The defeat of cancer is still a challenge due to the
existence
of cancer stem cells (CSCs) because they resist conventional chemotherapy
via multifactor regulated mechanisms. Consequently, one-dimensional
action toward CSCs cannot work. Herein, we used rationally designed
hybrid nanoparticles as a combined cancer therapy, hoping to form
a multidimensional control network. In this paper, gold/silver alloy
nanoparticle decorated camptothecin nanocrystals were formulated according
to complementary anti-CSC mechanisms from gold, silver, and organic
drug. This smart drug formulation could combine chemotherapy and thermotherapy,
target different tumor sites, and demonstrate versatile toxicity profiles
from each component. Major results indicated that this nanosystem
demonstrated indiscriminately effective cytotoxic/proapoptotic/necrotic
activity against bulk MCF-7 cells and their CSC subpopulation, in
particular under laser ablation. Moreover, this nanosystem displayed
enhanced antineoplastic activity against CSC spheroids, resulting
in a significant reduction in their number and size, that is, their
self-renewal capacity. All the results indicated that CSCs upon treatment
of these new hybrid nanoparticles underwent reduced stemness and conversion
from the original quiescent state and recovered their sensitivity
toward chemotherapy. The relevant anticancer mechanism was ascribed
to NIR-pH dual responsive drug release, synergistic/combined thermo-chemotherapy
of organic drug and inorganic alloy nanoparticles, enhanced cellular
uptake mediated by alloy nanoparticles, and Ag+-induced
biomembrane damage. This thermo-chemotherapy platform provides a new
combinatorial strategy for inorganic and organic agents in the complete
elimination of CSCs.