Metal- and metal-oxide-based nanoparticles have been widely exploited in cancer photodynamic therapy (PDT). Among these materials, cerium-based nanoparticles have drawn extensive attention due to their superior biosafety and distinctive physicochemical properties, especially the reversible transition between the valence states of Ce(III) and Ce(IV). In this review, the recent advances in the use of cerium-based nanoparticles as novel photosensitizers for cancer PDT are discussed, and the activation mechanisms for electron transfer to generate singlet oxygen are presented. In addition, the types of cerium-based nanoparticles used for PDT of cancer are summarized. Finally, the challenges and prospects of clinical translations of cerium-based nanoparticles are briefly addressed.Metal- and metal-oxide-based nanoparticles have been widely exploited in cancer photodynamic therapy (PDT). Among these materials, cerium-based nanoparticles have drawn extensive attention due to their superior biosafety and distinctive physicochemical properties, especially the reversible transition between the valence states of Ce(III) and Ce(IV). In this review, the recent advances in the use of cerium-based nanoparticles as novel photosensitizers for cancer PDT are discussed, and the activation mechanisms for electron transfer to generate singlet oxygen are presented. In addition, the types of cerium-based nanoparticles used for PDT of cancer are summarized. Finally, the challenges and prospects of clinical translations of cerium-based nanoparticles are briefly addressed.

Photodynamic therapy (PDT) is a new and rapidly developing treatment modality for clinical cancer therapy. Semiconductor polymer dots (Pdots) doped with photosensitizers have been successfully applied to PDT, and have made progress in the field of tumor therapy. However, the problems of severe photosensitivity and limited tissue penetration depth are needed to be solved during the implementation process of PDT. Here we developed the Pdots doped with photosensitizer molecule Chlorin e6 (Ce6) and photochromic molecule 1,2-bis(2,4-dimethyl-5-phenyl-3-thiophene)-3,3,4,5-hexafluoro-1-cyclopentene (BTE) to construct a photoswitchable nanoplatform for PDT. The Ce6-BTE-doped Pdots were in the green region, and the tissue penetration depth was increased compared with most Pdots in the blue region. The reversible conversion of BTE under different light irradiation was utilized to regulate the photodynamic effect and solve the problem of photosensitivity. The prepared Ce6-BTE-doped Pdots had small size, excellent optical property, efficient ROS generation and good photoswitchable ability. The cellular uptake, cytotoxicity, and photodynamic effect of the Pdots were detected in human colon tumor cells. The experiments in vitro indicated that Ce6-BTE-doped Pdots could exert excellent photodynamic effect in ON state and reduce photosensitivity in OFF state. These results demonstrated that this nanoplatform holds the potential to be used in clinical PDT.Photodynamic therapy (PDT) is a new and rapidly developing treatment modality for clinical cancer therapy. Semiconductor polymer dots (Pdots) doped with photosensitizers have been successfully applied to PDT, and have made progress in the field of tumor therapy. However, the problems of severe photosensitivity and limited tissue penetration depth are needed to be solved during the implementation process of PDT. Here we developed the Pdots doped with photosensitizer molecule Chlorin e6 (Ce6) and photochromic molecule 1,2-bis(2,4-dimethyl-5-phenyl-3-thiophene)-3,3,4,5-hexafluoro-1-cyclopentene (BTE) to construct a photoswitchable nanoplatform for PDT. The Ce6-BTE-doped Pdots were in the green region, and the tissue penetration depth was increased compared with most Pdots in the blue region. The reversible conversion of BTE under different light irradiation was utilized to regulate the photodynamic effect and solve the problem of photosensitivity. The prepared Ce6-BTE-doped Pdots had small size, excellent optical property, efficient ROS generation and good photoswitchable ability. The cellular uptake, cytotoxicity, and photodynamic effect of the Pdots were detected in human colon tumor cells. The experiments in vitro indicated that Ce6-BTE-doped Pdots could exert excellent photodynamic effect in ON state and reduce photosensitivity in OFF state. These results demonstrated that this nanoplatform holds the potential to be used in clinical PDT.

Photodynamic therapy (PDT) dosimetry, including light dose, photosensitizer dose and tissue oxygen, has been a research focus in PDT. In this work, we present a three-dimensional (3D) quantification of protoporphyrin IX (PpIX) using combined spatial frequency domain imaging (SFDI) and diffuse fluorescence tomography (DFT). The SFDI maps both the distributions of tissue absorption and scattering properties at three wavelengths and accordingly provides the optical background for DFT and extracts the tissue oxygenation for assessing the therapeutic outcomes, while DFT dynamically monitors the 3D distribution of PpIX dose from measured fluorescence signals for the procedure optimization. A pilot in vivo application in tumor nude models showed that the proposed SFDI/DFT is able to dynamically trace changes in the PpIX concentration and tissue oxygen during the treatment, rendering it a potentially powerful tool for PDT to improve clinical efficacy.Photodynamic therapy (PDT) dosimetry, including light dose, photosensitizer dose and tissue oxygen, has been a research focus in PDT. In this work, we present a three-dimensional (3D) quantification of protoporphyrin IX (PpIX) using combined spatial frequency domain imaging (SFDI) and diffuse fluorescence tomography (DFT). The SFDI maps both the distributions of tissue absorption and scattering properties at three wavelengths and accordingly provides the optical background for DFT and extracts the tissue oxygenation for assessing the therapeutic outcomes, while DFT dynamically monitors the 3D distribution of PpIX dose from measured fluorescence signals for the procedure optimization. A pilot in vivo application in tumor nude models showed that the proposed SFDI/DFT is able to dynamically trace changes in the PpIX concentration and tissue oxygen during the treatment, rendering it a potentially powerful tool for PDT to improve clinical efficacy.

The discovery of aggregation-induced emission (AIE) effect provides opportunities for the rapid development of fluorescence imaging-guided photodynamic therapy (PDT). In this work, a boron dipyrromethene (BODIPY)-based photosensitizer (ET-BDP-O) with AIE characteristics was developed, in which the two linear arms of BODIPY group were linked with triphenylamine to form an electron Donor–Acceptor–Donor (D–A–D) architecture while side chain was equipped with triethylene glycol group. ET-BDP-O was able to directly self-assemble into nanoparticles (NPs) without supplement of any other matrices or stabilizers due to its amphiphilic property. The as-prepared ET-BDP-O NPs had an excellent colloid stability with the size of 125 nm. Benefiting from the AIE property, ET-BDP-O NPs could generate strong fluorescence and reactive oxygen species under light-emitting diode light irradiation (60mW/cm2). After internalized in cancer cells, ET-BDP-O NPs were able to emit bright red fluorescence signal for bioimaging. In addition, the cell viability assay demonstrated that the ET-BDP-O NPs exhibited excellent photo-cytotoxicity against cancer cells, while negligible cytotoxicity under dark environment. Thus, ET-BDP-O NPs might be regarded as a promising photosensitizer for fluorescence imaging-guided PDT in future.The discovery of aggregation-induced emission (AIE) effect provides opportunities for the rapid development of fluorescence imaging-guided photodynamic therapy (PDT). In this work, a boron dipyrromethene (BODIPY)-based photosensitizer (ET-BDP-O) with AIE characteristics was developed, in which the two linear arms of BODIPY group were linked with triphenylamine to form an electron Donor–Acceptor–Donor (D–A–D) architecture while side chain was equipped with triethylene glycol group. ET-BDP-O was able to directly self-assemble into nanoparticles (NPs) without supplement of any other matrices or stabilizers due to its amphiphilic property. The as-prepared ET-BDP-O NPs had an excellent colloid stability with the size of 125 nm. Benefiting from the AIE property, ET-BDP-O NPs could generate strong fluorescence and reactive oxygen species under light-emitting diode light irradiation (60mW/cm2). After internalized in cancer cells, ET-BDP-O NPs were able to emit bright red fluorescence signal for bioimaging. In addition, the cell viability assay demonstrated that the ET-BDP-O NPs exhibited excellent photo-cytotoxicity against cancer cells, while negligible cytotoxicity under dark environment. Thus, ET-BDP-O NPs might be regarded as a promising photosensitizer for fluorescence imaging-guided PDT in future.

Bacterial resistance is today a matter of great medical concern, so it is urgent to investigate alternatives to alleviate it. Photodynamic inactivation (PDI) is a method that has been endorsed to inactivate different pathogens, including bacteria, fungi and viruses. PDI is achieved by using a photosensitizer (PS) molecule which generates reactive oxygen species under visible or UV radiation. We use visible light and UV-A radiation to excite four commercial PSs (methylene blue, rose bengal, riboflavin and curcumin), and nanoparticles synthesized in our laboratory. Despite these PSs having been thoroughly studied in the past by other research groups, in order to compare their effects in an appropriate way, we matched the number of photons they absorb. We found that methylene blue leads to the major inactivation of Escherichia coli. Furthermore, we evaluated the production of singlet oxygen and hydroxyl radicals in the photoinactivation process.Bacterial resistance is today a matter of great medical concern, so it is urgent to investigate alternatives to alleviate it. Photodynamic inactivation (PDI) is a method that has been endorsed to inactivate different pathogens, including bacteria, fungi and viruses. PDI is achieved by using a photosensitizer (PS) molecule which generates reactive oxygen species under visible or UV radiation. We use visible light and UV-A radiation to excite four commercial PSs (methylene blue, rose bengal, riboflavin and curcumin), and nanoparticles synthesized in our laboratory. Despite these PSs having been thoroughly studied in the past by other research groups, in order to compare their effects in an appropriate way, we matched the number of photons they absorb. We found that methylene blue leads to the major inactivation of Escherichia coli. Furthermore, we evaluated the production of singlet oxygen and hydroxyl radicals in the photoinactivation process.

Singlet oxygen (¹O₂) is the main cytotoxic substance in Type II photodynamic therapy (PDT). The luminescence of ¹O₂ at 1270nm is extremely weak with a low quantum yield, making the direct detection of ¹O₂ at 1270nm very challenging. In this study, a set of highly sensitive optical fiber detection system is built up to detect the luminescence of photosensitized ¹O₂. We use this system to test the luminescence characteristics of ¹O₂ in pig skin tissue ex vivo and mouse auricle skin in vivo. The experimental results show that the designed system can quantitatively detect photosensitized ¹O₂ luminescence. The ¹O₂ luminescence signal at 1270nm is successfully detected in pig skin ex vivo. Compared with RB in an aqueous solution, the lifetime of ¹O₂ increases to 17.4±1.2μs in pig skin tissue ex vivo. Experiments on living mice suggest that an enhancement of ¹O₂ intensity with the increase of the TMPyP concentration. When the dose is 25mg/kg, the vasoconstriction can reach more than 80%. The results of this study hold the potential application for clinical PDT dose monitoring using an optical fiber detection system.Singlet oxygen (¹O₂) is the main cytotoxic substance in Type II photodynamic therapy (PDT). The luminescence of ¹O₂ at 1270nm is extremely weak with a low quantum yield, making the direct detection of ¹O₂ at 1270nm very challenging. In this study, a set of highly sensitive optical fiber detection system is built up to detect the luminescence of photosensitized ¹O₂. We use this system to test the luminescence characteristics of ¹O₂ in pig skin tissue ex vivo and mouse auricle skin in vivo. The experimental results show that the designed system can quantitatively detect photosensitized ¹O₂ luminescence. The ¹O₂ luminescence signal at 1270nm is successfully detected in pig skin ex vivo. Compared with RB in an aqueous solution, the lifetime of ¹O₂ increases to 17.4±1.2μs in pig skin tissue ex vivo. Experiments on living mice suggest that an enhancement of ¹O₂ intensity with the increase of the TMPyP concentration. When the dose is 25mg/kg, the vasoconstriction can reach more than 80%. The results of this study hold the potential application for clinical PDT dose monitoring using an optical fiber detection system.

Photodynamic therapy (PDT) is a minimally invasive method for treating oral leukoplakia. In this paper, we propose a portable PDT device consisting of a flexible circuit board with a liquid flow cooling module on the back. The light source size was 17mm×11mm×4mm, and the irradiation area of the light source was up to 100mm². The irradiance range of this device was from 10mW/cm² to 100mW/cm². Simulation and experimental results showed that the irradiance coefficient variation for a treatment area of 81mm² was less than 7%. At an irradiance of 100mW/cm², a device surface temperature of lower than 42^∘C can be achieved to satisfy the safety requirements under the conditions that the temperature of cooling liquid is 10^∘C and the liquid flow speed is above 12mL/min.Photodynamic therapy (PDT) is a minimally invasive method for treating oral leukoplakia. In this paper, we propose a portable PDT device consisting of a flexible circuit board with a liquid flow cooling module on the back. The light source size was 17mm×11mm×4mm, and the irradiation area of the light source was up to 100mm². The irradiance range of this device was from 10mW/cm² to 100mW/cm². Simulation and experimental results showed that the irradiance coefficient variation for a treatment area of 81mm² was less than 7%. At an irradiance of 100mW/cm², a device surface temperature of lower than 42^∘C can be achieved to satisfy the safety requirements under the conditions that the temperature of cooling liquid is 10^∘C and the liquid flow speed is above 12mL/min.

Targeted photodynamic therapy (TPDT) based on the photosensitizers responsive for tumor microenvironment is promising because of the better anti-tumor effect and less phototoxicity against normal tissue than the traditional PDT. Nanoparticle-based stimuli-responsive photosensitizers have been widely explored for TPDT. Based on the acidic microenvironments in solid tumors, an ultrasmall pH-responsive silicon phthalocyanine nanomicelle (PSN) (smaller than 10nm) was designed for selective PDT of tumor. PSN had high drug loading efficacy (more than 28%) and exhibited morphological transitions, enhanced fluorescence and improved singlet oxygen yield under acidic environments. PSN was renal clearable and could rapidly accumulate and be retained at tumor sites, achieving a tumor-inhibiting effect better than phthalocyanine micelle without pH response. Tumors of mice treated with PSN for PDT were completely ablated without recurrence. Thus, we have developed a phthalocyanine-based pH-responsive micelle with excellent tumor targeting ability, which is expected to realize the selective PDT of tumor.Targeted photodynamic therapy (TPDT) based on the photosensitizers responsive for tumor microenvironment is promising because of the better anti-tumor effect and less phototoxicity against normal tissue than the traditional PDT. Nanoparticle-based stimuli-responsive photosensitizers have been widely explored for TPDT. Based on the acidic microenvironments in solid tumors, an ultrasmall pH-responsive silicon phthalocyanine nanomicelle (PSN) (smaller than 10nm) was designed for selective PDT of tumor. PSN had high drug loading efficacy (more than 28%) and exhibited morphological transitions, enhanced fluorescence and improved singlet oxygen yield under acidic environments. PSN was renal clearable and could rapidly accumulate and be retained at tumor sites, achieving a tumor-inhibiting effect better than phthalocyanine micelle without pH response. Tumors of mice treated with PSN for PDT were completely ablated without recurrence. Thus, we have developed a phthalocyanine-based pH-responsive micelle with excellent tumor targeting ability, which is expected to realize the selective PDT of tumor.