Controllable gelation of artificial extracellular matrix for altering mass transport and improving cancer therapies

Abstract

Global alterations in the metabolic network provide substances and energy to support tumor progression. To fuel these metabolic processes, extracellular matrix (ECM) plays a dominant role in supporting the mass transport and providing essential nutrients. Here, we report a fibrinogen and thrombin based coagulation system to construct an artificial ECM (aECM) for selectively cutting-off the tumor metabolic flux. Once a micro-wound is induced, a cascaded gelation of aECM can be triggered to besiege the tumor. Studies on cell behaviors and metabolomics reveal that aECM cuts off the mass transport and leads to a tumor specific starvation to inhibit tumor growth. In orthotopic and spontaneous murine tumor models, this physical barrier also hinders cancer cells from distant metastasis. The in vivo gelation provides an efficient approach to selectively alter the tumor mass transport. This strategy results in a 77% suppression of tumor growth. Most importantly, the gelation of aECM can be induced by clinical operations such as ultrasonic treatment, surgery or radiotherapy, implying this strategy is potential to be translated into a clinical combination regimen.

A review of existing strategies for designing long-acting parenteral formulations: Focus on underlying mechanisms, and future perspectives

“…Zheng et al. 140 constructed a situ -forming artificial ECM based on fibrinogen and thrombin for selectively cutting-off the tumor metabolic flux. The physical barrier can further inhibit the metastasis of tumor cells.…”

Tailoring Chemoimmunostimulant Bioscaffolds for Inhibiting Tumor Growth and Metastasis after Incomplete Microwave Ablation

“…Thus, localized therapeutic approaches should be quite attractive for cancer treatment, owing to their powerful targeted features to change the drug redistribution in vivo , compared with conventional intravenous injection. , Specially, advances in bioengineered materials provide platforms − to select an appropriate local drug delivery system that enables sustained drug release to achieve optimal therapeutic outcomes. Among them, the natural biomaterial fibrin gel, which has already been used clinically for hemostatic therapy and peripheral nerve drug delivery, − is an excellent choice and thus employed in this work. Fibrin hydrogel was obtained by mixing thrombin and fibrinogen solutions in a 1:2 volume ratio by using a double tube syringe (Figure A,B).…”

Review on the Vascularization of Organoids and Organoids-on-a-Chip

“…The chip was very similar to natural extracellular matrix (ECM) in both water content and cytokine diffusivity and can be made into vascular chips in order to simulate disease models of blood vessels. The addition of specific acellular extracellular matrix into hydrogels as bio-inks has been reported to also promote angiogenesis ( Zheng et al, 2020 ). Hydrogels with high biocompatibility are mature platforms for 3D cell culture.…”