Quercetin (QT) is one promising candidate for the treatment of various cancers with virtually no toxic side effects. However, its anticancer effect is severely restricted by its poor bioavailability, low water solubility, and chemical instability in the neutral and alkaline medium. Herein, zeolitic imidazolate framework-8 (ZIF-8) is first reported as the multifunctional nanoplatform to the codelivery of quercetin as an anticancer agent and CuS nanoparticles as a photothermal therapy (PTT) agent for synergistic combination of chemotherapy and PTT as well as overcoming the drawbacks of quercetin. Moreover, folic acid-bovine serum albumin (FA-BSA) conjugates are applied to stabilize the CuS@ZIF-8-QT to promote the bioavailability of quercetin and realize active-targeting drug delivery. Near-infrared (NIR) fluorescent imaging demonstrated the highly increased drug accumulations of FA-BSA/CuS@ZIF-8-QT in tumors, resulting from efficient internalization via FA-receptors-mediated endocytosis. The results of in vivo and in vitro anticancer experiments demonstrate that quercetin and PTT agent can work together efficiently under NIR irradiation, thus remarkably improving the anticancer effect. Therefore, our newly designed FA-BSA/CuS@ZIF-8-QT multifunctional drug delivery system might be a promising nanoplatform for cancer treatment.

Increasing numbers of disulfide linkage-employing polymeric drug carriers that utilize the reversible peculiarity of this unique covalent bond have been reported. The reduction-sensitive disulfide bond is usually employed as a linkage between hydrophilic and hydrophobic polymers, polymers and drugs, or as cross-linkers in polymeric drug carriers. These polymeric drug carriers are designed to exploit the significant redox potential difference between the reducing intracellular environments and relatively oxidizing extracellular spaces. In addition, these drug carriers can release a considerable amount of anticancer drug in response to the reducing environment when they reach tumor tissues, effectively improving antitumor efficacy. This review focuses on various disulfide linkage-employing polymeric drug carriers. Important redox thiol pools, including GSH/GSSG, Cys/CySS, and Trx1, as well as redox environments in mammals, will be introduced.

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