A method of drug delivery to tumors based on rapidly biodegradable drug-loaded containers

Abstract

To mitigate side effects in systemic administration, anticancer drugs are encapuslated in nanocontainers. The nanocontainers are impermeable through normal vessel walls but can permeate and retain in the tumor, albeit their diffusive transport in the tumor interstitium towards pharmacological targets is drastically hindered by the tumor microenvironment resulting in a compromised therapeutic efficacy. We introduce a new drug delivery concept, which relies on drug container passive accumulation in the tumor vasculature followed by an hours-scale release of small-molecule payload that cross the capillary walls to the tumor interstitium and permeates the tumor parenchyma. To demonstrate this approach, a colloidal solution of geology-inspired sub-micron vaterite particles (VPs) loaded with photosensitiser drug porphyrazine was used to deliver and visualise porphyrazine biodistribution in the tumors in vivo. The tumor uptake of polyethylene-glycol-coated gold nanorods and porphyrazine was enhanced c.a 4-fold and 1.8-fold, respectively, when formulated in VP containers. The tumor uptake of ∼30%ID/g much higher than the field average was achieved and enabled successful photodynamic therapy.