The hallmark of tumorigenesis is the successful circumvention of cell death regulation for achieving unlimited replication and immortality. Ferroptosis is a newly identified type of cell death dependent on lipid peroxidation which differs from classical programmed cell death in terms of morphology, physiology and biochemistry. The broad spectrum of injury and tumor tolerance are the main reasons for radiotherapy and chemotherapy failure. The effective rate of tumor immunotherapy as a new treatment method is less than 30%. Ferroptosis can be seen in radiotherapy, chemotherapy, and tumor immunotherapy; therefore, ferroptosis activation may be a potential strategy to overcome the drug resistance mechanism of traditional cancer treatments. In this review, the characteristics and causes of cell death by lipid peroxidation in ferroptosis are briefly described. In addition, the three metabolic regulations of ferroptosis and its crosstalk with classical signaling pathways are summarized. Collectively, these findings suggest the vital role of ferroptosis in immunotherapy based on the interaction of ferroptosis with tumor immunotherapy, chemotherapy and radiotherapy, thus, indicating the remarkable potential of ferroptosis in cancer treatment.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cac2.12250

Ferroptosis in cancer and cancer immunotherapy

Rationale: Photothermal therapy employs the photoabsorbers to generate heat under the near-infrared (NIR) irradiation for thermal tumor ablation. However, NIR irradiation might damage the adjacent tissue due to the leakage of the photoabsorbers and the residual materials after treatment might hinder the local healing process. A bifunctional hydrogel that holds both photothermal property and potent pro-healing ability provides a viable option to resolve this issue. Methods: In this study, we developed a bioinspired green hydrogel (BVSF) with the integration of bioproduct biliverdin into natural derived silk fibroin matrix for antiglioma photothermal therapy and wound healing. Results: The BVSF hydrogel possessed excellent and controllable photothermal activity under NIR irradiation and resulted in effective tumor ablation both in vitro and in vivo. Additionally, the BVSF hydrogel exerted anti-inflammatory effects both in vitro and in vivo, and stimulated angiogenesis and wound healing in a full-thickness defect rat model. Conclusion: Overall, this proof-of-concept study was aimed to determine the feasibility and reliability of using an all-natural green formulation for photothermal therapy and post-treatment care.

Bioinspired biliverdin/silk fibroin hydrogel for antiglioma photothermal therapy and wound healing.

Abstract Osteoarthritis (OA) is a progressive chronic inflammation that leads to cartilage degeneration. OA Patients are commonly given pharmacological treatment, but the available treatments are not sufficiently effective. The development of sustained-release drug delivery systems (DDSs) for OA may be an attractive strategy to prevent rapid drug clearance and improve the half-life of a drug at the joint cavity. Such delivery systems will improve the therapeutic effects of anti-inflammatory effects in the joint cavity. Whereas, for disease-modifying OA drugs (DMOADs) which target chondrocytes or act on mesenchymal stem cells (MSCs), the cartilage-permeable DDSs are required to maximize their efficacy. This review provides an overview of joint structure in healthy and pathological conditions, introduces the advances of the sustained-release DDSs and the permeable DDSs, and discusses the rational design of the permeable DDSs for OA treatment. We hope that the ideas generated in this review will promote the development of effective OA drugs in the future.

https://www.tandfonline.com/doi/pdf/10.1080/10717544.2022.2048130?needAccess=true

Intra-articular drug delivery systems for osteoarthritis therapy: shifting from sustained release to enhancing penetration into cartilage

Therapeutic application and construction of bilirubin incorporated nanoparticles.

Regulation of cellular oxidative stress plays a critical role in revealing the molecular mechanisms of cellular activities and thus is a potential strategy for tumor treatment. Optical methods have been employed for intelligent regulation of oxidative stress in tumor regions. However, long-time continuous irradiation inevitably causes damage to normal tissues. Herein, a ferrocene-containing nucleic acid-based energy-storage nanoagent was designed to achieve the continuous photo-regulation of cellular oxidative stress in the dark. Specifically, the photoenergy stored in the agent could convert effectively and accelerate Fenton-like reaction continuously, augmenting cellular oxidative stress. This nanoagent could also silence oxidative damage repair genes to further amplify oxidative stress. This strategy not only provides oxidative stress regulation for studying the molecular mechanisms of biological activities, but also offers a promising step toward tumor microenvironment modulation.

Ferrocene-Containing Nucleic Acid-Based Energy-Storage Nanoagent for Continuously Photo-Induced Oxidative Stress Amplification.

Tumor cells usually display metabolic, genetic, and microenvironment-related alterations, which are beneficial to tumor proliferation, tumor development, and resistance occurrence. Many transporter...

Tumor Microenvironment-Responsive, Multistaged Liposome Induces Apoptosis and Ferroptosis by Amplifying Oxidative Stress for Enhanced Cancer Therapy.

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Tumor Microenvironment-Responsive, Multistaged Liposome Induces Apoptosis and Ferroptosis by Amplifying Oxidative Stress for Enhanced Cancer Therapy.