Recent Advances in Strategies for Addressing Hypoxia in Tumor Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) is a treatment modality that uses light to target tumors and minimize damage to normal tissues. It offers advantages including high spatiotemporal selectivity, low side effects, and maximal preservation of tissue functions. However, the PDT efficiency is severely impeded by the hypoxic feature of tumors. Moreover, hypoxia may promote tumor metastasis and tumor resistance to multiple therapies. Therefore, addressing tumor hypoxia to improve PDT efficacy has been the focus of antitumor treatment, and research on this theme is continuously emerging. In this review, we summarize state-of-the-art advances in strategies for overcoming hypoxia in tumor PDTs, categorizing them into oxygen-independent phototherapy, oxygen-economizing PDT, and oxygen-supplementing PDT. Moreover, we highlight strategies possessing intriguing advantages such as exceedingly high PDT efficiency and high novelty, analyze the strengths and shortcomings of different methods, and envision the opportunities and challenges for future research.

Aggregation-Induced Emission Luminogens for Enhanced Photodynamic Therapy: From Organelle Targeting to Tumor Targeting

“…Although the emergence of AIE strategies has solved the problem of poor efficacy of PDT in vivo to a certain extent, PDT still faces many problems at present [ 36 , 189 ]. However, the main challenges of PDT are not only limited to light intensity in tissues, tumor hypoxia, and low accumulation efficiency of PSs in tumors [ 190 , 191 , 192 ]. Future efforts should be devoted to the following aspects: (1) Developing AIE-based PSs targeting the less-reported organelles, such as the GA or nucleus, is worthy of investigation; (2) developing novel nanoparticle carries and targeting conjugates to modify AIE-PSs and improve their water solubility, tumor targeting and delivery efficiency [ 193 ]; (3) developing AIEgen-based PSs with NIR I or NIR II absorption and Type I PDT abilities to overcome the limited penetration depth and the drug resistance of tumors under hypoxia; (4) the construction of AIE-PSs with both tumor-targeting and organelle-targeting abilities to optimize the therapeutic performance; (5) smart AIEgen-based PSs which show stimuli-responsive abilities and combined therapeutic effects such as PDT, PTT, immunotherapy and sonodynamic therapy [ 193 ] are also highly desirable; (6) some tumor cells are resistant to one certain cell death mode, and therefore developing AIE-PSs that can cause multiple cell death pathways are appealing for the effective inhibition of these tumor cells.…”

Boosting Type-I and Type-II ROS Production of Water-Soluble Porphyrin for Efficient Hypoxic Tumor Therapy

“…Photodynamic therapy (PDT) has attracted great attention in curing cancers due to its minimal invasiveness and side effects, spatiotemporal selectivity, and high therapeutic efficacy compared to conventional cancer treatments. − In PDT, the photoexcited photosensitizers (PSs) convert triplet oxygen and other molecules into cytotoxic reactive oxygen species (ROS) via electron transfer (type-I) or energy transfer (type-II), which subsequently induce apoptosis or necrosis of tumor cells. − However, the high hydrophobicity-caused aggregation of PSs under physiological conditions usually results in significant self-quenching of excitons, thereby decreasing their ROS generation efficacy severely. ,, Additionally, the hypoxic microenvironment of solid tumors further hinders most type-II PSs from achieving satisfactory in vivo PDT performance. ,,− …”

Light-responsive nanodrugs co-self-assembled from a PEG-Pt(iv) prodrug and doxorubicin for reversing multidrug resistance in the chemotherapy process of hypoxic solid tumors

“…15,16 However, the presence of hypoxia would significantly reduce the efficacy of chemotherapy and PDT treatment. [17][18][19][20] Therefore, it has received much attention on how to alleviate hypoxia and reverse MDR to enhance the efficacy of chemotherapy in solid tumors.…”