Mechanism Of Photodynamic Therapy Research Articles

Functional Polymer Nanocarriers for Photodynamic Therapy.

Photodynamic therapy (PDT) is an appealing therapeutic modality in management of some solid tumors and other diseases for its minimal invasion and non-systemic toxicity. However, the hydrophobicity and non-selectivity of the photosensitizers, inherent serious hypoxia of tumor tissues and limited penetration depth of light restrict PDT further applications in clinic. Functional polymer nanoparticles can be used as a nanocarrier for accurate PDT. Here, we elucidate the mechanism and application of PDT in cancer treatments, and then review some strategies to administer the biodistribution and activation of photosensitizers (PSs) to ameliorate or utilize the tumor hypoxic microenvironment to enhance the photodynamic therapy effect.

Photodynamic therapy in hypoxia: Near-infrared-sensitive, self-supported, oxygen generation nano-platform enabled by upconverting nanoparticles

Photodynamic therapy (PDT) shows great potential in anti-cancer therapy. The efficiency of PDT is greatly limited by the hypoxia environment in tumors. However, current methods developed to conquer this problem did not accurately produce oxygen for PDT of a certain amount and in a certain position, which could bring a potential risk to normal cells and tissues. Here, upconverting nanoparticles (UCNPs) and gold oxide (Au2O3) were integrated to prepare an efficient, self-supported, oxygen generation nano-platform in a hypoxia environment. Upon a near-infrared (NIR) laser, Au2O3 could produce oxygen assisted by UCNPs through the fluorescence resonance energy transfer (FRET) effect. This light-controlled, self-supported oxygen generation system effectively provided oxygen for the as-loaded photosensitizer chlorin e6 (Ce6) in PDT upon NIR irradiation, which enhanced the inhibition effect of the tumor cells, in both in vitro and in vivo experiments. The present strategy of light-induced, oxygen-producible promoted PDT may solve the long-standing contradiction between the oxygen-dependent working mechanism of PDT and hypoxia microenvironments in tumor cells.

Immune consequences induced by photodynamic therapy in non-melanoma skin cancers: a review.

Photodynamic therapy (PDT) is widely used in dermatology to treat precancerous skin lesions and superficial non-melanoma skin cancers (NMSCs), including premalignant actinic keratosis, cutaneous squamous cell carcinoma in situ, and superficial basal cell carcinoma. The long-term cure rates of PDT range from 70 to 90% in NMSC patients, with excellent cosmetic results and good tolerance. However, the mechanism of action of PDT on tumors is complex. PDT not only kills tumor cells directly but also rapidly recruits immune cells to release inflammatory mediators to activate antitumor immunity. PDT-induced tumor death, also called immunogenic cell death, can trigger both innate and adaptive immune response, further enhancing the antitumor effect. For instance, inoculation of tumor cells killed via PDT to animals triggered a stronger antitumor immunity in vivo than tumor cell lysates produced by other treatments. More importantly, many immunotherapy regimens based on the immune effect of PDT have been developed and demonstrated to be a promising therapeutic method for cancer in pre-clinical trials. Therefore, increasing efforts have been undertaken to investigate the immune responses associated with PDT. In the present review, we first introduce the antitumor effect and the associated mechanisms of PDT in cancers. Then, we summarize studies on the immune responses induced by PDT in NMSCs. We also discuss the potential mechanisms underlying the process.

Discovery and Development of Natural Products and their Derivatives as Photosensitizers for Photodynamic Therapy.

Photodynamic therapy (PDT) has been developed as an alternative modality for the management of neoplastic and nonneoplastic diseases. It is a minimally invasive treatment that involves the interaction of a non-toxic photosensitizer (PS), light and molecular oxygen to generate reactive oxygen species (ROS), resulting in the destruction of unwanted cells and tissues. Discovery and development of new PSs with optimized properties are much crucial for achieving a desirable therapeutic efficacy. This review describes the photochemical and photobiological mechanisms of PDT, and outlines the recent progress in discovery and development of natural products and their derivatives as phototherapeutic drugs. The potential limitations and future perspectives of PDT in clinical application are also presented and discussed.

EGFR-targeted photodynamic therapy by curcumin-encapsulated chitosan/TPP nanoparticles.

BackgroundPhotodynamic therapy (PDT) is an effective therapy for cancers and is a minimally invasive therapy with low dark toxicity and limited side effects. PDT employs the combination of photosensitizers with a specific light source to produce reactive oxygen species (ROS) to damage tumor cells.MethodsWe fabricated nanoparticles encapsulating curcumin through crosslinking chitosan and tripolyphosphate (TPP). Additionally, the chitosan was conjugated to epidermal growth factor in order to target the epidermal growth factor receptor (EGFR), overexpressed on cancer cells. To investigate PDT using fabricated nanoparticles, we measured cell viabilities and ROS production in relation to EGFR-overexpressing gastric cancer cells and non-cancer gastric cells.ResultsThe targeting nanoparticles displayed a superior PDT effect in the cancer cell, with a resultant approximately fourfold decrease in the IC50. The PDT mechanism of curcumin-encapsulated nanoparticles is further identified as the generation of 1O2, the major pathway in PDT.ConclusionThese curcumin-encapsulated chitosan/TPP nanoparticles are a promising targeted-PDT against EGFR-overexpressing cancers.

Photodynamic effect and mechanism study of selenium-enriched phycocyanin from Spirulina platensis against liver tumours

Selenium-containing phycocyanin (Se-PC) has been proved to have many biological effects, including anti-inflammatory and antioxidant. In this study, we investigated the photodynamic therapy (PDT) effects of Se-PC against liver tumour in vitro and in vivo experiment. Our results demonstrated that the half lethal dose of Se-PC PDT on HepG2 cells was 100μg/ml PC containing 20% selenium. Se-PC location migration from lysosomes to mitochondria was time dependent. In in vivo experiments, the tumour inhibition rate was 75.4% in the Se-PC PDT group, compared to 52.6% in PC PDT group. Histological observations revealed that the tumour cells outside the tissue showed cellular necrosis, and those inside the tissue exhibited apoptotic nuclei and digested vacuoles in the cytoplasm after Se-PC PDT treatment. Antioxidant enzyme analysis indicated that GSH-Px activity was linked to the selenium content of Se-PC, and SOD activity was affected by PC PDT. Therefore, Se-PC PDT could induce cell death through free radical production of PDT in tumours and enhance the activity of antioxidant enzymes with selenium in vivo. The mechanism of Se-PC PDT against liver tumour involves hematocyte damage and mitochondria-mediated apoptosis accompanied with autophagy inhibition during early stage of tumour development, which displayed new prospect and offered relatively safe way for cancer therapy.

Therapeutic Considerations and Conjugated Polymer-Based Photosensitizers for Photodynamic Therapy.

Conjugated polymers have recently attracted a great deal of attention for applications in photodynamic therapy (PDT) because of their light-harvesting capability, efficient energy transfer, and singlet oxygen generation properties. This review describes recent advances in PDT development, including therapeutic mechanisms of PDT in cancer treatments, light excitation methods, and especially recent advances of conjugated polyelectrolytes and conjugated polymer nanoparticles as photosensitizers. The future direction on PDT and further development of conjugated polymer photosensitizers are discussed. The aim of this review is to stimulate innovative ideas to synthesize a new generation of conjugated polymer photosensitizers and promote their translation to clinical applications of PDT.

A Computational Way To Achieve More Effective Candidates for Photodynamic Therapy.

The purpose of the work described herein is to design highly efficient photosensitizers (PS) for photodynamic therapy (PDT) in theory. A series of expanded Zn porphyrins have been studied as light-activated PS. Their main photophysical properties are systematically calculated by using density functional theory and its time-dependent extension. The mechanisms of PDT are discussed. All the considered candidates exhibit intense absorption in the therapeutic window (600-800 nm), efficient intersystem crossing, and sufficient energy for singlet molecular oxygen production. Accordingly, the designed Zn pentaphyrins and sapphyrins would be proposed as potential PS for PDT. Moreover, the therapeutic effects of Zn pentaphyrins and sapphyrins are better than those of the referenced Zn iso-pentaphyrin. It is expected that the results could provide a new way to design and develop PS for PDT application.

Photodynamic therapy monitoring with optical coherence angiography

Photodynamic therapy (PDT) is a promising modern approach for cancer therapy with low normal tissue toxicity. This study was focused on a vascular-targeting Chlorine E6 mediated PDT. A new angiographic imaging approach known as M-mode-like optical coherence angiography (MML-OCA) was able to sensitively detect PDT-induced microvascular alterations in the mouse ear tumour model CT26. Histological analysis showed that the main mechanisms of vascular PDT was thrombosis of blood vessels and hemorrhage, which agrees with angiographic imaging by MML-OCA. Relationship between MML-OCA-detected early microvascular damage post PDT (within 24 hours) and tumour regression/regrowth was confirmed by histology. The advantages of MML-OCA such as direct image acquisition, fast processing, robust and affordable system opto-electronics, and label-free high contrast 3D visualization of the microvasculature suggest attractive possibilities of this method in practical clinical monitoring of cancer therapies with microvascular involvement.

Plasmon-Enhanced Photodynamic Cancer Therapy by Upconversion Nanoparticles Conjugated with Au Nanorods.

Photodynamic therapy (PDT) based on photosensitizers (PSs) constructed with nanomaterials has been widely applied to treat cancer. This therapy is characterized by an improved PS accumulation in tumor regions. However, challenges, such as short penetration depth of light and low extinction coefficient of PSs, limit PDT applications. In this study, a nanocomposite consisting of NaYF4:Yb/Er upconversion nanoparticles (UCPs) conjugated with gold nanorods (Au NRs) was developed to improve the therapeutic efficiency of PDT. Methylene blue (MB) was embedded in a silica shell for plasmon-enhanced PDT. UCPs served as a light converter from near-infrared (NIR) to visible light to excite MB to generate reactive oxygen species (ROS). Au NRs could effectively enhance upconversion efficiency and ROS content through a localized surface plasmon resonance (SPR) effect. Silica shell thickness was adjusted to investigate the optimized MB loading amount, ROS production capability, and efficient distance for plasmon-enhanced ROS production. The mechanism of plasmon-enhanced PDT was verified by enhancing UC luminescence intensity through the plasmonic field and by increasing the light-harvesting capability and absorption cross section of the system. This process improved the ROS generation by comparing the exchange of Au NRs to Au nanoparticles with different SPR bands. NIR-triggered nanocomposites of UCP@SiO2:MB-NRs were significantly confirmed by improving ROS generation and further modifying folic acid (FA) to develop an active component targeting OECM-1 oral cancer cells. Consequently, UCP@SiO2:MB-NRs-FA could highly produce ROS and undergo efficient PDT in vitro and in vivo. The mechanism of PDT treatment by UCP@SiO2:MB-NRs-FA was evaluated via the cell apoptosis pathway. The proposed process is a promising strategy to enhance ROS production through plasmonic field enhancement and thus achieve high PDT therapeutic efficacy.

Phototoxic effects of silicon bis (dimetilaminoetanoxi)-phthalocyanine (SiPc) on the viability of Leishmania major and Leishmania braziliensis promastigotes

American cutaneous leishmaniasis (ACL) is an infectious disease caused by protozoans of the genus Leishmania. The treatment may consist of pentavalent antimonials or pentamidine and amphotericin. However, these treatments are extremely aggressive. Photodynamic antimicrobial chemotherapy (PACT) involves the same mechanism of photodynamic therapy which associates a photosensitizer with oxygen and a light source generating a photochemical reaction leading to cell death. The aim of this study was to verify the potential use of silicon bis (dimetilaminoetanoxi)-phthalocyanine (SiPc) compound in photodynamic treatment through evaluation of its phototoxic effect in promastigotes of the genus Leishmania braziliensis and Leishmania major. Treatment with SiPc was able to drastically affect the viability of the parasites as well as affect their growth and morphology, after PACT treatment. The data shown in this study allows us to conclude that SiPc is a promising photosensitizer (PS) since it does not affect parasite growth and viability in the dark. After PACT with this phthalocyanine, over 99% of parasites were killed with the higher concentration and a light dose used. These results suggest that SiPc can be used in future to treat CL, however, further studies are necessary to determine whether the PS are toxic to mononuclear phagocytic cells and epithelial cells which will also be affected by therapy when applied topically.

Time course of apoptosis induced by photodynamic therapy with PsD007 in LT12 acute myeloid leukemia cells.

Apoptosis is one of the major mechanisms of photodynamic therapy (PDT) that leads to tumor degradation. Apoptosis-related genes and proteins function in a certain order and timing in the complex network of apoptosis. To further understanding of the apoptotic mechanism of PDT, this research examined the time course of apoptosis from PsD007 (a second-generation photosensitizer developed in China) induced PDT on the rat acute myeloid leukemia cell line LT12. MTT was used to detect the temporal dynamic of PDT killing effects and identified the "apoptotic window" of 2-24h. Apoptosis showed a basal peak at 2h, and the duration of apoptosis depended on PDT dose, which disappeared quickly at low concentrations but lasted to higher levels to 6 or 12h at high concentrations as detected by flow cytometry. High-content imaging confirmed these results. An 84-gene apoptosis PCR array identified 15 genes with an expression level change of over twofold at 6h post-PDT. Nine apoptosis-related genes showed changes in expression at 2-12h after PDT. TNF family genes TNF and FASLG showed a maximal change of 3.47- and 4.42-fold from baseline. Key apoptosis proteins such as activated caspases showed strong up-regulation after PDT, with the expression peaks of cleaved caspase-7, caspase-9 and PARP at 4-6h, and cleaved caspase-3 delayed to 6-12h. Our findings help clarify the time course of apoptosis events in response to PDT treatment in a leukemia cell line and may help contribute to the clinical application of PDT in leukemia treatment.

THE USE OF PHOTOD YNAMIC THERAPY IN THE DOMESTIC ONCOLOGY. (REVIEW OF THE LITERA TURE)

In this paper, it has been tasked to demonstrate progress is Russian scientists who are pioneers in the application of clinical photodynamic therapy (PDT) in Europe. In this review current understanding of the mechanisms of action PDT on the tumor and the body, the technical aspects of the application of the laser radiation of varying intensity, particularly its effect on biological tissues. The results of studies on the use of PDT with different photosensitizers in the complex therapeutic measures in patients with cancer. The data on the efficacy and safety of PDT. Given the effectiveness of PDT and ease of use, no adverse reactions, this medical technology can be attributed to one of the most promising trends in oncology. Accumulated a large experience of PDT in oncology testifies to high efficiency of this method in the treatment of various tumors. However, despite the positive results obtained in clinical practice, PDT in oncology is not widely used. It is proposed to implement this knowledge into the educational process at universities. Researchers of the А. Tsyb MRRC and Obninsk Institute for Nuclear Power Engineering (MEPhI) are working under development of educational complex program «Medical physics». This cooperation is expected to improve professional training and education in health physics.

Enhancing Photodynamic Therapy Efficacy by Using Fluorinated Nanoplatform

Photodynamic therapy (PDT) is a noninvasive therapeutic modality with fast healing process and little or no scarring. The production of reactive oxygen species is highly dependent on oxygen concentration, and thus, the therapeutic efficacy of PDT would be retarded by inefficient oxygen supply in hypoxic tumor cell and the oxygen self-consuming mechanism of PDT. It is well-known that perfluorocarbons are endowed with properties of enhanced oxygen solubility and transfer capacity. Herein, we prepared a series of nanoplatforms of spherical micelles with different ratios of pentafluorophenyl to porphyrin in the core and utilized these micelles as models to examine the influence of content of fluorinated segments on the PDT effect of porphyrins. It was found for the first time, as far as we are aware, that the production efficacy of singlet oxygen increased with the rising in the ratio of pentafluorophenyl to porphyrin. Thus, this work presents a new avenue to improve PDT efficacy by enhancing oxygen solubility and diffusivity of nanoplatforms with the incorporation of perfluorocarbon segments.

Activatable Ferritin Nanocomplex for Real-Time Monitoring of Caspase-3 Activation during Photodynamic Therapy.

One mechanism of photodynamic therapy (PDT) for the ablation of tumors is to induce apoptosis. Visualization of apoptosis during PDT in real-time is of great benefit for predicting and evaluating therapeutic outcomes. Herein, we engineered a highly stable and sensitive caspase-3 ferritin activatable probe (FABP/ZnPc) for simultaneous delivery of a photosensitizer (ZnPc) and real-time visualization of apoptosis during PDT. Upon near-infrared (NIR) light irradiation, ZnPc becomes active and initiates apoptosis, upon which the outer layer of the FABP/ZnPc is degraded by the apoptotic marker, caspase-3, to boost strong fluorescent signals, ultimately allowing real-time imaging of apoptosis. Our results demonstrate the utility of FABP/ZnPc as a tool for PDT and simultaneous imaging of caspase-3 activation in vitro and in vivo. Overall, the ability of FABP/ZnPc to image apoptosis during PDT will not only facilitate optimizing and personalizing the PDT strategy but is also important for understanding the mechanisms of PDT.

Apoptosis of HeLa cells induced by a new targeting photosensitizer-based PDT via a mitochondrial pathway and ER stress.

Photodynamic therapy (PDT) is emerging as a viable treatment for many cancers. To decrease the cutaneous photosensitivity induced by PDT, many attempts have been made to search for a targeting photosensitizer; however, few reports describe the molecular mechanism of PDT mediated by this type of targeting photosensitizer. The present study aimed to investigate the molecular mechanism of PDT induced by a new targeting photosensitizer (PS I), reported previously by us, on HeLa cells. Apoptosis is the primary mode of HeLa cell death in our system, and apoptosis occurs in a manner dependent on concentration, irradiation dose, and drug–light intervals. After endocytosis mediated by the folate receptor, PS I was primarily localized to the mitochondria and the endoplasmic reticulum (ER) of HeLa cells. PS I PDT resulted in rapid increases in intracellular reactive oxygen species (ROS) production and Ca2+ concentration, both of which reached a peak nearly simultaneously at 15 minutes, followed by the loss of mitochondrial membrane potential at 30 minutes, release of cytochrome c from mitochondria into the cytoplasm, downregulation of Bcl-2 expression, and upregulation of Bax expression. Meanwhile, activation of caspase-3, -9, and -12, as well as induction of C/EBP homologous protein (CHOP) and glucose-regulated protein (GRP78), in HeLa cells after PS I PDT was also detected. These results suggest that apoptosis of HeLa cells induced by PS I PDT is not only triggered by ROS but is also regulated by Ca2+ overload. Mitochondria and the ER serve as the subcellular targets of PS I PDT, the effective activation of which is responsible for PS I PDT-induced apoptosis in HeLa cells.

Hypericin-mediated photodynamic therapy induces apoptosis of myoloma SP2/0 cells depended on caspase activity in vitro.

BackgroundPhotodynamic therapy (PDT) is becoming a promising therapeutic modality for hematological malignancies. Hypericin is a natural photosensitizer possessing anti-depressant, anti-virus and anti-cancer activities. The present study was designed to explore the effect and mechanism of hypericin-mediated PDT on the mouse multiple myeloma (MM) cells in vitro.MethodsThe mouse myeloma SP2/0 cells were incubed with different concentrations of hypericin and then illuminated with different light doses. The inhibitory effect of hypericin-mediated PDT on tumor cell proliferation was assayed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) method. The apoptosis related morphological changes of SP2/0 cells were observed by microscopy. The biochemical hallmarks of apoptosis such as DNA fragments, mitochondrial membrane potential changes were assessed. The expression of apoptosis related proteins were investigated by western blotting.ResultsHypericin-mediated PDT induced the proliferation inhibition and apoptosis of tumor cells in a dose dependent manner. Tumor cells showed obvious morphological changes of apoptosis and necrosis and DNA fragmentation after treated by hypericin mediated PDT (0.025 ~ 0.05 μM). The mitochondria membrane potential in SP2/0 cells was decreased significantly after incubated with the 0.025 μM and 0.5 μM hypericin (P < 0.05). The expression level of caspase-3 was decreased, while caspase activity was elevated with the increasing drug dosage. The apoptosis of SP2/0 cells was blocked by a pan-caspase inhibitor Z-VAD-FMK and caspase-3 inhibitor Ac-DEVD-CHO.ConclusionHypericin-mediated PDT induced apoptosis mainly dependent on caspase related pathways. Hypericin-mediated PDT may be a potential and alternative therapy for MM.

C-MYC and C-FOS expression changes and cellular aspects of the photodynamic reaction with photosensitizers TMPyP and ClAlPcS2

Photodynamic therapy (PDT) is based on the tumor-selective accumulation of photosensitizer followed by irradiation with light of an appropriate wavelength. After irradiation and in the presence of oxygen, photosensitizer induces cellular damage. The aim of this study was to evaluate effects of two photosensitizers TMPyP and ClAlPcS2 on cell lines to obtain better insight into their mechanisms of action. We determined cell viability, reactive oxygen species (ROS) generation and changes in expression levels of two important early response genes, C-MYC and C-FOS, on tumor MCF7 (human breast adenocarcinoma) and G361 (human melanoma) cell lines and non-tumor BJ cell line (human fibroblast) after photodynamic reaction with TMPyP and ClAlPcS2 as photosensitizers. In addition TMPyP and ClAlPcS2 cellular uptake and clearance and antioxidant capacity of the mentioned cell lines were investigated. We found appropriate therapeutic doses and confirmed that both tested photosensitizers are photodynamically efficient in treatment used cells in vitro. TMPyP is more efficient; it had higher ROS production and toxicity after irradiation by intermediate therapeutic doses than ClAlPcS2. We revealed that both TMPyP and ClAlPcS2-PDT increased C-FOS expression on tumor cell lines (G361 and MCF7), but not on non-tumor BJ cell line. Conversely, both TMPyP and ClAlPcS2-PDT decreased C-MYC expression on non-tumor BJ cell line but not on tumor cell lines. As first we tested these photosensitizers in such extent and we believe that it can help to better understand mechanisms of PDT and increase its efficiency and applicability.

Hypericin-mediated photodynamic therapy induces apoptosis of myoloma SP2/0 cells depended on caspase activity in vitro

Photodynamic therapy (PDT) is becoming a promising therapeutic modality for hematological malignancies. Hypericin is a natural photosensitizer possessing anti-depressant, anti-virus and anti-cancer activities. The present study was designed to explore the effect and mechanism of hypericin-mediated PDT on the mouse multiple myeloma (MM) cells in vitro. The mouse myeloma SP2/0 cells were incubed with different concentrations of hypericin and then illuminated with different light doses. The inhibitory effect of hypericin-mediated PDT on tumor cell proliferation was assayed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) method. The apoptosis related morphological changes of SP2/0 cells were observed by microscopy. The biochemical hallmarks of apoptosis such as DNA fragments, mitochondrial membrane potential changes were assessed. The expression of apoptosis related proteins were investigated by western blotting. Hypericin-mediated PDT induced the proliferation inhibition and apoptosis of tumor cells in a dose dependent manner. Tumor cells showed obvious morphological changes of apoptosis and necrosis and DNA fragmentation after treated by hypericin mediated PDT (0.025 ~ 0.05 μM). The mitochondria membrane potential in SP2/0 cells was decreased significantly after incubated with the 0.025 μM and 0.5 μM hypericin (P < 0.05). The expression level of caspase-3 was decreased, while caspase activity was elevated with the increasing drug dosage. The apoptosis of SP2/0 cells was blocked by a pan-caspase inhibitor Z-VAD-FMK and caspase-3 inhibitor Ac-DEVD-CHO. Hypericin-mediated PDT induced apoptosis mainly dependent on caspase related pathways. Hypericin-mediated PDT may be a potential and alternative therapy for MM.

Magnetic-luminescent YbPO4:Er,Dy microspheres designed for tumor theranostics with synergistic effect of photodynamic therapy and chemotherapy

In this paper, magnetic and fluorescent bifunctional YbPO4:Er,Dy microspheres were synthesized via a simple solvothermal method. The prepared microspheres exposed to 980 nm near-infrared (NIR) laser light emitted bright upconversion fluorescence (450–570 nm) after calcination at high temperatures (>800°C). Results of magnetic resonance studies demonstrated that the YbPO4:Er,Dy microspheres are more suitable to be used as a transverse relaxation time (negative) contrast magnetic resonance imaging agent. The microspheres successfully entered the human hepatocellular carcinoma cells and presented low toxicity. A well-selected photodynamic therapy (PDT) drug, merocyanine 540 (MC540) with an ultraviolet–visible spectroscopy absorption maximum of 540 nm, was loaded onto the microspheres to obtain YbPO4:Er,Dy-MC540. Since the upconversion fluorescence emitting from the microspheres could be absorbed by MC540 with a small absorption/emission disparity, YbPO4:Er,Dy-MC540 could kill the hepatocellular carcinoma cells via PDT mechanism effectively. In other words, being upconverting particles, the prepared microspheres acted as light transducers in the NIR light-triggered PDT process. A chemotherapy drug, doxorubicin, was further loaded onto YbPO4:Er,Dy-MC540 to achieve enhanced antitumor effect based on synergistic therapeutic efficacy of PDT and chemotherapy. It is expected that the prepared YbPO4:Er,Dy microspheres have applications in tumor theranostics including magnetic-fluorescent bimodal imaging and NIR light-triggered PDT.