Anticancer nanomedicines have been proven effective in
mitigating
the side effects of chemotherapeutic drugs. However, challenges remain
in augmenting their therapeutic efficacy. Nanomedicines responsive
to the pathological abnormalities in the tumor microenvironment (TME)
are expected to overcome the biological limitations of conventional
nanomedicines, enhance the therapeutic efficacies, and further reduce
the side effects. This Review aims to quantitate the various pathological
abnormalities in the TME, which may serve as unique endogenous stimuli
for the design of stimuli-responsive nanomedicines, and to provide
a broad and objective perspective on the current understanding of
stimuli-responsive nanomedicines for cancer treatment. We dissect
the typical transport process and barriers of cancer drug delivery,
highlight the key design principles of stimuli-responsive nanomedicines
designed to tackle the series of barriers in the typical drug delivery
process, and discuss the “all-into-one” and “one-for-all”
strategies for integrating the needed properties for nanomedicines.
Ultimately, we provide insight into the challenges and future perspectives
toward the clinical translation of stimuli-responsive nanomedicines.