Triple-negative breast cancer (TNBC) is highly recurring and metastatic breast cancer with overexpressing epidermal growth factor receptor (EGFR). Herein, a series of in vitro and in vivo analyses were used to explore the therapeutic effect of EGFR-targeting nano-micelles (PLGA-PEG/DOX@anti-EGFR) combined with ultrasound-mediated cavitation (UMC). The prepared nano-micelle drug carriers have good biocompatibility and can greatly increase the drug accumulation in tumor regions, thereby reducing off-target toxicity while enhancing anti-tumor efficacy. Moreover, an in vivo analysis of the practical utility of this treatment modality was conducted by using SonoVueTM microbubbles to achieve cavitation under different power intensity levels, with an ultrasonic power intensity of 0.5 W/cm2 maximizing the intra-tumoral blood perfusion. Relative to PLGA-PEG@DOX/anti-EGFR nano-micelles treatment alone, the combination with UMC was better able to suppress tumor growth even at low concentrations. As such, combining actively targeted drug-carrier molecules with UMC represents an effective approach to enhancing therapeutic efficacy while reducing the adverse, systemic effects associated with DOX and other chemotherapeutic drugs, and it can be considered as a promising clinical prospect in the treatment of TNBC.
Chemodynamic therapy (CDT) strategies rely on the generation
of
reactive oxygen species (ROS) to kill tumor cells, with hydroxyl radicals
(•OH) serving as the key mediators of cytotoxicity
in this setting. However, the efficacy of CDT approaches is often
hampered by the properties of the tumor microenvironment (TME) and
associated limitations to the Fenton reaction that constrains ROS
generation. As such, there is a pressing need for the design of new
nanoplatforms capable of improving CDT outcomes. In this study, an
Fc-based metal–organic framework (MOF) vitamin k3 (Vk3)-loaded
cascade catalytic nanoplatform (Vk3@Co-Fc) was developed. This platform
was capable of undergoing TME-responsive degradation without impacting
normal cells. After its release, Vk3 was processed by nicotinamide
adenine dinucleotide hydrogen phosphate (NAD(P)H) quinone oxidoreductase-1
(NQO1), which is highly expressed in tumor cells, thereby yielding
large quantities of H2O2 that in turn interact
with Fe ions via the Fenton reaction to facilitate in situ cytotoxic •OH production. This process leads to
immunogenic cell death (ICD) of the tumor, which then promotes dendritic
cell maturation and ultimately increases T cell infiltration into
the tumor site. When this nanoplatform was combined with programmed
death 1 (PD-1) checkpoint blockade approaches, it was sufficient to
enhance tumor-associated immune responses in breast cancer as evidenced
by increases in the frequencies of CD45+ leukocytes and
CD8+ cytotoxic T lymphocytes, thereby inhibiting tumor
metastasis to the lungs and improving murine survival outcomes. Together,
this Vk3@Co-Fc cascading catalytic nanoplatform enables potent cancer
immunotherapy for breast cancer regression and metastasis prevention.
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