Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is a potent anticancer drug with versatile biological activities, while the clinical translation of curcumin is severely limited due to its hydrophobicity, rapid elimination, and metabolism in the blood circulation. Herein, we aim to unravel the potential of curcumin as a synergistic agent with immunotherapy in the treatment of cancers. In an effort to minimize premature release and improve the systemic bioavailability, a superior blood stable and reduction sensitive curcumin micellar formulation, of which the release can be triggered by cancer cells, is rationally designed. We have synthesized a telodendrimer (mPEG-PLA-(LA)
4
) capable of forming reversible disulfide crosslinked micelles (DCMs). The curcumin loaded DCMs (Cur/DCMs) are spherical with a uniform size of 24.6 nm. The
in vitro
release profile demonstrates that curcumin releases significantly slower from DCMs than that from non-crosslinked micelles (NCMs), while the release can be accelerated with the increasing concentration of reducing agent glutathione (GSH). Intravenous administration of Cur/DCMs stably retains curcumin in the bloodstream and efficiently improves the systemic bioavailability. Furthermore, Cur/DCMs exhibit synergistic anticancer efficacy when combined with the anti-PD-1 antibody in an MC-38 colon cancer xenograft model. Our results potentiate the integration of blood stable curcumin nanoformulation and immunotherapy for cancer treatment.
In the title compound, {[Zn(C(19)H(17)N(5)O(2))(2)(H(2)O)(2)](NO(3))(2)}(n), the Zn(II) cation is located at an inversion centre within a slightly distorted octahedron, ligated by four N atoms from four N(2),N(6)-bis[(pyridin-3-yl)methyl]pyridine-2,6-dicarboxamide (L) ligands occupying a plane about the Zn(II) atom with the two water O atoms perpendicular to that. In the complex molecule, the bidentate bridging L ligands display helical R and S conformers, and link the Zn(II) cations into a one-dimensional centrosymmetric double-chain structure containing 32-membered rings. The nitrate anions reside in these rings and are involved in multiple N-H...O hydrogen-bond interactions. On excitation at 390 nm, the title compound displays a strong blue emission centred at 449 nm. Investigation of the thermal stability shows that the network structure is stable up to 420 K.
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