Background: Sonodynamic therapy (SDT) and its synergistic cancer therapy derivatives, such as combined chemotherapy-SDT (chemo-SDT), are promising approaches for tumor treatment. However, the main drawbacks restricting their applications are hypoxia in tumors and the reducing microenvironment or high glutathione (GSH) levels. Methods: In this study, a hybrid metal MnO2 was deposited onto nanoparticles fabricated using poly(lactic-co-glycolic acid) (PLGA), carrying docetaxel (DTX) and the sonosensitizer hematoporphyrin monomethyl ether (HMME) ([email protected]2) via a one-step flash nanoprecipitation (FNP) method. Characterization and in vitro and in vivo experiments were conducted to explore the chemo-SDT effect of [email protected]2 and evaluate the synergetic antitumor treatment of this nanosystem. Results: When low-power ultrasound is applied, the acquired [email protected]2, whether in solution or in MCF-7 cells, generated ROS more efficiently than other groups without MnO2 or those treated via monotherapy. Specifically, GSH-depletion was observed when MnO2 was introduced into the system. [email protected]2 presented good biocompatibility and biosafety in vitro and in vivo. These results indicated that the [email protected]2 nanoparticles overcame hypoxia in tumor tissue and suppressed the expression of hypoxia-inducible factor 1 alpha (HIF-1α), achieving enhanced chemo-SDT. Conclusion: This study provides a paradigm that rationally engineered multifunctional metal-hybrid nanoparticles can serve as an effective platform for augmenting the antitumor therapeutic efficiency of chemo-SDT.
Artemisinin has an endoperoxide bridge structure, which can be cleaved by ferrous ions to generate various carbonyl radicals in an oxygen-independent manner, highlighting its potential for treating hypoxic tumors. In our study, we fabricated Tween 80 micelles loaded with Fe3O4 nanoparticles and artemisinin for cancer therapy. The synthesized Fe3O4 nanoparticles and drug-loaded micelles have particle sizes of about 5 nm and 80 nm, respectively, both exhibiting excellent dispersibility and stability. After uptake by MCF-7 cells, drug-loaded micelles release Fe2+ and ART into the cytoplasm, effectively inducing the generation of reactive oxygen species (ROS) in hypoxic conditions, thereby enhancing toxicity against cancer cells. In vitro and in vivo studies have demonstrated that ART and Fe3O4 nanoparticles are encapsulated in Tween 80 to form micelles, which effectively prevent premature release during circulation in the body. Although free ART and Fe3O4 nanoparticles can inhibit tumor growth, TW80-Fe3O4-ART micelles demonstrate a more pronounced inhibitory effect, with a tumor suppression rate of up to 85%. A novel strategy based on artemisinin and ferroptosis is thus offered, holding a favorable prospect for hypoxic cancer therapy.
Background: UV radiation (UV) exposure risks skin damage and cancer due to DNA damage and oxidative stress. Synthetic chemical sunscreens that protect against UV radiation can have health and environmental concerns. This study explores phycocyanin (PC), a marine algae-derived natural photoprotective compound, and its crosslinked nanoparticles (PCNP) as safe and effective adjuvants for sunscreen systems. Methods: PCNP was synthesized via genipin-crosslinking. PC and PCNP biocompatibility were assessed on mouse embryonic fibroblast cells. ABTS evaluated antioxidant activity, and the UV absorption capacity of PC and PCNP were analyzed. PCNP skin permeability was tested in vitro and in vivo. Gel formulations with PCNP were examined for UV absorption effects. Results: PCNP showed good biocompatibility, maintaining cell viability above 90% across concentrations. Both PC and PCNP demonstrated concentration-dependent antioxidant activity, efficiently scavenging free radicals. PCNP exhibited enhanced UV absorption in the UVB range compared to PC alone. Skin permeation studies displayed limited PCNP penetration through skin layers. In vivo, absorption assessments indicated PCNP localized mainly in the stratum corneum. PCNP-containing gels displayed improved UV absorption compared to gels without PCNP. Conclusion: This study showcases PCNP’s potential as a natural and safe adjuvant for sunscreen with enhanced UV protection capabilities. PCNP preserved antioxidant activity, displayed limited skin penetration, and enhanced UV absorption. The findings suggest PCNP’s promise as a viable alternative to synthetic sunscreen agents, delivering effective photoprotection while minimizing health and environmental concerns.