Xueyong Qi

Background: Natural killer (NK) cells, as part of the group I innate lymphocytes (ILCs) are essential for tumor immune surveillance. NK cells can recognize and eliminate target cells without the need for prior sensitization or restriction of major histocompatibility complexes (MHCs) and antigens. However, the limited infiltration of metastatic NK cells poses significant challenges for advancing adoptive cell immunotherapy for solid tumors. Objective: This study aimed to explore the potential of using tumor penetrating peptide (TPP) iRGD to promote the delivery of activated NK cells to deeper layers of tumor tissue. Methods: Flow cytometry was performed to evaluate the activation, inhibition, and expression of other receptors involved in cytotoxicity. High-pressure liquid chromatography (HPLC) and mass spectrometry were used to detect the purity of iRGD. 1,2-distearoyl-sn-glycero-3- phosphoethanolamine-poly(ethylene glycol)-iRGD (DSPE-PEG-iRGD) was synthesized. Surface modification of cells was performed using DSPE-PEG-iRGD. Multicellular tumor spheroids (MCTSs) were established to evaluate permeability. In addition, in order to better simulate the physiological characteristics of solid tumors in vivo, we generated 3D spheroids from HGC27 gastric cancer cell line and BXPC-3 pancreatic cancer cell line to study the anti-tumor effect of NK cells with combination iRGD in vitro. The mouse models of gastric cancer and pancreatic cancer were used. In addition, the synergistic anti-tumor effects were evaluated in vivo based on the tumor volume and body weight of mice. Results: Initially, we treated NK cells with interleukin-2 (IL-2), resulting in significant activation as indicated by upregulation of CD56. On the 15th day, the proliferation of CD3-/56+cell population in NK cell culture containing IL-2 significantly increased, and the NK cell amplification factor was greater than 300. In addition, NK cells exhibited increased cytotoxicity towards cancer cell lines. When the ratio of effect to target was 10:1, the killing rate of NK cells against BXPC-3 was 83.1%. iRGD modification enabled NK cells to penetrate MCTSs, resulting in cytotoxicity against target HGC27 and BXPC-3 cells. In addition, NK cells modified with iRGD significantly reduced tumor growth in the xenotransplantation model of gastric cancer and pancreatic cancer mice model. Conclusion: In summary, our results indicated that NK cells exhibited higher efficacy and lifespan against cancer cell lines in vitro. Furthermore, the integration of iRGD into NK cells led to improved infiltration and targeted elimination of MCTSs. Moreover, the application of iRGDmodified NK cells has shown significant anti-tumor efficacy against solid tumors in vivo. This joint strategy may significantly improve the efficacy of NK cell immunotherapy in treating various solid tumors.

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.

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.

We propose a chemokine receptor 4 (CXCR4)-targeted combination (CTC) liposomal therapy to treat carbon tetrachloride (CCl ₄ )-induced liver fibrosis. CTC lipo reverses the liver fibrosis to normalization.

The delivery of therapeutic cancer agents via nanomaterials has received significant attention. However, because of the absence of tumour targeting, tumour treatment strategies are still not satisfactory. Umbilical cord mesenchymal stem cells are inherently prone to migrate to malignant sites, enabling them to deliver antitumour drugs effectively. Therefore, it is expected to be a promising tool for tumour targeting. In this study, we constructed magnetic drug-loaded nanoparticles comprised of ferroferric oxide and doxorubicin, which were ingested by umbilical cord mesenchymal stem cells and precisely delivered to the tumour sites. Here, we physicochemically characterized the nanoparticles for the particle size, biocompatibility and cellular uptake. The umbilical cord mesenchymal stem cells migration and homing ability before and after drug loading were evaluated. The anti-cancer effect of stem cells loaded with nanoparticles was determined using MCF-7 cells. In vitro studies, the magnetic drug-loaded nanoparticles complex on tumour cells revealed that umbilical cord mesenchymal stem cells could transport magnetic drug-loaded nanoparticles to induce robust apoptosis.