Recent Progress in Reactive Oxygen Species-Related Therapy for Disease Treatment

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 8073

Special Issue Editor

School of Science, Harbin Institute of Technology, Shenzhen 518055, China
Interests: polymer chemistry; molecular imaging probes; nanomedicines; prodrugs; aggregation-induced emission; fluorescence imaging; photoacoustic imaging; microscopy; wide-field imaging; two photon imaging; second harmonic imaging
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Special Issue Information

Dear Colleagues,

Reactive oxygen species (ROS)-related therapy has attracted increasing attention in the last decade. It has advantages in high efficacy and negligible multiple drug resistance and holds great promise to be the next generation of treatment paradigms for cancers and even bacterial infections. The therapeutic ROS can be generated by sensitizers under a variety of stimuli, including light, ultrasound, X-rays, microwaves, chemical reactions, hyperthermia, and electric current. Among these ROS-related therapies with different stimuli, each has its advantages and disadvantages. Achieving optimal therapeutic treatment outcomes requires a customized design of medicine systems specifically for the target diseases. In addition, the combinatory of ROS-related therapy with other therapies such as chemotherapy, photothermal therapy, and radiotherapy would synergistically boost the treatment efficacy.

In this Special Issue, we systematically update the latest research progress on ROS-related therapy and its combinatory therapy. The special focus is on the state-of-the-art of medicine design, formulation technology, and their applications in the therapy of tumors and bacterial infection. This issue is a valuable platform for interested researchers to actively participate in the discussion. We accept original research articles, critical review papers, and commentaries to stimulate the further development of ROS-related therapy for disease treatment.

Research areas may include, but are not limited to, the following:

  • Photodynamic therapy
  • Sonodynamic therapy
  • X-ray dynamic therapy
  • Chemodynamic therapy
  • Electric-dynamic therapy
  • Hyperthermia induced dynamic therapy
  • Nanomedicines
  • Imaging-guided therapy
  • Combinatory Therapy
  • Therapy of cancers and bacterial infection
  • Targeted Therapy

We look forward to receiving your contributions.

Dr. Bing Guo
Guest Editor

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Published Papers (5 papers)

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Research

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15 pages, 3770 KiB  
Article
A NIR-Activated and Mild-Temperature-Sensitive Nanoplatform with an HSP90 Inhibitor for Combinatory Chemotherapy and Mild Photothermal Therapy in Cancel Cells
by Yingying Peng, Hanlin Jiang, Bifei Li, Yue Liu, Bing Guo and Wei Gan
Pharmaceutics 2023, 15(9), 2252; https://doi.org/10.3390/pharmaceutics15092252 - 31 Aug 2023
Cited by 2 | Viewed by 999
Abstract
Mild photothermal therapy (PTT) shows great potential to treat cancers while avoiding unwanted damage to surrounding normal cells. However, the efficacy of mild PTT is normally moderate because of the low hyperthermia temperature and limited light penetration depth. Chemotherapy has unlimited penetration but [...] Read more.
Mild photothermal therapy (PTT) shows great potential to treat cancers while avoiding unwanted damage to surrounding normal cells. However, the efficacy of mild PTT is normally moderate because of the low hyperthermia temperature and limited light penetration depth. Chemotherapy has unlimited penetration but often suffers from unsatisfactory efficacy in view of the occurrence of drug resistance, suboptimal drug delivery and release profile. As a result, the combinatory of chemotherapy and mild PTT would integrate their advantages and overcome the shortcomings. Herein, we synthesized an NIR-activatable and mild-temperature-sensitive nanoplatform (BDPII-gel@TSL) composed of temperature-sensitive liposomes (TSL), heat shock protein 90 (HSP90) inhibitor (geldanamycin) and photothermal agent (BDPII), for dual chemotherapy and mild PTT in cancer cells. BDPII, constructed with donor-acceptor moieties, acts as an excellent near-infrared (NIR) photothermal agent (PTA) with a high photothermal conversion efficiency (80.75%). BDPII-containing TSLs efficiently produce a mild hyperthermia effect (42 °C) under laser irradiation (808 nm, 0.5 W cm−2). Importantly, the phase transformation of TSL leads to burst release of geldanamycin from BDPII-gel@TSL, and this contributes to down-regulation of the overexpression of HSP90, ensuring efficient inhibition of cancer cell growth. This research provides a dual-sensitive synergistic therapeutic strategy for cancer cell treatment. Full article
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15 pages, 5784 KiB  
Article
Cascade Amplification of Pyroptosis and Apoptosis for Cancer Therapy through a Black Phosphorous-Doped Thermosensitive Hydrogel
by Qing Wu, Qinghui Ma, Jun Ma, Junpeng Chen, Baoding Zhuang, Shanglin Yang, Jinji Liu and Shunqian Wen
Pharmaceutics 2023, 15(7), 1830; https://doi.org/10.3390/pharmaceutics15071830 - 26 Jun 2023
Cited by 1 | Viewed by 1308
Abstract
Cell pyroptosis has a reciprocal relationship with various cancer treatment modalities such as chemotherapy. However, the tumor microenvironment, characterized by hypoxia, substantially restricts the development and application of tumor therapies that integrate cell pyroptosis. Therefore, the cascade amplification of oxidative stress by interfering [...] Read more.
Cell pyroptosis has a reciprocal relationship with various cancer treatment modalities such as chemotherapy. However, the tumor microenvironment, characterized by hypoxia, substantially restricts the development and application of tumor therapies that integrate cell pyroptosis. Therefore, the cascade amplification of oxidative stress by interfering with redox homeostasis in tumors may be a promising approach. In this study, black phosphorus (BP) nanosheets and a glutathione peroxidase 4 inhibitor (RSL3) were coloaded into a thermosensitive PDLLA-PEG-PDLLA (PLEL) hydrogel (RSL3/BP@PLEL). Owing to the photothermal property of BP nanosheets, the RSL3/BP@PLEL hydrogel may trigger the release of loaded drugs in a more controllable and on-demand manner. Investigation of the antitumor effect in a mouse liver tumor model demonstrated that local injection of the hydrogel formulation in combination with near infrared laser irradiation could efficiently suppress tumor growth by interfering with the redox balance in tumors. Mechanistic study indicated that the combined treatment of photothermal therapy and glutathione depletion based on this hydrogel efficiently induced cell pyroptosis through both caspase-1/GSDMD and caspase-3/GSDME pathways, thereby triggering the repolarization of tumor-associated macrophages from M2 to M1. Overall, we developed a biocompatible and biodegradable hydrogel formulation for application in combination cancer treatment, providing a new platform for enhancing the efficacy of cancer therapy by amplifying cell pyroptosis and apoptosis. Full article
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21 pages, 4467 KiB  
Article
A Novel Fibromodulin Antagonist Peptide RP4 Exerts Antitumor Effects on Colorectal Cancer
by Ting Deng, Yibo Hou, Gaoyang Lin, Chunyan Feng, Kewei Liu, Wenke Chen, Wei Wei, Laiqiang Huang and Xiaoyong Dai
Pharmaceutics 2023, 15(3), 944; https://doi.org/10.3390/pharmaceutics15030944 - 14 Mar 2023
Cited by 3 | Viewed by 1732
Abstract
Colorectal cancer (CRC) is the leading cause of cancer-related deaths worldwide. Fibromodulin (FMOD) is the main proteoglycan that contributes to extracellular matrix (ECM) remodeling by binding to matrix molecules, thereby playing an essential role in tumor growth and metastasis. There are still no [...] Read more.
Colorectal cancer (CRC) is the leading cause of cancer-related deaths worldwide. Fibromodulin (FMOD) is the main proteoglycan that contributes to extracellular matrix (ECM) remodeling by binding to matrix molecules, thereby playing an essential role in tumor growth and metastasis. There are still no useful drugs that target FMOD for CRC treatment in clinics. Here, we first used public whole-genome expression datasets to analyze the expression level of FMOD in CRC and found that FMOD was upregulated in CRC and associated with poor patient prognosis. We then used the Ph.D.-12 phage display peptide library to obtain a novel FMOD antagonist peptide, named RP4, and tested its anti-cancer effects of RP4 in vitro and in vivo. These results showed that RP4 inhibited CRC cell growth and metastasis, and promoted apoptosis both in vitro and in vivo by binding to FMOD. In addition, RP4 treatment affected the CRC-associated immune microenvironment in a tumor model by promoting cytotoxic CD8+ T and NKT (natural killer T) cells and inhibiting CD25+ Foxp3+ Treg cells. Mechanistically, RP4 exerted anti-tumor effects by blocking the Akt and Wnt/β-catenin signaling pathways. This study implies that FMOD is a potential target for CRC treatment, and the novel FMOD antagonist peptide RP4 can be developed as a clinical drug for CRC treatment. Full article
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12 pages, 3193 KiB  
Article
LL-37-Coupled Porous Composite Scaffold for the Treatment of Infected Segmental Bone Defect
by Xialin Li, Xingyu Huang, Long Li, Jiayi Wu, Weihong Yi, Yuxiao Lai and Lei Qin
Pharmaceutics 2023, 15(1), 88; https://doi.org/10.3390/pharmaceutics15010088 - 27 Dec 2022
Cited by 3 | Viewed by 1633
Abstract
Increased multiantibiotic-resistant bacteria means that infected bone defects remain a significant challenge to clinics. Great interest has emerged in the use of non-antibiotic antimicrobials to reduce the rate of multiantibiotic-resistant bacterial infection and facilitate bone regeneration. The cationic antimicrobial peptide LL-37 is the [...] Read more.
Increased multiantibiotic-resistant bacteria means that infected bone defects remain a significant challenge to clinics. Great interest has emerged in the use of non-antibiotic antimicrobials to reduce the rate of multiantibiotic-resistant bacterial infection and facilitate bone regeneration. The cationic antimicrobial peptide LL-37 is the sole human cathelicidin and has shown nonspecific activity against a broad spectrum of microorganisms. In this study, we fabricated the poly(lactic-co-glycolic acid)/β-calcium phosphate/peptide LL-37 (PLGA/TCP/LL-37, PTL) scaffold with low-temperature 3D-printing technology for the treatment of infected segmental bone defects. The prepared scaffolds were divided into three groups: a high LL-37 concentration group (PTHL), low LL-37 concentration group (PTLL) and blank control group (PT). The cytocompatibility and antimicrobial activity of the engineered scaffolds were tested in vitro, and their osteogenesis properties were assessed in vivo in a rat infected bone defect model. We found the fabricated PTL scaffold had a well-designed porous structure that could support a steady and prolonged LL-37 release. Furthermore, the PTHL group showed strong antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) without any inhibition of the proliferation or alkaline phosphatase activity of rat bone marrow mesenchymal stem cells (BMSCs) in vitro. In addition, the infected femoral defects implanted with PTHL group displayed new bone formation in four weeks without any evidence of residual bacteria, which showed similar antibacterial outcomes to the vancomycin and cancellous bone mixture group. In conclusion, the PTHL composite scaffold is a promising non-antibiotic antimicrobial graft with good biodegradability, biocompatibility, and osteogenic capability for infected bone defects. Full article
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Review

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22 pages, 3665 KiB  
Review
Nanomaterial-Based Antivascular Therapy in the Multimodal Treatment of Cancer
by Xiaocong Ma, Weimin Fang, Duo Wang, Ni Shao, Jifeng Chen, Tianqi Nie, Cuiqing Huang, Yanyu Huang, Liangping Luo and Zeyu Xiao
Pharmaceutics 2023, 15(4), 1207; https://doi.org/10.3390/pharmaceutics15041207 - 11 Apr 2023
Cited by 2 | Viewed by 1724
Abstract
Abnormal tumor vasculature and a hypoxic tumor microenvironment (TME) limit the effectiveness of conventional cancer treatment. Recent studies have shown that antivascular strategies that focus on antagonizing the hypoxic TME and promoting vessel normalization effectively synergize to increase the antitumor efficacy of conventional [...] Read more.
Abnormal tumor vasculature and a hypoxic tumor microenvironment (TME) limit the effectiveness of conventional cancer treatment. Recent studies have shown that antivascular strategies that focus on antagonizing the hypoxic TME and promoting vessel normalization effectively synergize to increase the antitumor efficacy of conventional therapeutic regimens. By integrating multiple therapeutic agents, well-designed nanomaterials exhibit great advantages in achieving higher drug delivery efficiency and can be used as multimodal therapy with reduced systemic toxicity. In this review, strategies for the nanomaterial-based administration of antivascular therapy combined with other common tumor treatments, including immunotherapy, chemotherapy, phototherapy, radiotherapy, and interventional therapy, are summarized. In particular, the administration of intravascular therapy and other therapies with the use of versatile nanodrugs is also described. This review provides a reference for the development of multifunctional nanotheranostic platforms for effective antivascular therapy in combined anticancer treatments. Full article
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