Targeted blockage of tumor blood supply to deprive its nutrients and oxygen is very attractive strategy to combat cancers. This approach is less prone to incur drug resistance and potentially works for a broad spectrum of cancers, as long as their fast grow heavily relying on those blood vessels. Although the idea is cool and simple, in the real-world scenario, it is very challenging to develop a “smart” drug which is only targeting to cancer blood system, but not that of the other normal tissues.
To address this unmet medical challenge, in a recent study published in Nature Biomedical Engineering on June 22, Profs. Nie Guangjun, Wu Yan, Zhao Yuliang and their colleagues from National Center for Nanoscience and Technology, China, developed an intelligent nanomedicine to deliver not only clotting factor thrombin, but also a chemotherapeutic drug doxorubicin (Dox) into the tumor tissues. This strategy simultaneously delivers the first line drug Dox with thrombin and synergistically kills tumors. The combined therapeutic efficacy is significantly improved in multiple animal models. At the same time, acceptable toxicity profile associated with the combined treatment has been achieved. This study provides a novel strategy for improving the therapeutic index of coagulation-based tumor therapy for a wide range of solid tumors, where their fast growth occurs.
Harnessing the economical, biodegradable and biocompatible properties, polymeric chitosan nanoparticles were used to make the intelligent nanomedicine. To specifically target to tumor tissue, a tumor-homing pentapeptide with the sequence of Cys-Arg-Glu-Lys-Ala (CREKA) was functionalized onto the surfaces of the nanomedicine (Figure 1). Fibrin-fibronectin complexes, the targets of CREKA peptide, distribute uniquely on tumor vessel walls and in stroma, due to the tumor-associated high tendency of coagulability. The targeting signals can even be amplified when therapeutic thrombus was formed, thereby attracting more nanomedicines to accumulate in the tumor tissues. When giving that smart nanomedicine to tumor bearing animals, one can observe more tumor cells are killed — both the tumor cells in the tumor core and those located in the tumor rim, far from vascular infarction monotherapy can reach.
This work not only improves the therapeutic effect of tumor infarction, but also develops new possible approach for chemoembolization for clinical hepatocellular carcinoma therapy. In contrast to the existed chemoembolization, the use of the smart nanomedicines may avoid physical injury caused by the catheter during the drug administration process. In addition, systemic administration can be performed without the aid of specialized interventional radiologists, with easily controlled dosage. The current study opens a door to further develop nanosystem with various properties to deliver both chemotherapeutics or antibody drugs and clotting inducer for synergistic tumor therapy.
Figure 1. Design of the smart nanomedicines for combined treatment of tumor blood vessels and tumor cells