Abstract
The existing clinical protocols of hepatoma treatment require improvement of drug efficacy that can be achieved by harnessing nanomedicine. Porphyrin-based, paddle-wheel framework (PPF) structures were obtained and tested as dual-kinetic Sorafenib (SOR) nanocarriers against hepatoma. We experimentally proved that sloughing of PPF structures combined with gradual dissolving are effective mechanisms for releasing the drug from the nanocarrier. By controlling the PPF degradation and size of adsorbed SOR deposits, we were able to augment SOR anticancer effects, both in vitro and in vivo, due to the dual kinetic behavior of SOR@PPF. Obtained drug delivery systems with slow and fast release of SOR influenced effectively, although in a different way, the cancer cells proliferation (reflected with EC50 and ERK 1/2 phosphorylation level). The in vivo studies proved that fast-released SOR@PPF reduces the tumor size considerably, while the slow-released SOR@PPF much better prevents from lymph nodes involvement and distant metastases.
Highlights
Hepatocellular carcinoma (HCC) is one of the deadliest cancers due to its complexity, reoccurrence after surgical resection, metastasis and heterogeneity
Various multikinase inhibitors have been tested as systemic therapies of HCC, only sorafenib and lenvatinib deserve special mention as FDA-approved drugs for the treatment of advanced
We have focused on the PPF’s ability to meet the requirements for an anticancer drug delivery system
Summary
Hepatocellular carcinoma (HCC) is one of the deadliest cancers due to its complexity, reoccurrence after surgical resection, metastasis and heterogeneity. New cases are diagnosed annually in over 500,000 patients worldwide, and it is the second leading cause of cancer death in the world [1]. Hepatic cancer therapies are currently limited to surgery, radiation, and chemotherapy, but all these methods risk damage to normal tissues or incomplete eradication of the cancer. There is a constant search for more and more effective therapies that require even more complex, advanced drugs, consisting of active compounds and tailored drug delivery systems (DDS). Various multikinase inhibitors have been tested as systemic therapies of HCC, only sorafenib and lenvatinib (orally active multi-targeted tyrosine kinase inhibitors) deserve special mention as FDA-approved drugs for the treatment of advanced
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