The assemblies of anisotropic nanomaterials
have attracted considerable
interest in advanced tumor therapeutics because of the extended surfaces
for loading of active molecules and the extraordinary responses to
external stimuli for combinatorial therapies. These nanomaterials
were usually constructed through templated or seed-mediated hydrothermal
reactions, but the lack of uniformity in size and morphology, as well
as the process complexities from multiple separation and purification
steps, impede their practical use in cancer nanotherapy. Gas-phase
epitaxy, also called aerotaxy (AT), has been introduced as an innovative
method for the continuous assembly of anisotropic nanomaterials with
a uniform distribution. This process does not require expensive crystal
substrates and high vacuum conditions. Nevertheless, AT has been used
limitedly to build high-aspect-ratio semiconductor nanomaterials.
With these considerations, a modified AT was designed for the continuous
in-flight assembly of the cell-penetrating Fenton nanoagents (Mn–Fe
CaCO3 (AT) and Mn–Fe SiO2 (AT)) in a
single-pass gas flow because cellular internalization activity is
essential for cancer nanotherapeutics. The modified AT of Mn–Fe
CaCO3 and Mn–Fe SiO2 to generate surface
nanoroughness significantly enhanced the cellular internalization
capability because of the preferential contact mode with the cancer
cell membrane for Fenton reaction-induced apoptosis. In addition,
it was even workable for doxorubicin (DOX)-resistant cancer cells
after DOX loading on the nanoagents. After combining with immune-checkpoint
blockers (antiprogrammed death-ligand 1 antibodies), the antitumor
effect was improved further with no systemic toxicity as chemo-immuno-chemodynamic
combination therapeutics despite the absence of targeting ligands
and external stimuli.