Zeolitic
imidazole frameworks (ZIFs) are becoming a notable nanosystem in biomedicine field, due to their unique properties of favorable biocompatibility, pH-responsive degradable structure and high
drug loading. Compared with the increasing attention on ZIF-8 in
cancer diagnosis and treatment, there is limited research about the bio-application of
ZIF-90, especially its in vivo therapeutic efficacy and related toxicity. Here, we synthesize nano
ZIF-90 through a fast self-assembling process, and the synthesized nano
ZIF-90 is about 75 nm with a negative zeta potential, providing better mitochondria targetability, cell biocompatibility and in vivo survival rate comparing to nano ZIF-8. To further explore the applicability of
ZIF-90 in
cancer treatment, a facile post-modification is used to conjugate Y1 receptor
ligand [Asn6, Pro34]-NPY (AP) on the surface of
doxorubicin (DOX)-encapsulated nano
ZIF-90. AP-ZIF-90 significantly reduces premature DOX release at physiological pH level, and triggers more effective and faster DOX release inside the
tumor cells with dual responsive to high
adenosine triphosphate (
ATP) and low pH condition. Combining targeted delivery and dual responsive release of DOX significantly improves the therapeutic efficacy of AP-ZIF-90@DOX in MDA-MB-231
tumor bearing mouse, and results in 80% survival rate over 40 days of treatment. At the given dosage, nano
ZIF-90 is with excellent biocompatibility in vivo, inducing minimal side effect on the liver and renal functions. Therefore, nano
ZIF-90 combines with Y1 receptor
ligand with favorable biocompatibility and dual responsiveness can be used as a promising nanosystem for targeted
triple negative breast cancer treatment in vivo.