Researchers have developed a prodrug-based amphiphilic polymer (PASA) for the codelivery of small molecule drugs and chemotherapeutic agents that targets cancer stem cells in solid tumors.
Description
The polymer self-assembles to form a small-sized nanocarrier that has a high loading capacity and has been shown to be highly effective in targeting and inhibiting tumor growth. High loading capacity and co-delivery to solid tumors has been demonstrated for chemotherapeutic agents, non-steroidal anti-inflammatory drugs (NSAID), and small molecule inhibitors.
This combination approach offers a novel way to harness the antitumor activity and immunity promoting features of COX inhibitors at a low and safe dose, especially in combination with chemotherapeutic agents. This could be a promising treatment approach for cancers with upregulated levels of Cyclooxygenase (COX)-1 and 2, including colorectal, breast, stomach, lung, and pancreatic cancers. COX-2 overexpression is also associated with a poor clinical outcome and higher rates of recurrence, as well as a low survival rate and resistance to immunotherapy. Development of a strategy to concentrate the COX inhibitors at tumor site can therefore provide an effective means of targeted treatment.
To date, the team demonstrated in animal cancer model that the combination of PASA loaded with doxorubicin (DOX) and co-delivered with an anti-PD-1 antibody leads to complete regression of some established tumors, even at suboptimal doses of PASA/DOX.
In addition, the team showed that simultaneously loading 5-aminosalicylic acid (5-ASA), cisplatin and MK-2206 (an AKT inhibitor) can overcome drug resistance in lung cancer through targeting cisplatin-induced stemness in lung cancer.
Advantages
·• Immunomodulation of tumors and tumor microenvironments in cancers with high levels of COX expression.
• Achieves COX inhibition at much lower doses, reducing the risk of negative side effects.
• Highest DOX loading capacity compared to existing carriers.
• Effective in targeting to tumor site.
• Can co-deliver both COX inhibitor and chemotherapeutic agents.
• May achieve drastic positive results in combination with immunotherapy treatment.
Invention Readiness
In vivo data
IP Status
https://patents.google.com/patent/US20230293553A1
