Doxorubicin

Homing (biology)

Nanoparticle

Ecology

Biology

Biomedical engineering

Materials science

Surgery

Cancer research

Drug

Immunology

Therapeutic index

Thrombin

Nanotechnology

Myocardial infarction

Internal medicine

Pharmacology

Chemotherapy

Medicine

Chemistry

Fibrin

Platelet

Pathology

Nature Biomedical Engineering

Drugs that induce thrombosis in the tumour vasculature have not resulted in long-term tumour eradication owing to tumour regrowth from tissue in the surviving rim of the tumour, where tumour cells can derive nutrients from adjacent non-tumoral blood vessels and tissues. Here, we report the performance of a combination of tumour-infarction therapy and chemotherapy, delivered via chitosan-based nanoparticles decorated with a tumour-homing peptide targeting fibrin–fibronectin complexes overexpressed on tumour-vessel walls and in tumour stroma, and encapsulating the coagulation-inducing protease thrombin and the chemotherapeutic doxorubicin. Systemic administration of the nanoparticles into mice and rabbits bearing subcutaneous or orthotopic tumours resulted in higher tumour growth suppression and decreased tumour recurrence than nanoparticles delivering only thrombin or doxorubicin, with histological and haematological analyses indicating an absence of detectable toxicity. The co-administration of a cytotoxic payload and a protease to elicit vascular infarction in tumours with biodegradable tumour-targeted nanoparticles represents a promising strategy for improving the therapeutic index of coagulation-based tumour therapy. The combination of tumour-infarction therapy and chemotherapy, delivered via nanoparticles decorated with a tumour-homing peptide and encapsulating thrombin and doxorubicin, outperforms the corresponding monotherapies in tumour-bearing mice and rabbits.

Combination of tumour-infarction therapy and chemotherapy via the co-delivery of doxorubicin and thrombin encapsulated in tumour-targeted nanoparticles