Key Takeaways & Executive Findings
- •• Nanotechnology-based oxygen regulation strategies effectively overcome tumor hypoxia, enhancing photodynamic therapy efficacy. • China leads global research output in this field, with the Chinese Academy of Sciences and Soochow University as key contributors. • Core research themes include photodynamic therapy, nanoparticles, and tumor microenvironment-responsive strategies. • Future research trends point toward combining nanotechnology-enhanced photodynamic therapy with immunotherapy.
Abstract
BACKGROUND: Photodynamic therapy, a novel tumor treatment, is limited by the hypoxic tumor microenvironment. Nanotechnology-based oxygen regulation strategies offer a novel approach to overcoming this bottleneck. OBJECTIVE: To systematically analyze the research status of nanotechnology in improving photodynamic therapy for hypoxic solid tumors using bibliometric methods, identify hotspots, and predict future directions. METHODS: Publications and reviews from 2016 to 2025 on nanotechnology for regulating tumor hypoxia and enhancing photodynamic therapy were retrieved from the Web of Science Core Collection. Excel, CiteSpace, VOSviewer, and Bibliometrix were used for visual analysis of categories, publication trends, countries, institutions, authors, co-cited references, and keywords. RESULTS AND CONCLUSION: A total of 1,879 articles were included, with 'nanoscience & nanotechnology' as the core category. From 2016 to 2022, publications increased steadily, with a slight decline in 2023 and a subsequent rise. China was the leading country, with the Chinese Academy of Sciences having the highest output, and Liu Zhuang from Soochow University being the most prolific author. The most cited paper was by Zhou ZJ et al. (2016) in Chemical Society Reviews. The field focuses on cancer treatment, particularly microenvironment-responsive optical therapeutic strategies using nanomaterials. Keywords 'Photodynamic therapy' and 'Nanoparticles' appeared most frequently. Bibliometric analysis indicates that nanotechnology offers advantages in enhancing photodynamic therapy for hypoxic tumors, with promising efficacy and safety. Future hotspots may focus on combination with immunotherapy.
1. Introduction
Photodynamic therapy (PDT) is a non-invasive tumor treatment strategy that integrates spatial and biological selectivity, gaining widespread attention in basic and clinical research for various solid tumors [1]. The core principle of PDT involves activating photosensitizers by specific wavelengths of light to generate reactive oxygen species (ROS) in the presence of molecular oxygen, thereby inducing apoptosis, necrosis, or immunogenic cell death of tumor cells through direct damage to biomolecules such as proteins, lipids, and DNA [2]. PDT offers significant advantages including strong targeting, low toxicity, and repeatability without drug resistance, making it particularly suitable for precise intervention of focal or superficial tumors [3]. Consequently, PDT is considered a promising local treatment modality after surgery, radiotherapy, chemotherapy, and immunotherapy.
Despite its clear mechanism and targeted action, the therapeutic efficacy of PDT depends on multiple factors, including the distribution specificity of photosensitizers [4], light excitation efficiency, and tissue oxygen concentration [5-6]. Among these, the hypoxic tumor microenvironment (O2 partial pressure <10 mmHg) is a critical bottleneck limiting PDT efficacy [7]. Since ROS generation is highly dependent on oxygen molecules, abnormal proliferation, high metabolism, and vascular malformations in tumors lead to impaired oxygen delivery, significantly reducing ROS levels and weakening PDT cytotoxicity [8]. Moreover, hypoxia activates hypoxia-inducible factor 1α-mediated transcriptional programs, enhancing drug resistance, angiogenesis, and immune evasion, thereby exacerbating the heterogeneity of PDT responses [9]. Therefore, effectively improving tumor oxygenation during PDT has become a central issue in this field.
In this context, nanotechnology, with its excellent designability, biocompatibility, and tumor-targeted delivery capabilities, offers new solutions to overcome the hypoxia barrier and enhance PDT efficacy [10-12]. Researchers have developed various 'oxygen-generating' or 'oxygen-delivering' nanomaterial platforms, such as manganese dioxide (MnO2) [8], palladium/platinum nanozymes [13], metal-organic frameworks, or nanoparticles carrying H2O2/catalase [14-15], which can decompose in the acidic tumor environment to release oxygen, alleviating local hypoxia and improving PDT outcomes.
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Dilida·Bahetikelede, Zhou Xin, Wang Xinyi, Zeng Zhihan, Wang Liqiong, Hu Danrong (2026). Research status and trends of nanotechnology in improving photodynamic therapy for hypoxic tumors. Chinese Journal of Tissue Engineering Research. https://doi.org/10.12307/2026.21473
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Frequently Asked Questions
What is the main challenge in photodynamic therapy for tumors?
The main challenge is the hypoxic tumor microenvironment, which limits the generation of reactive oxygen species and reduces the efficacy of photodynamic therapy.
How does nanotechnology help improve photodynamic therapy for hypoxic tumors?
Nanotechnology enables the development of oxygen-generating or oxygen-delivering nanomaterials that can release oxygen in the tumor microenvironment, thereby alleviating hypoxia and enhancing the effectiveness of photodynamic therapy.
Which country leads the research in nanotechnology-enhanced photodynamic therapy for hypoxic tumors?
China is the leading country in this research field, with the Chinese Academy of Sciences having the highest publication output.
What are the future research trends in this field?
Future research trends may focus on combining nanotechnology-enhanced photodynamic therapy with immunotherapy to achieve synergistic antitumor effects.
What methods were used in this bibliometric analysis?
The analysis used Web of Science Core Collection data and tools such as CiteSpace, VOSviewer, and Bibliometrix to visualize publication trends, countries, institutions, authors, co-cited references, and keywords.
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