Researchers from the Massachusetts General Hospital have discovered that tumor blood vessel normalization by antiangiogenesis drugs only improves the delivery of smaller nanotherapy molecules, but blocks the supply of larger nanomedicine molecules to cancer cells.
According to the study, the success of the combination of nanomedicines and antiangiogenesis drugs in treating cancer may rely on the size of the nanomedicines. The study results have been reported in the journal, Nature Nanotechnology.
Vikash P. Chauhan, the report’s lead author, informed that the study also demonstrated that the smaller nanomedicine is able to pierce tumors more effectively than larger nanomedicines, proving that smaller nanodrugs may be better for treating cancer. The tumor blood vessels, which are usually oversized, dislocated and leaky, not only prevent the delivery of anti-cancer drugs but also decrease the drugs’ ability to pierce tumors due to increase in pressure caused by plasma leakage in blood vessels.
Nanomedicines are essentially designed to leverage the abnormality of the tumor vessels. Their size is too large to pierce the pores of blood vessels of healthy tissues, thus decreasing their negative side effects. However, they are small enough to traverse the larger pores of tumor blood vessels.
In this study, the researchers investigated that whether antiangiogenesis drugs that are used for normalizing tumor blood vessels enhance or hinder the nanomedicine delivery to tumor cells. For this purpose, they created a mathematical model, which predicts that intratumor pressure gets increased due to the oversized pores of tumor blood vessels, thus preventing the delivery of drugs. The pore size reduction by antiangiogenesis treatment may reduce intratumor pressure, which in turn allows the delivery of molecules that are small enough to pass through the pores.
To test this model, the researchers used an antibody DC101 either with Doxil or with Abraxane in a mouse implanted with breast cancer. Doxil is anti-cancer medicine doxorubicin’s 100-nm version and Abraxane is paclitaxel’s 10-nm version. They observed that the antibody normalized the tumor blood vessels, which in turn enhanced the penetration of 12-nm drug molecules into cancer cells but not of 60-125 nm molecules.
According to Chauhan, the study results emphasize the necessity to develop smaller nanomedicines. It is equally important to find methods to enhance the delivery of existing larger nanomedicine.
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