Synthesis of 5-Fu/ICG@ZIF-90-PEG-ZOL. Design based on bone-targeted modification on the surface of nanocarrier with ZOL, and also in combination chemotherapy and photothermal therapy (created in BioRender.com).

Traditional chemotherapy remains the primary cancer treatment, but it shows low enrichment and non-specificity. Hence, we have designed a multifunctional nanocarrier based on glutathione (GSH)-responsive mesoporous silica nanoparticles (MSNs). Firstly, disulfide bonds were linked on the surface of mesoporous silica. Then, doxorubicin (DOX) and chlorin e6 (Ce6) were co-loaded into the pores. Finally, carboxymethyl chitosan (CMCS) coated the nanoparticles to obtain the DOX/Ce6@MSN-SS-CMCS (DOX/Ce6@MSC) nanocarrier. The synthesized DOX/Ce6@MSC showed good monodispersity, dimensional stability, and consistent spectral characteristics. DOX/Ce6@MSC could effectively enter cancer cells and successfully deliver drugs. Under 660 nm laser irradiation, DOX/Ce6@MSC exhibited an effective photodynamic therapy effect that resists MCF-7 cells by triggering reactive oxygen species production. Thereby, it could efficiently inhibit cell proliferation and induce cell death. Anticancer analysis of tumor-bearing mice demonstrates that the DOX/Ce6@MSC combination treatment induced cell apoptosis effectively and showed an excellent antitumor effect in vivo. Therefore, DOX/Ce6@MSC nano-drug delivery system could be an effective strategy in cancer treatment.

Recently, the combination of chemotherapy and chemodynamic therapy (CDT) has become a desirable strategy in the treatment of cancer. However, a satisfactory therapeutic outcome is often difficult to achieve due to the deficiency of endogenous H2O2 and O2 in the tumor microenvironment. In this study, a CaO2@DOX@Cu/ZIF-8 nanocomposite was prepared as a novel nanocatalytic platform to enable the combination of chemotherapy and CDT in cancer cells. The anticancer drug doxorubicin hydrochloride (DOX) was loaded onto calcium peroxide (CaO2) nanoparticles (NPs) to form CaO2@DOX, which was then encapsulated in a copper zeolitic imidazole ester MOF (Cu/ZIF-8) to form CaO2@DOX@Cu/ZIF-8 NPs. In the mildly acidic tumor microenvironment, CaO2@DOX@Cu/ZIF-8 NPs rapidly disintegrated, releasing CaO2, which reacted with water to generate H2O2 and O2 in the tumor microenvironment. The ability of CaO2@DOX@Cu/ZIF-8 NPs to combine chemotherapy and CDT was assessed by conducting cytotoxicity, living dead staining, cellular uptakes, H&E staining, and TUNEL assays in vitro and in vivo. The combination of chemotherapy and CDT of CaO2@DOX@Cu/ZIF-8 NPs had a more favorable tumor suppression effect than the nanomaterial precursors, which were not capable of the combined chemotherapy/CDT.

Photothermal therapy has been widely used in the treatment of bacterial infections. However, the short photothermal effective radius of conventional nano-photothermal agents makes it difficult to achieve effective photothermal antibacterial activity. Therefore, improving composite targeting can significantly inhibit bacterial growth. We inhibited the growth of Staphylococcus aureus (S. aureus) by using an extremely low concentration of vancomycin (Van) and applied photothermal therapy with molybdenum disulfide (MoS2). This simple method used chitosan (CS) to synthesize fluorescein 5(6)-isothiocyanate (FITC)-labeled and Van-loaded MoS2-nanosheet hydrogels (MoS2-Van-FITC@CS). After modifying the surface, an extremely low concentration of Van could inhibit bacterial growth by trapping bacteria synergistically with the photothermal effects of MoS2, while FITC labeled bacteria and chitosan hydrogels promoted wound healing. The results showed that MoS2-Van-FITC@CS nanosheets had a thickness of approximately 30 nm, indicating the successful synthesis of the nanosheets. The vitro antibacterial results showed that MoS2-Van-FITC with near-infrared irradiation significantly inhibited S. aureus growth, reaching an inhibition rate of 94.5% at nanoparticle concentrations of up to 100 µg/mL. Furthermore, MoS2-Van-FITC@CS could exert a healing effect on wounds in mice. Our results demonstrate that MoS2-Van-FITC@CS is biocompatible and can be used as a wound-healing agent.

Chemodynamic therapy (CDT) is a highly promising tumor treatment modality that uses the Fenton reaction to convert intracellular hydrogen peroxide (H2O2) into cytotoxic hydroxyl groups (•OH). However, the therapeutic effects of CDT have been restricted by weak acidic pH values, insufficient H2O2 levels, and high glutathione (GSH) concentrations in the tumor microenvironment (TME). In this study, to construct PCN-224-Pt/GOD, porphyrin-based metal–organic framework nanoparticles (PCN-224) were used as the carrier to load Pt and glucose oxidase (GOD). The surface of PCN-224-Pt/GOD was covered with manganese dioxide (MnO2) to fabricate the multifunctional composite nanoparticles PCN-224-Pt/GOD@MnO2 (P–P/GOD@Mn). P–P/GOD@Mn was used to increase H2O2 levels and to decrease GSH levels for combined CDT and starvation therapy. As a result, we developed P–P/GOD@Mn nanoparticles (diameter, approximately 280 nm) with favorable size and biocompatibility. Under simulated TME conditions, P–P/GOD@Mn nanoparticles could catalyze H2O2 to generate cytotoxic hydroxyl radicals (•OH), consume glutathione (GSH), and decompose H2O2 to generate oxygen (O2). Cellular toxicity assay results showed that P–P/GOD@Mn killed MCF-7 cells in the TME, with a rate of 77%. The results of tumor-bearing mouse experiments proved that P–P/GOD@Mn nanoparticles could significantly suppress tumor cell growth, which shows the great potential of this entity in CDT and its possibility in bimodal cancer therapy.