Adhesive/adsorption switch on nanoparticles to increase tumor uptake and delay tumor clearance

Unmet Need
Effective drug delivery to solid tumors remains challenging. Outcome failure rates can reach 90% for current therapeutic approaches for solid tumors. The use of nanoparticles for the delivery of therapeutic agents can enhance the safety, pharmacokinetic profile, and bioavailability of administered drugs, leading to improved therapeutic tolerance and efficacy. These benefits are limited by the nanocarrier’s inability to uniformly penetrate the tumors, which can often have dysfunctional vasculature and lymph vessels, resulting in non-uniform drug microdistributions within the tumor volume and, therefore, in partial cell kill leading to tumor recurrence. Currently, there is no effective way to ensure full tumor infiltration following systemic administration of a therapeutic.
 
Technology Overview
Johns Hopkins researchers have developed an “adsorptive/adhesive switch” for drug delivery nanoparticles, which slows down their tumor-clearing kinetics. The switch allows for the promotion of ECM-adsorption of the nanoparticles while minimizing cell internalization resulting in longer residence times of the nanoparticles in the tumors. This property is utilized as follows. Given that these drug-loaded nanoparticles release the free drug (which is usually highly-diffusing, and, therefore, highly-penetrating) in the tumor interstitium, this adsorptive/adhesive switch results in maximizing the fraction of drug that can penetrate deep into the tumor enabling more uniform and more prolonged tumor infiltration to the free drug.

 
Stage of Development
The technology is at the preclinical stage of development. The switch-conjugated nanocarriers have been evaluated in vitro and in vivo in different mouse xenograft models of breast cancer. The researchers have confirmed that the primary effect of the adhesive switch is to increase tumor uptake and delay tumor clearance in vivo without affecting blood clearance kinetics of the nanoparticles. When loading nanocarriers with different therapeutics (chemotherapy, alpha-particle therapy), the researchers have also shown that the nanocarriers with the adhesive switch exhibit better inhibition of tumor growth and/or of metastatic spreading compared to nanocarriers without the adhesive switch.
 
Publications
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