;Killing tumor cells while sparing their normal counterparts is a central challenge of cancer chemotherapy; discovery of new drugs, often validated using in vitro screening; has been supported by advances in the fields of chemical biology; medicinal chemistry, and diversity orienting synthesis to realize new classes of compounds acting against a variety of diseases.
But the study trying to target chemotherapy drugs to tumors by attaching antibodies that bind to proteins expressed on the cancer cells’ surfaces; by using cucurbituril to target therapies to a tumor. Cucurbituril is a pumpkin shaped molecule that can capture certain other chemicals within its central cavity. If the researchers could inject cucurbituril near a tumor; and then attach targeting chemicals to chemotherapy drugs; they might be able to retain the drugs at the tumor site through these interactions.
Target chemotherapy drugs
Then, the abnormally acidic microenvironment of the tumor would rupture the linkage between the drug and the targeting chemical, unleashing the therapy to kill cancer cells; Strategies to improve delivery of a drug to its target while limiting concomitant side effects remain in need of further discovery.
the researchers first injected a hydrogel containing cucurbituril under mice’s skin. They attached a dye to the targeting molecule so they could easily track it; and then injected that into the mice’s bloodstream; finding that 4.2% of the injected dye ended up in the hydrogel; which is much higher than previously reported antibody approaches. The mice quickly excreting the majority of the dye that is not bound to the hydrogel.
But when the team injecting the hydrogel adjacent to tumor xenografts in mice and then administered the cancer drug doxorubicin attached to the targeting molecule; the mice’s tumors showed much slower growth; and the mice had fewer side effects than those given unmodified doxorubicin.
The hydrogel persisted in the mice’s body for more than 45 days; which could allow repeated doses of chemotherapy drugs, or the use of different drugs with the same targeting molecule; This supramolecular homing axis extends the localization of small molecule payloads beyond injectable hydrogels; enabling targeting of modified biomaterials. This approach also has promising therapeutic utility; improving efficacy of a guest-modified chemotherapeutic agent in a tumor model.