanovehicle is made of platelet membrane-material comprising of an inner core comprising drug delivery matrix and an outer shell platelet membrane coating the inner core. The nanovehicle can contain multiple drugs and has been used to release other chemotherapy agents sequentially: TRAIL and Dox, and pembrozumab. Proof of principle for drug delivery of bortezomib has been demonstrated in preclinical studies on a multiple myeloma murine model
  • Lead Challenge Inventor: Zhen Gu 
  • Development Stage: In vivo data in animal models
  • Novelty: Novel targeted delivery of bortezomib for multiple myeloma
  • Clinical Applications:
    • Multiple Myeloma
 
General Description:
Platelet antigens represent a unique opportunity to target circulating tumor cells and antigen presenting cells. P selectin is a glycoprotein expressed by platelets and recognized by CD44 tumor cells. The use of this membrane in a nanovehicle with a matrix that can contain chemotherapy represents a novel way to target difficult tumor microenvironment by releasing proteasome inhibitor and NF-KB blocker bortezumab in multiple myeloma cancer cells resistant to current chemotherapy strategies.
 
Scientific Progress:
The method has advanced into the implementation and development of novel biomaterials from platelets to target selectively tumor microenvironment in bone marrow
 
Future Directions:
  • Phase I clinical studies to evaluate pharmacodynamics and pharmacokinetics
 
Strengths:
  • Promotes novel method to use platelet derived membranes and nanocarriers to release and target bone marrow multiple myeloma cells
 
Weaknesses:
  • Possible immunogenicity and poor bioavailability; continuous injections might be needed
 
Publications:
1: Hu Q, Qian C, Sun W, Wang J, Chen Z, Bomba HN, Xin H, Shen Q, Gu Z. Engineered Nanoplatelets for Enhanced Treatment of Multiple Myeloma and Thrombus. Adv Mater. 2016 Nov;28(43):9573-9580. doi: 10.1002/adma.201603463. Epub 2016 Sep 14. PubMed PMID: 27626769; PubMed Central PMCID: PMC5283718.
 
Inventor Bio: Zhen Gu
 http://www.bme.unc.edu/people/zhen-gu/