Nanoformulation-based sequential combination cancer therapy

Although combining two or more treatments is regarded as an indispensable approach for effectively treating cancer, the traditional cocktail-based combination therapies are seriously limited by coordination issues that fail to account for differences in the pharmacokinetics and action sites of each drug. The careful manipulation of dosing regimens, such as by the sequential application of combination treatments, may satisfy the temporal and spatial needs of each drug and achieve successful combination antitumor therapy. Nanotechnology-based carriers might be the best tools for sequential combination therapy, as they can be loaded with multiple cargos and may provide targeted and sustained delivery to target tumor cells. Single nanoformulations capable of sequentially releasing drugs have shown synergistic anticancer activity, such as by sensitizing tumor cells through cascaded drug delivery or remodeling the tumor vasculature and microenvironment to enhance the tumor distribution of nanotherapeutics. This review highlights the use of nanotechnology-based multistage drug delivery for cancer treatment, focusing on the ability of such formulations to enhance antitumor efficacy by applying sequential treatment and modulating dosing regimens, which are challenges currently being faced in the clinic.