Singlet Oxygen Generation Efficiency Research Articles

Eosin Y derivatives for visible light-mediated free-radical polymerization: Applications in 3D-photoprinting and bacterial photodynamic inactivation

This study reports the design and the subsequent use of mono-allylated (EY-MA) and di-allylated (EY-DA) derivatives of eosin Y (EY) as highly efficient visible light-sensitive photosensitizers (PS) of bio-based H-donor molecules (cysteamine (Cys) or N-acetyl-L-cysteine (NAC)) and an electron donor (N-methyldiethanolamine, MDEA) for free-radical and thiol-acrylate polymerizations of a biobased monomer derived from soybean oil (SOA) upon exposure to visible light. High final acrylate conversions for SOA polymerization (up to 80 %) evidence the efficient photoinitiating properties of the eosin derivatives systems under irradiation with light emitting diodes (LEDs) centred at 405, 455 and 505 nm, and outperform those obtained with EY and other common photosensitizers such as camphorquinone or benzophenone. As described by fluorescence and phosphorescence analyses, laser flash photolysis (LFP) and electron paramagnetic resonance spin-trapping (EPR-ST) experiments, EY-MA and EY-DA can react via a proton/proton-coupled electron transfer reaction with Cys (or NAC) and MDEA respectively. The efficient singlet oxygen generation of the EY-MA-based materials upon exposure to visible light leads to excellent antibacterial properties, against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli). A 3-log decrease of E. coli adhesion on the surface of the materials is observed and 100 % adhesion inhibition of S. aureus is also demonstrated. The co-polymerization of the eosin-derived PS with the polymer matrix ensures sustainable antibacterial properties against both bacteria strains upon visible light exposure as it prevents their leakage out of the polymer network. Finally, finely complex 3D structures are successfully obtained by a 3D-photoprinting technology with the investigated EY-MA-based formulation using LED@405 nm.

F127/chlorin e6-nanomicelles to enhance Ce6 solubility and PDT-efficacy mitigating lung metastasis in melanoma.

Photodynamic Therapy (PDT) is a promising paradigm for treating cancer, especially superficial cancers, including skin and oral cancers. However, the effectiveness of PDT is hindered by the hydrophobicity of photosensitizers. Here, chlorin e6 (Ce6), a hydrophobic photosensitizer, was loaded into pluronic F127 micelles to enhance solubility and improve tumor-specific targeting efficiency. The resulting Ce6@F127 Ms demonstrated a significant increase in solubility and singlet oxygen generation (SOG) efficiency in aqueous media compared to free Ce6. The confocal imaging and fluorescence-activated cell sorting (FACS) analysis confirmed the enhanced internalization rate of Ce6@F127 Ms in murine melanoma cell lines (B16F10) and human oral carcinoma cell lines (FaDu). Upon laser irradiation (666nm), the cellular phototoxicity of Ce6@F127 Ms against B16F10 and FaDu was approximately three times higher than the free Ce6 treatment. The in vivo therapeutic investigations conducted on a murine model of skin cancer demonstrated the ability of Ce6@F127 Ms, when combined with laser treatment, to penetrate solid tumors effectively, which resulted in a significant reduction in tumor volume compared to free Ce6. Further, the Ce6@F127 Ms demonstrated upregulation of TUNEL-positive cells, downregulation of proliferation markers in tumor tissues, and prevention of lung metastasis with insignificant levels of proliferating cells and collagenase, as validated through immunohistochemistry. Subsequent analysis of serum and blood components affirmed the safety and efficacy of Ce6@F127 Ms in mice. Consequently, the developed Ce6@F127 Ms exhibits significant potential for concurrently treating solid tumors and preventing metastasis. The photodynamic formulation holds great clinical translation potential for treating superficial tumors.

Solvent-free oxidation of benzylic C(sp3)–H bond over MA3Bi2Br9 perovskite photocatalyst by efficient singlet oxygen generation

Photocatalytic selective oxidation under solvent-free conditions plays a pivotal role in green chemistry, which can diminish pollutant production and minimize resource consumption in chemical reactions. In this process, the activation of molecular oxygen (O2) plays a crucial role. Here, we demonstrate the efficient oxidation of C(sp3)–H bond in pure toluene to produce oxygenated products of benzaldehyde (BAD) and benzyl alcohol (BA) using O2 as an oxidant over lead-free MA3Bi2Br9 perovskite. Systematic spectroscopic characterizations and controlled experiments validate that MA3Bi2Br9 enables the activation of O2 to superoxide radical (•O2−) and singlet oxygen (1O2) via charged electron transfer and excitonic energy transfer, respectively. Significantly, 1O2 emerges as an important active species. The optimal photocatalytic performance delivered by MA3Bi2Br9 reaches a BAD generation rate of 10756 µmol g−1h−1, with a BAD product selectivity of 81.5 %. The performance is greater than most classical photocatalysts, representing one of the best photocatalytic activities available in the literature. The lead-free feature of MA3Bi2Br9 perovskite coupled with its impressive catalytic performance makes it promising for practical applications.

Combination of photodynamic therapy with antibiotic therapy - future or misalliance?

SignificanceThe growing antibiotic resistance of microorganisms is an increasingly important challenge for modern medicine. In the next few decades, the so-called post antibiotic era is likely to begin. For this reason, the search for new solutions using PACT seems particularly promising. ApproachFour new chlorin compounds were tested and photochemically characterized for singlet oxygen generation efficiency and photostability. They have been evaluated for bactericidal properties against MRSA, E. coli (ESBL+) and C. albicans. Their synergism with antibiotics from the group of cephalosporins and carbapenems was evaluated. ResultsA reduction of approximately 3 logs or more was achieved for each of the bacterial strains. A decrease in MIC values was observed for all bacteria, the greatest for ceftriaxone. ConclusionsCombining traditional antibiotic therapy with PACT may be a promising route in the case of antibiotic-resistant infections, but requires further in-depth research.

Modified Gold Nanoparticles Modulated Fluorescence and Singlet Oxygen Generation of Pheophorbide a as an Effective Platform for Photodynamic Therapy against Staphylococcus aureus

AbstractThe paper reports on the synthesis and evaluation of photochemical properties of gold nanorods (Au−NRs) coated with PEG with a thiol (−SH) group or SiO2 and their physical mixtures with pheophorbide a. Also biological activity of these systems was tested in photodynamic therapy directed towards Staphylococcus aureus. The potential additive effect between differently functionalized Au−NRs and the dye pheophorbide a was also studied. The efficiency of singlet oxygen generation varied considerably depending on the type of PEG polymer used for coating NRs and was the highest, of 65%, for the polymer PEG (10k) and the Au−NRs concentration of (1.33×10−11 M). For the other studied PEGs (2k, 5k) and the same concentration of NRs, a decrease in the singlet oxygen generation efficiency was observed. The most effective against Gram‐positive bacteria were the mixtures of PEG‐coated Au−NRs with pheophorbide a, exposed to irradiation at 405 nm and 660 nm, which provided a >5.8 log reduction in the bacteria growth. However, no strong bactericidal effect was noted in the case of irradiation with 525 nm.

Photogeneration and quenching of singlet molecular oxygen by bacterial C40 carotenoids with long chain of conjugated double bonds.

Measurement of photosensitized luminescence of singlet oxygen has been applied to studies of singlet oxygen generation and quenching by C40 carotenoids (neurosporene, lycopene, rhodopin, and spirilloxanthin) with long chain of conjugated double bonds (CDB) using hexafluorobenzene as a solvent. It has been found that neurosporene, lycopene, and rhodopin are capable of the low efficient singlet oxygen generation in aerated solutions upon photoexcitation in the spectral region of their main absorption maxima. The quantum yield of this process was estimated to be (1.5-3.0) × 10-2. This value is near the singlet oxygen yields in solutions of ζ-carotene (7 CDB) and phytoene (3 CDB) and many-fold smaller than in solutions of phytofluene (5 CDB) (Ashikhmin et al. Biochemistry (Mosc) 85:773-780, https://doi.org/10.1134/S0006297920070056 , 2020, Biochemistry (Mosc) 87:1169-1178, 2022, https://doi.org/10.1134/S00062979221001082022 ). Photogeneration of singlet oxygen was not observed in spirilloxanthin solutions. A correlation was found between the singlet oxygen yields and the quantum yields and lifetimes of the fluorescence of the carotenoid molecules. All carotenoids were shown to be strong physical quenchers of singlet oxygen. The rate constants of 1O2 quenching by the carotenoids with long chain of CDB (9-13) were close to the rate constant of the diffusion-limited reactions ≈1010M-1s-1, being many-fold greater than the rate constants of 1O2 quenching by the carotenoids with the short chain of CDB (3-7) phytoene, phytofluene, and ζ-carotene studied in prior papers of our group (Ashikhmin et al. 2020, 2022). To our knowledge, the quenching rate constants of rhodopin and spirilloxanthin have been obtained in this paper for the first time. The mechanisms of 1O2 photogeneration by carotenoids in solution and in the LH2 complexes of photosynthetic cells, as well as the efficiencies of their protective action are discussed.

BODIPY-fused uracil: synthesis, photophysical properties, and applications.

Fluorescent nucleobase and nucleic acid analogs are important tools in chemical and molecular biology as fluorescent labelling of nucleobases has applications in cellular imaging and anti-tumor activity. Boron-dipyrromethene (BODIPY) dyes exhibiting high brightness and good photostability are extensively used as fluorescent labelling agents and as type II photosensitizers for photodynamic therapy. Thus, the combination of nucleobases and BODIPY to obtain new compounds with both anti-tumor activity and fluorescent imaging functions is the focus of our research. We synthesized two new nucleobase analogs 1 and 2 by fusing the BODIPY core directly with uracil which resulted in favorable photophysical properties and high emission quantum efficiencies particularly in organic solvents. Further, we explored the newly synthesized derivatives, which possessed good singlet oxygen generation efficiencies and bio-compatibility, as potential PDT agents and our results show that they exhibit in vitro anti-tumor activities.

Red-light operable photosensitizer with symmetry-breaking charge transfer induced intersystem crossing for polymerization of methyl methacrylate.

We present a red light-activated zincII bis(dipyrrin) symmetry breaking charge transfer (SBCT) architecture, showing a large molar absorption coefficient (ε = 15.4 × 104 M-1 cm-1), high reactive singlet oxygen generation efficiency (ΦΔ ≈ 0.8) and long-lived triplet state (τT = 150 μs) compared to the donor-acceptor analogue dipyrrin-BF2 complex, highlighting the superiority of the SBCT approach. For the first time, we demonstrated the potential of a SBCT scaffold in red-light-induced methyl methacrylate (MMA) polymerization, using a dual photocatalyst excitation approach.

In-situ formation of Ni2P on black phosphorus surface for efficient NIR photocatalytic singlet oxygen generation

Black phosphorus (BP) shows great potential applications in photoelectric conversion and photocatalysis, but its applications are limited by its disadvantages such as poor ambient stability and rapid carrier recombination under photoirradiation. In this work, it was surprisingly found that the in-situ generation of Ni2P onto the surface of BP leaded to a significant improvement in both ambient stability and photocatalytic singlet oxygen (1O2) generation under NIR irradiation. Because of the transfer of electrons from Ni to BP via Ni-P bonds, the Ni2P/BP showed better charge separation efficiency and ambient stability in NIR photoelectric conversion. Moreover, the Ni2P/BP was able to generate 1O2 for NIR photocatalysis through Russell Mechanism. Meanwhile, norfloxacin and E. coli could also be removed by Ni2P/BP under NIR irradiation, which further shows the ability to generate 1O2 for practical utilization. This work provides a novel insight into the passivation of BP by hetero-atoms doping and a new strategy for green NIR photocatalytic water remediation.

Effect of meso-substituents and medium properties on the photo- and pH-stability, penetration efficiency into bacterial and microscopic fungi cells of terpene-BODIPY conjugates

In order to expand the arsenal of tools and areas for practical use of BODIPY dyes as bifunctional fluorescent theranostics, we studied the effect of the meso-substituents nature and medium properties on photo- and pH-stability, efficiency of singlet oxygen generation, and affinity to biostructures of terpene-BODIPY conjugates. The BODIPYs fused with myrtenol or thiotherpenoid via carboxylic acid residues exhibit high stability over a wide pH range and the presence of a bulky substituent at the meso-position of BODIPY conjugates increases their photostability two-fold compared to structurally related meso-unsubstituted analogues. Furthermore, the photodegradation rate of the conjugates directly depends on their ability to generate singlet oxygen and the course probability of the corresponding red-ox reactions involving reactive oxygen species. The conjugate of BODIPY with a thiotherpenoid demonstrated high ability to penetrate the membranes of filamentous and yeast-like fungi and bind to membrane of organelles in the fungal cell. At the same time, this compound also had a high ability to penetrate into biofilms of Staphylococcus aureus and Klebsiella pneumoniae and into bacterial cells within the matrix, which makes this compound promising for staining intracellular structures of eukaryotic cells and bacteria embedded into biofilms.

Photodynamic Eradication of Pseudomonas aeruginosa with Ru-Photosensitizers Encapsulated in Enzyme Degradable Nanocarriers.

The development of new approaches for the treatment of the increasingly antibiotic-resistant pathogen Pseudomonas aeruginosa was targeted by enhancing the effect of local antimicrobial photodynamic therapy (aPDT) using poly(ethylene glycol)-block-poly(lactic acid) (PEG114-block-PLAx) nanocarriers that were loaded with a ruthenium-based photosensitizer (PS). The action of tris(1,10-phenanthroline) ruthenium (II) bis(hexafluorophosphate) (RuPhen3) encapsulated in PEG114-block-PLAx micelles and vesicles was shown to result in an appreciable aPDT inactivation efficiency against planktonic Pseudomonas aeruginosa. In particular, the encapsulation of the PS, its release, and the efficiency of singlet oxygen (1O2) generation upon irradiation with blue light were studied spectroscopically. The antimicrobial effect was analyzed with two strains of Pseudomonas aeruginosa. Compared with PS-loaded micelles, formulations of the PS-loaded vesicles showed 10 times enhanced activity with a strong photodynamic inactivation effect of at least a 4.7 log reduction against both a Pseudomonas aeruginosa lab strain and a clinical isolate collected from the lung of a cystic fibrosis (CF) patient. This work lays the foundation for the targeted eradication of Pseudomonas aeruginosa using aPDT in various medical application areas.

Singlet oxygen generation efficiency and antimicrobial ability in glutathione protected Ag31 nanoclusters

Ligand protected silver nanoclusters (Ag NCs) have recently been reported to have significant applications as antimicrobial agents. In the current study, glutathione (SG) protected silver nanocluster was synthesized leading to Ag31SG19 by cyclic reduction and oxidative condition and was evaluated for its singlet oxygen generation and antibacterial activity. From the results of the study, Ag31SG19 was found to have inhibitory activity against Escherichia coli and Staphylococcus aureus with a diameter of 15.30 ± 0.58 mm and 16.70 ± 0.58 mm respectively. The Minimum Inhibitory Concentration was also calculated to have 0.3125 mg/ml and 0.1562 mg/ml respectively. In addition, the Ag31SG19 was found to have high efficiency for the generation of singlet oxygen. Based on the results of the study, the antimicrobial mechanisms of Ag31SG19 could be predicted to be mainly because of the generation of singlet oxygen species in addition to the activity due to the release of Ag+ ions from the nanoclusters. These multimechanistic antimicrobial effects make the synthesized Ag31SG19 to be a promising candidate for a broad range of antimicrobial applications.

Efficient Singlet Oxygen Generation via ZIF67@CNT Three-Dimensional Electrodes for Highly Effective Decomposition of Polycyclic Aromatic Hydrocarbon with Low Energy Consumption

Efficient Singlet Oxygen Generation via ZIF67@CNT Three-Dimensional Electrodes for Highly Effective Decomposition of Polycyclic Aromatic Hydrocarbon with Low Energy Consumption

Imidazolium-Based Heavy-Atom-Free Photosensitizer for Nucleus-Targeted Fluorescence Bioimaging and Photodynamic Therapy.

The development of heavy-atom-free photosensitizers (PSs) for photodynamic therapy (PDT) has encountered significant challenges in achieving simultaneous high fluorescence emission and reactive oxygen species (ROS) generation. Moreover, the limited water solubility of these PSs imposes further limitations on their biomedical applications. To overcome these obstacles, this study presents a molecular design strategy employing hydrophilic heavy-atom-free PSs based on imidazolium salts. The photophysical properties of these PSs were comprehensively investigated through a combination of experimental and theoretical analyses. Notably, among the synthesized PSs, the ethylcarbazole-naphthoimidazolium (NI-Cz) conjugate exhibited efficient fluorescence emission (ΦF = 0.22) and generation of singlet oxygen (ΦΔ = 0.49), even in highly aqueous environments. The performance of NI-Cz was validated through its application in fluorescence bioimaging and PDT treatment in HeLa cells. Furthermore, NI-Cz holds promise for two-photon excitation and type I ROS generation, nucleus localization, and selective activity against Gram-positive bacteria, thereby expanding its scope for the design of heavy-atom-free PSs and phototheranostic applications.

A dipyridophenazine Ni(II) dithiolene complex as a dual-acting cancer phototherapy agent activatable within the phototherapeutic window

A combination of photodynamic therapy (PDT) and photothermal therapy (PTT) within the phototherapeutic window (600–900 nm) can lead to significantly enhanced therapeutic outcomes, surpassing the efficacy observed with PDT or PTT alone in cancer phototherapy. Herein, we report a novel small-molecule mixed-ligand Ni(II)-dithiolene complex (Ni-TDD) with a dipyridophenazine ligand, demonstrating potent red-light PDT and significant near-infrared (NIR) light mild-temperature PTT activity against cancer cells and 3D multicellular tumour spheroids (MCTSs). The four-coordinate square planar complex exhibited a moderately intense absorption band (ε ∼ 3700 M−1cm−1) centered around 900 nm and demonstrated excellent dark and photostability in an aqueous phase. Ni-TDD induced a potent red-light (600–720 nm) PDT effect on HeLa cancer cells (IC50 = 1.8 μM, photo irritation factor = 44), triggering apoptotic cell death through efficient singlet oxygen generation. Ni-TDD showed a significant intercalative binding affinity towards double-helical calf thymus DNA, resulting in a binding constant (Kb) ∼ 106 M−1. The complex induced mild hyperthermia and exerted a significant mild-temperature PTT effect on MDA-MB-231 cancer cells upon irradiation with 808 nm NIR light. Simultaneous irradiation of Ni-TDD-treated HeLa MCTSs with red and NIR light led to a remarkable synergistic inhibition of growth, exceeding the effects of individual irradiation, through the generation of singlet oxygen and mild hyperthermia. Ni-TDD displayed minimal toxicity towards non-cancerous HPL1D and L929 cells, even at high micromolar concentrations. This is the first report of a Ni(II) complex demonstrating red-light PDT activity and the first example of a first-row transition metal complex exhibiting combined PDT and PTT effects within the clinically relevant phototherapeutic window. Our findings pave the way for designing and developing metal-dithiolene complexes as dual-acting cancer phototherapy agents using long wavelength light for treating solid tumors.

Cyclometalated Ir(III) Complexes as Lysosome-Targeted Photodynamic Anticancer Agents.

We have designed and synthesized two Ir(III) complexes (Ir1 and Ir2) coordinated with an 8-sulfonamidoquinoline derivative ligand as photosensitizers, which exhibit strong red phosphorescence emission and a long phosphorescence lifetime. The Ir(III) complexes exhibit a high population of triplet states, which enable red phosphorescence and efficient singlet oxygen generation. Ir1 and Ir2 rapidly enter the cancer cells and accumulate in lysosomes, producing large amounts of intracellular singlet oxygen when exposed to light irradiation, eventually leading to cancer cell death, and the phototoxic indexes of complexes Ir1 and Ir2 against cancer cells are in the range of 76-228. Overall, our studies indicate that the synthesized Ir(III) complexes with quinoline ligands exhibit photosensitizing properties, effectively inducing cancer cell death when exposed to light. These promising results suggest their potential application in photodynamic therapy.

Aza-BODIPY dye with unexpected bromination and high singlet oxygen quantum yield for photoacoustic imaging-guided synergetic photodynamic/photothermal therapy

Introducing heavy halogen atoms into organic small molecules is a practical strategy for efficient singlet oxygen (1O2) generation. Generally, bromine or iodine atoms are introduced on the aza-boron-dipyrromethene (aza-BODIPY) core, rather than on the periphery aryl rings for efficient 1O2 generation. Herein, an aza-BODIPY dye NBDPBr with unexpected bromination on the periphery aryl rings was synthesized for photoacoustic (PA) imaging-guided synergistic photothermal therapy (PTT) and photodynamic therapy (PDT) in tumor cells. Owing to unexcepted bromination at the periphery aryl rings, NBDPBr demonstrated an outstanding singlet oxygen quantum yield (ΦΔ) of 66% which was superior to similar brominated photosensitizers previously reported. After encapsulation with amphiphilic polymer F-127, hydrophilic NBDPBr nanoparticles (NPs) were fabricated and exhibited an excellent photothermal conversion efficiency (η) of 43.0% under 660 nm photoirradiation. In vivo PA imaging results demonstrated that NBDPBr NPs could specifically accumulate at tumor sites and realized the maximum tumor retention at 7 h post-injection. All the in vitro and in vivo results indicated the significant potence of NBDPBr with unexpected bis-bromination for PA imaging-guided synergetic PDT/PTT.

Spectroscopic study of methylene blue photophysical properties in biological media

A spectroscopic study of the photophysical properties of methylene blue (MB) in aqueous solutions was carried out. Absorption and fluorescence spectra as well as fluorescence lifetime were recorded. The concentration dependence of the intensity and shape of the spectra allowed establishing the ranges of MB concentrations for in vitro and in vivo studies at which aggregation is not observed (up to 0.01 mM, which corresponds to 3.2 mg/kg). Studies of photodegradation in biological media showed that photobleaching of more than 80% in plasma and culture media is observed already at a dose of 5 J/cm2 , while in water at this concentration and dose photobleaching is not yet observed, and at a dose of 50 J/cm2 photobleaching of MB is about 30%. It was found that in media containing proteins and having an alkaline pH, photobleaching occurs significantly faster than in neutral aqueous media. The ionic strength of the solution has no effect on the photobleaching rate. Such photobleaching is caused by the photodegradation of MB rather than the transition to the leucoform.The efficiency of singlet oxygen generation and photodynamic activity were evaluated in vitro. In the investigated range of MB concentrations, the efficiency of singlet oxygen generation is rather low, because positively charged MB binds to negatively charged cell membranes, which leads to a change in the type of photodynamic reaction. The emergence of other reactive oxygen species (ROS), different from singlet oxygen, in cells has been demonstrated. The generation of ROS and the low quantum yield of singlet oxygen generation indicate the tendency of MB to provide the type I photosensitization mechanism (electron transfer with the formation of semi-reduced and semi-oxidized MB+ radicals) rather than to the type II mechanism (energy transfer to oxygen with the formation of singlet oxygen) in biological media and in vivo.

Photocatalytic Degradation of Water Pollutants and Pesticides Using Plasmon‐Molecule Coupled Gold‐BODIPY Nanoparticles

AbstractDevelopment of effective and sustainable water treatment processes is the need‐of‐the‐hour for addressing the global water crisis. Here, we report the synthesis of a plasmon‐molecule coupled nanocomposite (NC) and its photosensitization properties in solution and on thin films. Our results indicate that the thin films exhibit excellent stability at different temperatures and pH conditions and that the plasmonic photoexcitations result in efficient generation of singlet oxygen. The thin film serves as a heterogeneous photocatalyst for the degradation of a variety of water pollutants and pesticides. This approach thus offers a low‐cost, environmental friendly and singlet oxygen mediated photocatalytic solution for degrading organic contaminants.

Macrophage-reprogramming upconverting nanoparticles for enhanced TAM-mediated antitumor therapy of hypoxic breast cancer

In an attempt to achieve antitumor effects by switching the phenotype of macrophages from the tumor-promoting M2 type to the tumor-suppressing M1 type, we fabricated mannose-decorated/macrophage membrane–coated, silica-layered NaErF4@NaLuF4 upconverting nanoparticles (UCNPs) co-doped with perfluorocarbon (PFC)/chlorin e6 (Ce6) and loaded with paclitaxel (PTX) (UCNP@mSiO2-PFC/Ce6@RAW-Man/PTX: ∼61 nm; −11.6 mV). These nanoparticles were designed to have two major functionalities, (i) efficient singlet oxygen generation aided by an oxygen supply and (ii) good targeting to tumor-associated macrophage (TAMs) (M2-type), to induce polarization to M1 type macrophages that release proinflammatory cytokines and suppress breast cancers. The primary UCNPs consisted of lanthanide elements (erbium and lutetium) in a core@shell structure, and they facilely emitted 660 nm light in response to a deep-penetrating 808 nm near-infrared laser. Moreover, the UCNPs@mSiO2-PFC/Ce6@RAW-Man/PTX were able to release O2 and generate 1O2 because of the co-doped PFC/Ce6 and upconversion. Our nanocarriers' excellent uptake to RAW 264.7 macrophage cells (M2 type) and efficient M1-type polarization activity were clearly demonstrated using qRT-PCR and immunofluorescence-based confocal laser scanning microscopy. Our nanocarriers displayed significant cytotoxicity to 4T1 cells in 2D culture and 3D co-culture systems of 4T1/RAW 264.7 cells. More importantly, UCNPs@mSiO2-PFC/Ce6@RAW-Man/PTX (+808 nm laser) noticeably suppressed tumor growth in 4T1-xenografted mice, compared with the other treatment groups (332.4 vs. 709.5–1185.5 mm3). We attribute this antitumor efficacy to the prominent M1-type macrophage polarization caused by our nanocarriers through efficient ROS/O2 generation and targeting of M2-type TAMs via mannose ligands on coated macrophage-membrane.