In this work, a smart
hypoxia-irrelevant
free radical nanogenerator (AIPH/PDA@
CuS/ZIF-8, denoted as APCZ) was synthesized in situ via coating
copper sulphide (
CuS)-embedded zeolitic imidazolate framework-8 (ZIF-8) on the
free radical initiator 2,2'-azobis[2-(2-imidazolin-2-yl)
propane]-dihydrochloride (AIPH)-loaded
polydopamine (PDA). APCZ showed promising GSH-depleting ability and near-infrared (NIR)-II photothermal performance for combined
cancer therapy. Once internalized by 4T1 cells, the outer ZIF-8 was rapidly degraded to trigger the release of
CuS nanoparticles (NPs), which could react with local GSH and sequentially
hydrogen peroxide (H2O2) to form
hydroxyl radical (·OH) for CDT. More importantly, the
hyperthermia generated by APCZ upon 1064 nm
laser excitation not only permitted NIR-II
photothermal therapy (PTT) and promoted CDT, but also triggered the decomposition of AIPH to give toxic alkyl radical (·R) for
oxygen-independent
PDT. Besides, the PDA together with
CuS greatly decreased the GSH level and resulted in significantly enhanced
PDT/CDT in both normoxic and hypoxic conditions. The
tumors could be completely eradicated after 14 days of treatment due to the prominent
therapeutic effects of PTT/
PDT/CDT. Additionally, the feasibility of APCZ as a photoacoustic (PA) imaging
contrast agent was also demonstrated.
CONCLUSIONS: The novel APCZ could realize the cooperative amplification effect of
free radicals-based
therapies by NIR-II light excitation and GSH consumption, and act as a
contrast agent to improve PA imaging, holding tremendous potential for efficient diagnosis and treatment of deep-seated and hypoxic
tumors.