John Garner

PLGA-PEG-NHS and mPEG-PLGA from PolySciTech used in development of peptide-targeting nanoparticle for triple-negative breast cancer therapy

Blog Post created by John Garner on Feb 19, 2018

Bressler, 2018 polyscitech triple-negative breast cancer nanoparticles.png

Targeted medicine is better described as ‘retentive’ or possibly ‘adhesive’ medicine. Any molecule which enters the human blood-stream is rapidly circulated throughout all parts of the entire body. Conventional medicines have a very limited and specific mechanism of action, which is why their effects are only experienced in the disease-state locations. That being said, exceeding the dosage on conventional drugs can cause toxic effects and the most common example of this is acetaminophen, a headache medicine, which in excessive doses can cause toxicity in the liver. Amongst medicinal therapies, chemotherapy is unique in that it is comprised of compounds known to either kill, or prevent the replication of, human cells and it is dosed at a concentration known to be toxic. The ‘theory of action’ is that, since the cancer is growing faster than all other tissues, it will be more affected than other tissues. Unfortunately, all cells are affected, which is why chemotherapy patients lose their hair and have several other side-effects. Although medicine in the blood-stream will flow to all parts of the human body, use of nanoparticles or other delivery systems which have a specific binding ligand will encourage the nanoparticles to be retained at the site of specific cells through ligand binding mechanisms (e.g. the nanoparticles flow everywhere, but they ‘stick’ to the cancer by ligand binding) Recently, researchers from Johns Hopkins University and AsclepiX Therapeutics used AI111 (PLGA-PEG-NHS) and AK037 (mPEG-PLGA) from PolySciTech ( to create peptide-decorated nanoparticles for adhesion to triple-negative breast cancer. This research holds promise for improved treatments for this drug-resistant and highly invasive form of cancer. Read more: Bressler, Eric M., Jayoung Kim, Ron B. Shmueli, Adam C. Mirando, Hojjat Bazzazi, Esak Lee, Aleksander S. Popel, Niranjan B. Pandey, and Jordan J. Green. "Biomimetic peptide display from a polymeric nanoparticle surface for targeting and antitumor activity to human triple‐negative breast cancer cells." Journal of Biomedical Materials Research Part A (2018).


“Abstract: While poly(lactic-co-glycolic acid)-block-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) can encapsulate drug cargos and prolong circulation times, they show non-specific accumulation in off-target tissues. Targeted delivery of drugs to tumor tissue and tumor vasculature is a promising approach for treating solid tumors while enhancing specificity and reducing systemic toxicity. AXT050, a collagen-IV derived peptide with both antitumor and antiangiogenic properties, is shown to bind to tumor-associated integrins with high affinity, which leads to targeted accumulation in tumor tissue. AXT050 conjugated to PLGA-PEG NPs at precisely controlled surface density functions both as a targeting agent to human tumor cells and demonstrates potential for simultaneous antitumorigenic and antiangiogenic activity. These targeted NPs cause inhibition of adhesion and proliferation in vitro when added to human triple-negative breast cancer cells and microvascular endothelial cells through binding to integrin αVβ3. Furthermore, we find an in vivo biphasic relationship between tumor targeting and surface coating density of NPs coated with AXT050. NPs with an intermediate level of 10% peptide surface coating show approximately two-fold greater accumulation in tumors and lower accumulation in the liver compared to non-targeted PLGA-PEG NPs in a murine biodistribution model. Display of biomimetic peptides from NP surfaces to both target and inhibit cancer cells has the potential to enhance the activity of cancer nanomedicines.”