TECHNOLOGY
TumorSelect® mechanism of action has potential indications for enhanced safety and efficacy of therapy by selective delivery to tumor tissues include the following cancers:
- Breast
- Colorectal
- Gastric
- Glioblastoma
- Leukemia
- Melanoma
- Non-small cell lung
- Ovarian
- Pancreatic
- Prostate
 
 
 
Biological Data:
TumorSelect® Mechanism of Action
Tumors are voracious consumers of cholesterol both as an energy source as well as a substrate for rapid cell membrane production.  Incorporating chemotherapeutics into pseudo LDL nanoparticles for delivery via overexpressed LDL receptors provides the opportunity for selective delivery of lipophilic chemotherapeutics to tumors compared with normal tissues.  Pseudo LDL particles can increase the utility of clinically approved chemotherapeutic agents by altering their PK/PD properties and dramatically raising the therapeutic indices of chemotherapies.
 
 
 
 
 
 
 
 
 
 
 
 
When injected, TumorSelect® pseudo LDL particles accumulate in tumor tissues by the EPR effect where they can be recognized by tumor cell LDL receptors.  The particles are internalized into endosomes where the acidic environment causes the breakdown of the particle and the release of free drug into the cytoplasm.
 
 
Sequential steps in the LDL receptor pathway of mammalian cancer cells showing uptake of TumorSelect®:
 
 
TumorSelect® particles increase the utility of clinically approved chemotherapeutic agents by:
–       Increasing plasma residence time
–       Targeting chemotherapeutic to cancer cells
–       Minimizing distribution into healthy tissues
–       Raising therapeutic indices
Proof of Concept for TumorSelect® Delivery of Paclitaxel:
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
Mice were divided into 6 groups (5 mice in each group). All test articles were administered to mice for the five consecutive days via intravenous (iv) injections. Group #1 received  drug-free lipid formulation ([0], open squares) and groups 2-5 received 23.7, 35.7, 47.1, and 72.6 mg/kg of formulated ART-207 (filled squares). Group #6 received 15 mg/kg of Paclitaxel (open circles). Effect is expressed as % of mean mouse weight assessed for each group prior to the first treatment at Day 0. Four of 5 mice died of toxicity in the paclitaxel group before day 10.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mice were divided into 6 groups (5 mice in each group). All test articles were administered to mice for the five consecutive days via intravenous (iv) injections. Group #1 received  drug-free lipid formulation ([0], open squares) and groups 2-5 received 23.7, 35.7, 47.1, and 72.6 mg/kg of formulated ART-207 (filled squares). Group #6 received 15 mg/kg of Cremophor EL/EtOH paclitaxel (open circles).  Effect is expressed as % of mean mouse weight assessed for each group prior to the first treatment at Day 0.
 
 
 
 
 
 
Mice were divided into 5 groups (10 mice in each group). All test articles were administered to mice for  five consecutive days via intravenous (iv) injections starting from day 0. Groups #2-4 received 105.2 (solid green), 78.9 (solid red), and 52.6 (solid yellow) mg/kg of formulated ART-207. Group #5 received  drug-free lipid formulation (black dotted line, open squares). Group #6 received 15 mg/kg of Cremophor EL/EtOH paclitaxel (blue dotted line, open circles).
 
 
 
 
 

Contact:

James D. McChesney, Ph.D.

147 County Road 245

Etta, MS  38627

Email: info@cloakedtherapeutics.com

 

 

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