Anthropogenic activities enhance mercury methylation in sediments of a multifunctional lake: Evidence from dissolved organic matter and mercury-methylating microorganisms.

Multifunctional lakes are highly susceptible to anthropogenic influences, potentially introducing exogenous pollutants or nutrients into aquatic sediments. This, in turn, affects the mercury (Hg) methylation in the sediments. This study was conducted in the Changshou Lake, a representative multifunctional lake in southwestern China, with a specific focus on investigating the Hg variations, the potential of Hg methylation, and the influential factors affecting the methylation process within sediments across different functional areas. The results revealed significant variations in total Hg concentrations between the ecological culture area (area I), the ecological tourism area (area II), and the wetland protection area (area III), suggesting the possibility of exogenous Hg introduction associated with human activities. Furthermore, sediments from areas I and II displayed a greater potential for Hg methylation. This was ascribed to the enhanced diversity and relative abundance of Hg-methylating microorganisms, especially Geobacteraceae, induced by elevated levels of dissolved organic carbon in these two areas from human activities like historical cage culture. This study provides evidence that anthropogenic activities enhance the process of Hg methylation in the sediments of multifunctional lakes, highlighting the necessity of implementing comprehensive scientific water quality management practices to mitigate the negative impacts of human influences on these unique ecosystems.

Distribution and Release of Mercury Regulated by the Decomposition of a Pioneer Habitat-Adapted Plant in the Water-Level-Fluctuating Zone of the Three Gorges Reservoir.

Pioneer habitat-adapted bermudagrass is prevalent in the water-level-fluctuating zone of the Three Gorges Reservoir area. This study was performed to explore the response characteristics of dissolved organic matter (DOM) qualities to bermudagrass decomposition and their regulation in the distribution and release of mercury (Hg) and methylmercury (MeHg) in the soil-water system. Compared to the control, the bermudagrass decomposition resulted in a great increase in the protein-like components in the water in the initial stages (p < 0.01), but it also greatly reduced the humification degree of water DOM (p < 0.01). However, it accelerated the consumption of protein-like components, the humification rate, and the synthesis of humic-like DOM in the water over time. This changing pattern of the DOM qualities resulted in an initial elevation and a subsequent great decrease in the dissolved Hg and MeHg concentrations in the pore water, which ultimately reduced their release levels into the overlying water by 26.50% and 54.42%, respectively, compared to the control. Our results indicate the potential inhibitory effects of short-term bermudagrass decomposition caused by flooding and how decomposition affects the release of total Hg and MeHg by shaping the DOM qualities, and they have implications for similar aquatic systems in which herbaceous plants are frequently decomposed after submergence.

Novel molecular photosensitizer with simultaneously GSH depletion, aggregation inhibition and accelerated elimination for improved and safe photodynamic therapy.

The major challenges in photodynamic therapy (PDT) are the neutralization of cytotoxic reactive oxygen species (ROS) by the excessive antioxidant glutathione (GSH) in tumor cells, high self-aggregation of most photosensitizers (PSs), and long time to protect from light after treatment. Thus, to develop the molecular PSs for the improved and safe PDT in clinic, a novel and versatile PS (Mal-Pc) has been designed by di-substituting maleimides to the axial positions of silicon (Ⅳ) phthalocyanine. Owning to the conjugation of maleimides, Mal-Pc can not only entry tumor cells more easily and faster, but also can react with the intracellular overexpressed GSH after entry. In addition, upon electrophilic reaction with GSH, the inhibition of self-aggregation of Mal-Pc has been demonstrated by the restoration of the fluorescence emission in aqueous media. As a result, the intracellular ROS levels and photocytotoxicity of Mal-Pc are dramatically enhanced. Finally, the high hydrophilicity of the product GS-conjugates facilitates Mal-Pc eliminate from the normal cells more rapidly. Overall, this work revealed the high potential of the versatile molecular Mal-Pc for highly efficient and safe PDT in clinical translation.

Targeted Drug Delivery System Based on Copper Sulfide for Synergistic Near-Infrared Photothermal Therapy/Photodynamic Therapy/Chemotherapy of Triple Negative Breast Cancer.

Multi-modal synergistic therapy, especially the integration of near-infrared laser phototherapies and chemotherapy, is often sought after owing to its minimal invasiveness, low side effects, and improved anticancer therapeutic efficacy. Herein, CuS nanoparticles were first coated with zinc phthalocyanine derivant (Pc)-functionalized mesoporous silica (mSiO2-Pc) to achieve a drug delivery system (CuS@mSiO2-Pc) with photothermal/photodynamic therapy. Chemical drug DOX was subsequently loaded for chemotherapy, and hyaluronic acid (HA) was employed as a covering material with cancer targeting. The as-obtained CuS@mSiO2-Pc(DOX)@HA nanoparticles were nano-sized with good biocompatibility, effective DOX loading, and controllable DOX releasing. Expectedly, this multifunctional nanoplatform exhibits effective generation of reactive oxygen species and hyperthermia upon the near-infrared laser irradiation. Most importantly, the nanoparticles were targeted into 4T1 cells and showed significantly remarkable cytotoxicity under near-infrared laser irradiation, proving their synergistic therapeutic efficacy. Therefore, this targeted drug system based on CuS with synergistic photothermal therapy/photodynamic therapy/chemotherapy has great application prospects in clinical anticancer treatment for triple negative breast cancer.

A MCL-1-targeted photosensitizer to combat triple-negative breast cancer with enhanced photodynamic efficacy, sensitization to ROS-induced damage, and immune response.

As growth factor receptor-2 (HER-2), progesterone receptor (PR) and estrogen receptor (ER) are scarce in triple-negative breast cancer (TNBC), it is a great challenge to combat TNBC with high tumor specificity and therapeutic efficacy. Most traditional treatments including surgical resection, chemotherapy, and radiotherapy would more or less cause serious side effects and drug resistance. Photodynamic therapy (PDT) has huge potential in the treatment of TNBC for minimal invasiveness, low toxicity, less drug resistance and high spatiotemporal selectivity. Inspired by the advantages of small-molecule-targeted PDT and the sensitization effect of myeloid cell leukemia-1 (MCL-1) inhibitor, a novel photosensitizer BC-Pc was designed by conjugating MCL-1 inhibitor with zinc phthalocyanines. Owning to 3-chloro-6-methyl-1-benzothiophene-2-carboxylic acid (BC) moiety, BC-Pc exhibits the high affinity towards MCL-1 and reduce its self-aggregation in TNBC cells. Therefore, MCL-1 targeted BC-Pc showed remarkable intracellular fluorescence and ROS generation in TNBC cells. Additionally, BC-Pc can selectively sensitize TNBC cells to ROS-induced damage, resulting in improved therapeutic effect to TNBC cells and negligible toxicity to normal cells. More importantly, BC-Pc can effectively inhibit the migration and invasion of TNBC cells, and enhance immune response, all of which will be beneficial to eradicate TNBC. To the best of our knowledge, BC-Pc is the novel MCL-targeted photosensitizer, which owns the amplified ROS-induced lethality and anticancer immune response for TNBC. Overall, our study provides a promising strategy to achieve targeting and highly efficient therapy of TNBC.

Role of the rhizosphere of a flooding-tolerant herb in promoting mercury methylation in water-level fluctuation zones.

The water-level fluctuation zone (WLFZ) has been considered as a hotspot for mercury (Hg) methylation. Flooding-tolerant herbs are gradually acclimated to this water-land ecotone, tending to form substantial root systems for improving erosion resistance. Accompanying rhizosphere microzone plays crucial but unclear roles in methylmercury (MeHg) formation in the WLFZ. Thus, we conducted this study in the WLFZ of the Three Gorges Reservoir, to explore effects of the rhizosphere of a dominant flooding-tolerant herb (bermudagrass) on MeHg production. The elevated Hg and MeHg in rhizosphere soils suggest that the rhizosphere environment provides favorable conditions for Hg accumulation and methylation. The increased bioavailable Hg and microbial activity in the rhizosphere probably serve as important factors driving MeHg formation in the presence of bermudagrass. Simultaneously, the rhizosphere environments changed the richness, diversity, and distribution of hgcA-containing microorganisms. Here, a typical iron-reducing bacterium (Geobacteraceae) has been screened, however, the majority of hgcA genes detected in rhizosphere, near-, and non-rhizosphere soils of the WLFZ were unclassified. Collectively, these results provide new insights into the elevated MeHg production as related to microbial processes in the rhizosphere of perennial herbs in the WLFZ, with general implications for Hg cycling in other ecosystems with water-level fluctuations.

A phthalocyanine-based photosensitizer for effectively combating triple negative breast cancer with enhanced photodynamic anticancer activity and immune response.

Although photodynamic therapy (PDT) has attracted great interest, the photosensitizers in clinical had weak inhibition on metastasis and invasion of cancers. Additionally the immune response induced by PDT was insufficient to eradicate cancer. Herein, indoximod, an inhibitor of indoleamine 2,3-dioxygenase (IDO), is introduced to concatenate with zinc phthalocyanines (ZnPc) for effectively overcoming above inadequacy. Due to indoximod moiety, photosensitizer 1-MT-Pc can obtain enhanced intracellular uptake and high reactive oxygen species (ROS) generation. More impressively, 1-MT-Pc can achieve remarkable photocytotoxicity towards TNBC cells and negligible damage to normal cells. Meanwhile, 1-MT-Pc effectively inhibits metastasis and invasion of TNBC cells. Importantly, 1-MT-Pc exhibit elevated inhibitory effect on 4T1 tumor by enhanced PDT and immunotherapy.

Fluorescence-Reporting-Guided Tumor Acidic Environment-Activated Triple Photodynamic, Chemodynamic, and Chemotherapeutic Reactions for Efficient Hepatocellular Carcinoma Cell Ablation.

Tumor acidic environment-activated combination therapy holds great promise to significantly decrease side effects, circumvent multiple drug resistance, and improve therapeutic outcomes for cancer treatment. Herein, Sorafenib/ZnPc(PS)4@FeIII-TA nanoparticles (SPFT) are designed with acid-environment turned-on fluorescence to report the activation of triple therapy including photodynamic, chemodynamic, and chemotherapy on hepatocellular carcinoma. The SPFT are composed of SP cores formulated via self-assembly of sorafenib and ZnPc(PS)4, with high drug loading efficiency, and FeIII-TA shells containing FeCl3 and tannic acid. Importantly, the nanoparticles suppress reactive oxygen species (ROS) generation of ZnPc(PS)4 due to their formation in nanoparticles, while assisting simultaneous uptake of the uploaded drugs in cancer cells. The tumor acidic environment initiates FeIII-TA decomposition and accelerates a chemodynamic reaction between FeII and H2O2 to generate toxic •OH. Then, the SP core is decomposed to separate ZnPc(PS)4 and sorafenib, which leads to fluorescence turning-on of ZnPc(PS)4, expedited photodynamic reactions, and burst release of sorafenib. Notably, SPFT shows low dark cytotoxicity to normal cells but exerts high potency on hepatocellular carcinoma cells under near-infrared light irradiation, which is much more potent than either sorafenib or ZnPc(PS)4 alone. This research offers a facile nanomedicine design strategy for cancer therapy.

Using porphyrins as albumin-binding molecules to enhance antitumor efficacies and reduce systemic toxicities of antimicrobial peptides.

Antimicrobial peptides (AMPs) are originally developed for anti-infective treatments. Because of their membrane-lytic property, AMPs have been considered as candidates of antitumor agents for a long time. However, their antitumor applications are mainly hampered by fast renal clearance and high systemic toxicities. This study proposes a strategy aiming at addressing these two issues by conjugating AMPs with porphyrins, which bind to albumin increasing AMPs' resistance against renal clearance and thus enhancing their antitumor efficacies. Porphyrins' photodynamic properties can further augment AMPs' antitumor effects. In addition, circulating with albumin ameliorates AMPs' systemic toxicities, i.e. hemolysis and organ dysfunctions. As an example, we conjugated an AMP, K6L9, with pyropheophorbide-a (PPA) leading to a conjugate of PPA-K6L9. PPA-K6L9 bound to albumin with a KD value at the sub-micromolar range. Combining computational and experimental approaches, we characterized the molecular interaction of PPA-K6L9 with albumin. Furthermore, PPA-conjugation promoted K6L9' antitumor effects by prolonging its in vivo retention time, and reduced the hemolysis and hepatic injuries, which confirmed our design strategy.

A Study on Hair Mercury Levels of University Students.

Total mercury (THg) and methylmercury (MeHg) concentrations were measured in hair of 98 Chinese university students to study their levels of Hg exposure and influencing factors. The results showed that Hg exposure for university students was at a low level with concentrations lower than the USEPA recommended reference level (1 µg/g) across all hair samples. The percentage of MeHg to THg (%MeHg) in hair was about 50%, lower than the previously reported value of 70-100%, probably associated with the low %MeHg in the diet of university students. Fish and rice consumption were not a primary factor affecting hair Hg levels of university students, while smoking could be one main pathway of Hg exposure. In addition, the similarly dietary structure in the studied university narrowed the difference of Hg exposure levels among students.

Novel Targeted Photosensitizer as an Immunomodulator for Highly Efficient Therapy of T-Cell Acute Lymphoblastic Leukemia.

Dasatinib is a kinase-targeted drug used in the treatment of leukemia. Regrettably, it remains far from optimal medicine due to insurmountable drug resistance and side effects. Photodynamic therapy (PDT) has proven that it can induce systemic immune responses. However, conventional photosensitizers as immunomodulators produce anticancer immunities, which are inadequate to eliminate residual cancer cells. Herein, a novel compound 4 was synthesized and investigated, which introduces dasatinib and zinc(II) phthalocyanine as the targeting and photodynamic moiety, respectively. Compound 4 exhibits a high affinity to CCRF-CEM cells/tumor tissues, which overexpress lymphocyte-specific protein tyrosine kinase (LCK), and preferential elimination from the body. Meanwhile, compound 4 shows excellent photocytotoxicity and tumor regression. Significantly, compound 4-induced PDT can obviously enhance immune responses, resulting in the production of more immune cells. We believe that the proposed manner is a potential strategy for the treatment of T-cell acute lymphoblastic leukemia.

Improved photodynamic anticancer activity and mechanisms of a promising zinc(II) phthalocyanine-quinoline conjugate photosensitizer in vitro and in vivo.

Since the discovery of photodynamic therapy, scientists have constantly been searching for more effective and ideal photosensitizers (PSs). As part of our ongoing interest in the development of more potent photosensitizers, quinoline-8-yloxy-substituted zinc(II) phthalocyanine (ZnPc-Q1) has been identified as a promising photosensitizers in tumor cells. This study aims to explore the photodynamic mechanism and in vivo photodynamic efficacy of ZnPc-Q1, and further evaluate its potential in clinical photodynamic therapy application. The single crystal structure of ZnPc-Q1 enables the easy control of clinical quality standards. In comparison with Photofrin, ZnPc-Q1 exhibits considerably higher in vitro anticancer activity by dual dose-related mechanisms (antiproliferative and apoptosis). In addition, the in vivo results demonstrate that ZnPc-Q1 exhibits significant tumor regression with less skin photosensitivity by both direct killing and apoptosis anticancer mechanisms. In conclusion, ZnPc-Q1 can be considered to be a promising ideal PS for clinical application owing to its defined chemical structure without phthalocyanine isomerization, good absorption of tissue-penetrating red light, improved photodynamic therapy efficacy, and reduced skin phototoxicity.

Blood distribution and plasma protein binding of PHOTOCYANINE: a promising phthalocyanine photosensitizer inphaseâ ¡ clinical trials.

Blood distribution and plasma protein binding are the important properties that can influence pharmacokinetics and ultimately the anticancer efficacy of photosensitizers in clinical photodynamic therapy. As a novel and promising phthalocyanine photosensitizer under clinical phase Ⅱ investigation in China, the superiority of PHOCYANINE is speculated on its attribution to its binding with plasma proteins. To verify this hypothesis, explore the targeting mechanism and further apply foundation for its clinical trial evaluation, we further study its in vitro and in vivo human blood distribution, in vitro plasma protein and lipoprotein binding in detail. PHOTOCYANINE was found to be mainly distributed in plasma with low KBP and KEP values. Moreover, its high binding rates to plasma proteins among various species (mouse, rat, dog, monkey, and human) were then determined. Among these plasma proteins, human serum albumin and α1-acid-glycoprotein were found to bind PHOTOCYANINE highly, and low-density lipoproteins have the highest percentage of PHOTOCYANINE over other lipoproteins. This study is expected to provide some guidance for PDT clinical evaluations and for further molecular design and development of photosensitizers.

A phase Ι study to evaluate the application of photocyanine using pharmacokinetic and pharmacodynamic analysis in patients with malignancy.

PURPOSE: Photodynamic therapy (PDT) schedules are based on sensitiser dose, light dose, and drug-light interval. The aim of the phase Ι study was to choose optimal dose and drug-light interval for PDT with photocyanine using pharmacokinetics (PK) and pharmacodynamics (PD). METHODS: Twenty-eight cancer patients were enrolled. In trial A, 12 patients received one of four ascending doses of photocyanine intravenously 24 h prior to 180-270 J/cm2 illumination. 0.2 mg/kg dose was infused to ten patients 12-48 h prior to 120 J/cm2 illumination in trial B. In trial C, 0.1 mg/kg dose was infused to six patients 6 or 12 h prior to 180-270 J/cm2 illumination. Serum concentrations of photocyanine were measured, and simulations were performed to assess the effect of drug exposure in tissue on responses. RESULTS: Analysis of photocyanine levels of patients indicated that the two-compartment model best fit the data. Simulations showed that the rates of the drug entering tissues and leaving tissues were equal at 8-12 h after injection. Patients experienced pain which was related to photocyanine serum levels, especially with serum levels above 2500 ng/ml. Fewer non-responders were observed at serum levels higher than 1000 ng/ml for illumination at least 12 h after administration. CONCLUSION: It is the first report of human trials of photocyanine, and the results suggested that patients receive 180 J/cm2 illumination about 20-30 min at serum concentrations of photocyanine between 1000 and 2500 ng/ml at least 10 h after administration.

Enhanced Synergistic Antibacterial Activity through a Smart Platform Based on UiO-66 Combined with Photodynamic Therapy and Chemotherapy.

Harmful bacteria have seriously threatened human health and wealth for a long time. Herein, a multifunctional drug delivery system based on UiO-66 was fabricated, and it showed potent synergistic antibacterial effects when used in conjunction with photodynamic therapy and chemotherapy. First, UiO-66-NH2 was prepared via a facile solvothermal method. Then, carboxylic zinc phthalocyanine, a broad-spectrum photosensitizer, was connected to UiO-66-NH2 by amidation. Next, synergistic chemical antibiotic linezolid was loaded in the pores, and lysozyme was coated on the surface by electrostatic interactions. In vitro antibacterial experiments were then carried out to evaluate the antibacterial effects of this system against three kinds of bacteria, Staphylococcus aureus, Escherichia coli, and methicillin-resistant S. aureus (MRSA). The combination of lysozyme, linezolid, and singlet oxygen generated by irradiation of the photosensitizers resulted in a potent antibacterial effect against S. aureus, E. coli, and even MRSA, which demonstrates the synergistic antibacterial efficacy of photodynamic therapy and chemotherapy.

Enhanced Efficacy of Gefitinib in Drug-Sensitive and Drug-Resistant Cancer Cell Lines after Arming with a Singlet Oxygen Releasing Moiety.

Attractive results have been achieved with small-molecule target-based drugs in the anticancer field; however, enhancing their treatment effect and solving the problem of drug resistance remain key concerns worldwide. Inspired by the specific affinity of gefitinib for tumour cells and the strong oxidation capacity of singlet oxygen, we combined a chemically generated singlet oxygen moiety with the small-molecule targeted drug gefitinib to improve its anticancer effect. We designed and synthesised a novel compound (Y5-1), in which a small-molecule targeted therapy agent (gefitinib) and a singlet oxygen (provided by an in vitro photodynamic reaction) thermally controlled releasing moiety are covalently conjugated. We demonstrated that the introduction of the singlet oxygen thermally controlled releasing moiety enhanced the anticancer activities of gefitinib. The results of this study are expected to provide a novel strategy to enhance the effect of chemotherapy drugs on drug-resistant cell lines.

Tumor Targeting Chemo- and Photodynamic Therapy Packaged in Albumin for Enhanced Anti-Tumor Efficacy.

PURPOSE: Combination therapy for tumors is an important and promising strategy to improve therapeutic efficiency. This study aims at combining tumor targeting, chemo-, and photodynamic therapies to improve the anti-tumor performance. PATIENTS AND METHODS: Human serum albumin (HSA), as a nontoxic and biodegradable drug carrier, was used to load hydrophobic photosensitizers (mono-substituted ß-4-pyridyloxy phthalocyanine zinc, mPPZ) by a dilution-incubation-purification (DIP) strategy to form molecular complex HSA:mPPZ. This complex was cross-linked as nanoparticles, and then chemotherapy drug doxorubicin (DOX) was adsorbed into the nanoparticles to achieve combined photodynamic therapy and chemotherapy. Next, the surface of the obtained composite was modified by a tumor surface receptor (urokinase receptor) targeting agent (ATF-HSA) using a noncovalent method to obtain the final product (ATF-HSA@HSA:mPPZ:DOX nanoparticles, AHmDN). RESULTS: AHmDN exhibited strong stability, remarkable cytotoxicity and higher uptake to tumor cells. Cell imaging analysis indicated that DOX was separated from AHmDN and uniformly distributed in cell nucleus while mPPZ localized in cytoplasm. The PDT activity of all the samples had been confirmed by the detection of intracellular ROS. In animal experiments, AHmDN was demonstrated to have a prominent tumor-targeting effect using a 3D imaging system. In addition, the enhanced antitumor effect of AHmDN in tumor-bearing mice was also been observed. Importantly, the tumor-targeting effect of such nanoparticles lasted for about 14 days after one injection. CONCLUSION: These albumin nanoparticles with combined functions of tumor targeting, chemotherapy and photodynamic therapy can highly enhance the anti-tumor effect. This drug delivery system can be applied to package other hydrophobic photosensitizers and chemotherapy drugs for improving therapeutic efficacy to tumors.

Small molecular target-based multifunctional upconversion nanocomposites for targeted and in-depth photodynamic and chemo-anticancer therapy.

A novel multifunctional nano-system, ZnPc-UCNPs-PEG-G, was designed for targeted and in-depth photodynamic therapy. The nano-system was built via covalent conjugation, in which phthalocyanine zinc (ZnPc), Gefitinib (G), NaYF4: Yb, Er (UCNPs) and PEG derivatives were employed as the photosensitizer, target moiety, upconversion nanomaterial and linker unit, respectively. The photophysical/chemical properties, in-depth photodynamic activity, cancer cell specificity and anticancer activity of ZnPc-UCNPs-PEG-G were investigated. The as-prepared ZnPc-UCNPs-PEG-G exhibits excellent photosensitizing ability, generating reactive oxygen species (ROS) via effective energy transfer from UCNP to phthalocyanine zinc. In addition, the composite exhibits specific affinity to HepG2 cancer cells and high anticancer activity. To the best of our knowledge, this is the only example of a UCNP platform that is capable of molecular targeted and in-depth photodynamic and chemo-anticancer therapy via the introduction of a small molecular targeting drug moiety.

An epidermal growth factor receptor-targeted and endoplasmic reticulum-localized organic photosensitizer toward photodynamic anticancer therapy.

The endoplasmic reticulum (ER), as the largest organelle in eukaryotic cells, plays complex but pivotal roles in multiple intracellular metabolic functions, including biosynthesis, sensing, and signal transduction, especially in proteins folding and post-translation modification. The ER is regarded as a promising target for anticancer therapy. Based on previous tumor-targeted photodynamic therapy (PDT), we chemically modified the phthalocyanine-based photosensitizer molecule with the small molecular anticancer-targeting drug erlotinib and the ER-targetable moiety methyl sulfonamide to develop an advanced photosensitizer EB-ER-Pc that can specifically target the subcellular organelle ER of EGFR-overexpressing cancer cells. The in vitro experiments show that the dual-target photosensitizer EB-ER-Pc can generate ROS in situ in the ER of the tumor target region to induce ER stress, upregulate Ca2+ ion level, and decrease mitochondrial membrane potential (MMP) to mediate cancer cells death and ablation. The results suggest that EB-ER-Pc is a promising candidate for effective photodynamic cancer therapy.

Epidermal Growth Factor Receptor-Targeted Delivery of a Singlet-Oxygen Sensitizer with Thermal Controlled Release for Efficient Anticancer Therapy.

Photodynamic therapy (PDT) utilizing light-induced singlet oxygen has achieved attractive results in anticancer fields; however, its development is hindered by limited light penetration depth, skin phototoxicity, tumor hypoxia, and PDT-induced hypoxia. Inspired by our previous research work and the limitations of PDT, we introduce a small-molecule-targeted drug erlotinib into the singlet-oxygen chemical source endoperoxide to achieve an EGFR-targeted PDT-mimetic sensitizer (Y3-1) for anticancer therapy. We demonstrated the erlotinib-based precise delivery of the singlet-oxygen chemical source (in vitro photosensitization) to EFGR-overexpressing tumor cells and tissues. Moreover, the anticancer assays validated that the enhanced anticancer efficacy (in vitro and in vivo) of Y3-1 was due to reversible singlet-oxygen thermal release. This study is expected to provide a smart strategy to break through the current roadblock in targeted PDT and achieve a more efficient anticancer therapy model.