Effect and Mechanism of a New Photodynamic Therapy with Glycoconjugated Fullerene

When irradiated, fullerene efficiently generates reactive oxygen species (ROS) and is an attractive photosensitizer for photodynamic therapy (PDT). Ideally, photosensitizers for PDT should be water-soluble and tumor-specific. Because cancer cells endocytose glucose more effectively than normal cells, the characteristics of fullerene as a photosensitizer were improved by combining it with glucose. The cytotoxicity of PDT was studied in several cancer cell lines cultured with C₆₀-(Glc)1 (d -glucose residue pendant fullerene) and C₆₀-(6Glc)1 (a maltohexaose residue pendant fullerene) subsequently irradiated with UVA₁. PDT alone induced significant cytotoxicity. In contrast, PDT with the glycoconjugated fullerene exhibited no significant cytotoxicity against normal fibroblasts, indicating that PDT with these compounds targeted cancer cells. To investigate whether the effects of PDT with glycoconjugated fullerene were because of the generation of singlet oxygen (¹O₂), NaN₃ was added to cancer cells during irradiation. NaN₃ extensively blocked PDT-induced apoptosis, suggesting that PDT-induced cell death was a result of the generation of ¹O₂. Finally, to investigate the effect of PDT in vivo, melanoma-bearing mice were injected intratumorally with C₆₀-(Glc)1 and irradiated with UVA₁. PDT with C₆₀-(Glc)1 suppressed tumor growth. These findings indicate that PDT with glycoconjugated fullerene exhibits tumor-specific cytotoxicity both in vivo and in vitro via the induction of ¹O₂.     

Self-Amplified Photodynamic Therapy through the 1O2-Mediated Internalization of Photosensitizers from a Ppa-Bearing Block Copolymer

Nanocarriers are employed to deliver photosensitizers for photodynamic therapy (PDT) through the enhanced penetration and retention effect, but disadvantages including the premature leakage and non-selective release of photosensitizers still exist. Herein, we report a ¹O₂-responsive block copolymer (POEGMA-b-P(MAA-co-VSPpaMA) to enhance PDT via the controllable release of photosensitizers. Once nanoparticles formed by the block copolymer have accumulated in a tumor and have been taken up by cancer cells, pyropheophorbide a (Ppa) could be controllably released by singlet oxygen (¹O₂) generated by light irradiation, enhancing the photosensitization. This was demonstrated by confocal laser scanning microscopy and in vivo fluorescence imaging. The ¹O₂-responsiveness of POEGMA-b-P(MAA-co-VSPpaMA) block copolymer enabled the realization of self-amplified photodynamic therapy by the regulation of Ppa release using NIR illumination. This may provide a new insight into the design of precise PDT.     

Self‐Amplified Photodynamic Therapy through the 1O2‐Mediated Internalization of Photosensitizers from a Ppa‐Bearing Block Copolymer

Nanocarriers are employed to deliver photosensitizers for photodynamic therapy (PDT) through the enhanced penetration and retention effect, but disadvantages including the premature leakage and non‐selective release of photosensitizers still exist. Herein, we report a ¹O₂‐responsive block copolymer (POEGMA‐b‐P(MAA‐co‐VSPpaMA) to enhance PDT via the controllable release of photosensitizers. Once nanoparticles formed by the block copolymer have accumulated in a tumor and have been taken up by cancer cells, pyropheophorbide a (Ppa) could be controllably released by singlet oxygen (¹O₂) generated by light irradiation, enhancing the photosensitization. This was demonstrated by confocal laser scanning microscopy and in vivo fluorescence imaging. The ¹O₂‐responsiveness of POEGMA‐b‐P(MAA‐co‐VSPpaMA) block copolymer enabled the realization of self‐amplified photodynamic therapy by the regulation of Ppa release using NIR illumination. This may provide a new insight into the design of precise PDT.     

AIE-active luminogens as highly efficient free-radical ROS photogenerator for image-guided photodynamic therapy

Image-guided photodynamic therapy (PDT) can realize highly precise and effective therapy via the integration of imaging and therapy, and has created high requirements for photosensitizers. However, the PDT modality usually utilizes conventional type II photosensitizers, resulting in unsatisfactory imaging and therapeutic outcomes due to aggregation-caused quenching (ACQ), “always on” fluorescence and strong oxygen dependence. Herein, we report the type I-based aggregation-induced emission (AIE) photosensitizer TCM-CPS with low oxygen dependence, near-infrared (NIR) emission and “off–on” fluorescence; in particular, it produces more reactive oxygen species (ROS) than commercially available Chlorin e6 and Rose Bengal. In the rational design of the AIE-based photosensitizer TCM-CPS, the strongly electron-donating carbazole unit and π-thiophene bridge distinctly extend the emission wavelength and decrease the autofluorescence interference in bio-imaging, and the hydrophilic pyridinium salt group guarantees good molecular dispersion and maintains the fluorescence-off state in the aqueous system to decrease the initial fluorescence background. Moreover, the strong donor–π–acceptor (D–π–A) character in TCM-CPS greatly separates the HOMO–LUMO distribution, enhancing the ROS generation, and TCM-CPS was constructed as a type I photosensitizer with the assistance of strong intramolecular charge transfer in the electron-rich anion–π⁺ structure. Based on its favorable hydrophilicity and photosensitivity, TCM-CPS was found to be a highly efficient free-radical ROS photogenerator for both visualizing cells using light-up NIR fluorescence and efficiently killing cancer cells upon light irradiation. The positively charged TCM-CPS could quickly bind to bacteria via electrostatic interactions to provide a light-up signal and kill bacteria at a low concentration. In the PDT treatment of bacteria-infected mice, the mice exhibited accelerated wound healing with low wound infection. Thus, the AIE-based type I photosensitizer TCM-CPS has great potential to replace commercially available photosensitizers in the image-guided PDT modality for the treatment of cancer and bacterial infection.

The AIE-based type I photosensitizer TCM-CPS exhibits high free radical generation and light-up fluorescence characteristics, giving it great potential in the image-guided PDT modality for the treatment of cancer and bacterial infections.     

Rational design of iridium–porphyrin conjugates for novel synergistic photodynamic and photothermal therapy anticancer agents

Near-infrared (NIR) emitters are important probes for biomedical applications. Nanoparticles (NPs) incorporating mono- and tetranuclear iridium(iii) complexes attached to a porphyrin core have been synthesized. They possess deep-red absorbance, long-wavelength excitation (635 nm) and NIR emission (720 nm). TD-DFT calculations demonstrate that the iridium–porphyrin conjugates herein combine the respective advantages of small organic molecules and transition metal complexes as photosensitizers (PSs): (i) the conjugates retain the long-wavelength excitation and NIR emission of porphyrin itself; (ii) the conjugates possess highly effective intersystem crossing (ISC) to obtain a considerably more long-lived triplet photoexcited state. These photoexcited states do not have the usual radiative behavior of phosphorescent Ir(iii) complexes, and they play a very important role in promoting the singlet oxygen (¹O₂) and heat generation required for photodynamic therapy (PDT) and photothermal therapy (PTT). The tetranuclear 4-Ir NPs exhibit high ¹O₂ generation ability, outstanding photothermal conversion efficiency (49.5%), good biocompatibility, low half-maximal inhibitory concentration (IC₅₀) (0.057 μM), excellent photothermal imaging and synergistic PDT and PTT under 635 nm laser irradiation. To our knowledge this is the first example of iridium–porphyrin conjugates as PSs for photothermal imaging-guided synergistic PDT and PTT treatment in vivo.

Iridium–porphyrin conjugates assembled in nanoparticles are photosensitizers that exhibit excellent photothermal imaging and synergistic PDT and PTT in vivo.     

Photodynamic Therapy Efficacy Enhanced by Dynamics: The Role of Charge Transfer and Photostability in the Selection of Photosensitizers

Progress in the photodynamic therapy (PDT) of cancer should benefit from a rationale to predict the most efficient of a series of photosensitizers that strongly absorb light in the phototherapeutic window (650–800 nm) and efficiently generate reactive oxygen species (ROS=singlet oxygen and oxygen‐centered radicals). We show that the ratios between the triplet photosensitizer–O₂ interaction rate constant (k_D) and the photosensitizer decomposition rate constant (k_d), k_D/k_d, determine the relative photodynamic activities of photosensitizers against various cancer cells. The same efficacy trend is observed in vivo with DBA/2 mice bearing S91 melanoma tumors. The PDT efficacy intimately depends on the dynamics of photosensitizer–oxygen interactions: charge transfer to molecular oxygen with generation of both singlet oxygen and superoxide ion (high k_D) must be tempered by photostability (low k_d). These properties depend on the oxidation potential of the photosensitizer and are suitably combined in a new fluorinated sulfonamide bacteriochlorin, motivated by the rationale.     

Assessing the Applicability of Singlet Oxygen Photosensitizers in Leaf Studies

Singlet oxygen (¹O₂) is of special interest in plant stress physiology. Studies focused on internal, chlorophyll‐mediated production are often complemented with the use of artificial ¹O₂ photosensitizers. Here, we report a comparative study on the effects of Rose Bengal (RB), Methylene Violet (MVI), Neutral Red (NR) and Indigo Carmine (IC). These were infiltrated into tobacco leaves at concentrations generating the same fluxes of ¹O₂ in solution. Following green light‐induced ¹O₂ production from these dyes, leaf photosynthesis was characterized by Photosystem (PS) II and PSI electron transport and oxidative damage was monitored as degradation of D1, a PSII core protein. Cellular localizations were identified on the basis of the dyes’ fluorescence using confocal laser scanning microscopy. We found that RB and NR were both localized in chloroplasts but the latter had very little effect, probably due to its pH‐dependent photosensitizing. Both RB and intracellular, nonplastid MVI decreased PSII electron transport, but the effect of RB was stronger than that of MVI and only RB was capable of damaging the D1 protein. Intercellularly localized IC had no significant effect. Our results also suggest caution when using RB as photosensitizer because it affects PSII electron transport.     

GSH and H2O2 Co‐Activatable Mitochondria‐Targeted Photodynamic Therapy under Normoxia and Hypoxia

Currently, photosensitizers (PSs) that are microenvironment responsive and hypoxia active are scarcely available and urgently desired for antitumor photodynamic therapy (PDT). Presented herein is the design of a redox stimuli activatable metal‐free photosensitizer (aPS), also functioning as a pre‐photosensitizer as it is converted to a PS by the mutual presence of glutathione (GSH) and hydrogen peroxide (H₂O₂) with high specificity on a basis of domino reactions on the benzothiadiazole ring. Superior to traditional PSs, the activated aPS contributed to efficient generation of reactive oxygen species including singlet oxygen and superoxide ion through both type 1 and type 2 pathways, alleviating the aerobic requirement for PDT. Equipped with a triphenylphosphine ligand for mitochondria targeting, ^mito aPS showed excellent phototoxicity to tumor cells with low light fluence under both normoxic and hypoxic conditions, after activation by intracellular GSH and H₂O₂. The ^mito aPS was also compatible to near infrared PDT with two photon excitation (800 nm) for extensive bioapplications.     

GSH and H2O2 Co-Activatable Mitochondria-Targeted Photodynamic Therapy under Normoxia and Hypoxia

Currently, photosensitizers (PSs) that are microenvironment responsive and hypoxia active are scarcely available and urgently desired for antitumor photodynamic therapy (PDT). Presented herein is the design of a redox stimuli activatable metal-free photosensitizer (aPS), also functioning as a pre-photosensitizer as it is converted to a PS by the mutual presence of glutathione (GSH) and hydrogen peroxide (H₂O₂) with high specificity on a basis of domino reactions on the benzothiadiazole ring. Superior to traditional PSs, the activated aPS contributed to efficient generation of reactive oxygen species including singlet oxygen and superoxide ion through both type 1 and type 2 pathways, alleviating the aerobic requirement for PDT. Equipped with a triphenylphosphine ligand for mitochondria targeting, ^mito aPS showed excellent phototoxicity to tumor cells with low light fluence under both normoxic and hypoxic conditions, after activation by intracellular GSH and H₂O₂. The ^mito aPS was also compatible to near infrared PDT with two photon excitation (800 nm) for extensive bioapplications.     

Doubly N‐Confused Calix[6]phyrin Bis‐Organopalladium Complexes: Photostable Triplet Sensitizers for Singlet Oxygen Generation

Triplet photosensitizers that generate singlet oxygen efficiently are attractive for applications such as photodynamic therapy (PDT). Extending the absorption band to a near‐infrared (NIR) region (700 nm≈) with reasonable photostability is one of the major demands in the rational design of such sensitizers. We herein prepared a series of mono‐ and bis‐palladium complexes ( 1‐Pd‐H₂ , 2‐Pd‐H₂ , 1‐Pd‐Pd , and 2‐Pd‐Pd ) based on modified calix[6]phyrins as photosensitizers for singlet oxygen generation. These palladium complexes showed intense absorption profiles in the visible‐to‐NIR region (500–750 nm) depending on the number of central metals. Upon photoirradiation in the presence of 1,5‐dihydroxynaphthalene (DHN) as a substrate for reactive oxygen species, the bis‐palladium complexes generated singlet oxygen with high efficiency and excellent photostability. Singlet oxygen generation was confirmed from the characteristic spectral feature of the spin trapped complex in the EPR spectrum and the intact ¹O₂ emission at 1270 nm.     

Synthesis and Photochemical Evaluation of Iodinated Squarylium Cyanine Dyes

Several (multiply) iodinated squarylium cyanine dyes of type 1 and 8 (see Scheme and Table), derived from 1,3‐benzothiazole and 6‐iodo‐1,3‐benzothiazole, were synthesized as potential new photosensitizers, with absorptions in the 700‐nm region. Their ability to generate singlet oxygen (¹O₂) was assessed by luminescence‐decay measurement in the near‐IR. Some of these new dyes show interesting photophysical properties, and may be potentially used in photodynamic therapy (PDT).     

Emodin-Based Nanoarchitectonics with Giant Two-Photon Absorption for Enhanced Photodynamic Therapy

Two-photon-excited photodynamic therapy (TPE-PDT) has significant advantages over conventional photodynamic therapy (PDT). However, obtaining easily accessible TPE photosensitizers (PSs) with high efficiency remains a challenge. Herein, we demonstrate that emodin (Emo), a natural anthraquinone (NA) derivative, is a promising TPE PS with a large two-photon absorption cross-section (TPAC: 380.9 GM) and high singlet oxygen (¹O₂) quantum yield (31.9 %). When co-assembled with human serum albumin (HSA), the formed Emo/HSA nanoparticles (E/H NPs) possess a giant TPAC (4.02×10⁷ GM) and desirable ¹O₂ generation capability, thus showing outstanding TPE-PDT properties against cancer cells. In vivo experiments reveal that E/H NPs exhibit improved retention time in tumors and can ablate tumors at an ultra-low dosage (0.2 mg/kg) under an 800 nm femtosecond pulsed laser irradiation. This work is beneficial for the use of natural extracts NAs for high-efficiency TPE-PDT.     

Gadolinium(III) Porpholactones as Efficient and Robust Singlet Oxygen Photosensitizers

Construction of Gd^III photosensitizers is important for designing theranostic agents owing to the unique properties arising from seven unpaired f electrons of the Gd³⁺ ion. Combining these with the advantages of porpholactones with tunable NIR absorption, we herein report the synthesis of Gd^III complexes Gd‐1 – 4 ( 1 , porphyrin; 2 , porpholactone; 3 and 4 , cis‐ and trans‐porphodilactone, respectively) and investigated their function as singlet oxygen (¹O₂) photosensitizers. These Gd complexes displayed ¹O₂ quantum yields (Φ_Δs) from 0.64–0.99 with the order Gd‐1 < Gd‐2 < Gd‐3 < Gd‐4 . The gradually enhanced ¹O₂ sensitization after β‐oxazolone moiety replacement was ascribed to the narrowing of the energy gap (ΔE) between the lowest triplet states (T₁) of the ligand and the energy level of the ¹Δ_g→³Σ_g transition of ¹O₂. In particular, Gd‐4 is capable of excitation in the visible to NIR region (400–700 nm) with a quantum yield near unity. These Gd complexes were first demonstrated as efficient photosensitizers in photocatalysis such as oxidative C?H bond functionalization of secondary or tertiary amines, and the oxygenation of the natural product cholesterol. Finally, after glycosylation, these water‐soluble Gd complexes showed potential applications in photodynamic therapy (PDT) in HeLa cells. This work revealed that Gd^III complexes of “bioinspired” β‐modified porpholactones are efficient NIR photosensitizers and form a chemical basis to construct appealing photocatalysts and theranostic agents based on lanthanides.     

A pH-activatable and aniline-substituted photosensitizer for near-infrared cancer theranostics

This work reports a newly designed pH-activatable and aniline-substituted aza-boron-dipyrromethene as a trifunctional photosensitizer to achieve highly selective tumor imaging, efficient photodynamic therapy (PDT) and therapeutic self-monitoring through encapsulation in a cRGD-functionalized nanomicelle. The diethylaminophenyl is introduced in to the structure for pH-activatable near-infrared fluorescence and singlet oxygen (¹O₂) generation, and bromophenyl is imported to increase the ¹O₂ generation efficiency upon pH activation by virtue of its heavy atom effect. After encapsulation, the nanoprobe can target α_vβ₃ integrin-rich tumor cells via cRGD and is activated by physiologically acidic pH for cancer discrimination and PDT. The fascinating advantage of the nanoprobe is near-infrared implementation beyond 800 nm, which significantly improves the imaging sensitivity and increases the penetration depth of the PDT. By monitoring the fluorescence decrease in the tumor region after PDT, the therapeutic efficacy is demonstrated in situ and in real time, which provides a valuable and convenient self-feedback function for PDT efficacy tracking. Therefore, this rationally designed and carefully engineered nanoprobe offers a new paradigm for precise tumor theranostics and may provide novel opportunities for future clinical cancer treatment.     

Studies on the Photodynamic Mechanism of Tetrapyrrole Compounds by Laser Flash Photolysis

Photodynamic therapy (PDT) is a promising new treatment technique which can potentially destroy unwanted and malignant tissues, such as those of cancer. The photodynamic mechanisms of three tetrapyrrole compounds: Mg‐purpurin‐18, tetra(meso‐chlorophenyl)porphyrin (m‐TCPP) and 2,7,12,18‐tetramethyl‐3,8‐di[(1‐isobutoxyl)‐ ethyl]‐13,17‐bis[3‐di(2‐chloroethyl)aminopropyl]porphyrin (TDBP) in acetonitrile were investigated by 355 nm laser flash photolysis. It was found that after laser flash photolysis (LFP), the excited states of TDBP and Mg‐purpurin‐18 could react with O₂ and ¹O₂ was produced, which proved that TDBP and Mg‐purpurin‐18 took effects through type II mechanism in PDT. This suggested that TDBP and Mg‐purpurin‐18 should be suitable for target tissues containing enough O₂. Mg‐purpurin‐18 has two extra absorptions at 550 and 700 nm, which means it has broad choices of laser wavelength in PDT. It was also found that m‐TCPP could be photoionized when excited with 355 nm laser under N₂‐saturated condition. It could also react with O₂ to produce reactive oxygen species such as superoxide and the peroxide anions, but not ¹O₂. These were known as the Type I mechanism. So m‐TCPP could be used even at low oxygen concentration or more polar environments with good behavior in PDT. From the above studies on the three different tetrapyrrole compounds it could be concluded that the structure of porphin ring takes a main role in PDT. And there was important impact on the photodynamic mechanism for the functional group directly connecting with porphin ring, while little influence for the functional group indirectly connecting with porphin ring. These will be of great value in the discovery of new PDT drugs.     

IONIC STRENGTH EFFECTS ON THE GROUND STATE COMPLEXATION and TRIPLET STATE ELECTRON TRANSFER REACTION BETWEEN ROSE BENGAL and METHYL VIOLOGEN

Abstract— The equilibrium constants, K_c, for complexation between methyl viologen dication (MV²+) and Rose Bengal, or Eosin Y, decrease with increasing ionic strength. At zero ionic strength K_c is 6500 (± 500) mol^?1 dm³ for Rose Bengal and 3200 (± 200) mol^?1 dm³ for Eosin Y, and these values decrease to 1500 (± 100) and 680 (± 40) mol^?1 dm³, respectively, at an ionic strength of 0.1 mol dm^?3. K_c is independent of pH between 4.5 and 10. ΔH is -25 (± 1) kJ mol^?1 for complexation with either dye, whereas ΔS is -15 (± 3) J K^?1 mol^?1 for Rose Bengal, and - 23 (± 3) J K^?1 mol^?1 for Eosin Y. The complexation constant for Rose Bengal and the neutral viologen, 4,4'-bipyridinium-N, N'-di(propylsulphonate), (4,4'-BPS), is 420 (± 35) mol^?1 dm³, and independent of ionic strength. No complexation could be observed for either Rose Bengal or Eosin with another neutral viologen, 2,2'-bipyridinium-N,N'-di(propylsulphonate), (2,2'-BPS). MV²+ quenches the triplet state of Rose Bengal with a rate constant of 7 × 10⁹ mol^?1 dm³ s^?1, and this rate constant decreases slightly as ionic strength increases. The cage escape yield following quenching, Φ_cc is very low (Φ_cc= 0.02 (± 0.005), and independent of ionic strength. 4,4'-BPS quenches the triplet state of Rose Bengal with a rate constant of 2.2 (± 0.1) × 10⁹ mol^?1 dm³ s^?1, and gives a cage escape yield of 0.033 (± 0.006). 2,2'-BPS quenches the Rose Bengal triplet with a rate constant of 6 (± 1) × 10⁸ mol^?1 dm³ s^?1 and gives a cage escape yield of 0.07 (± 0.01). Conductivity measurements indicate that MV²+(Cl^?)₂ is completely dissociated at concentrations below 2 × 10^?2 mol dm^?3.     

Metallophthalocyanine‐Based Conjugated Microporous Polymers as Highly Efficient Photosensitizers for Singlet Oxygen Generation

Singlet oxygen (¹O₂) is of great interest because of its potential applications in photodynamic therapy, photooxidation of toxic molecules, and photochemical synthesis. Herein, we report novel metallophthalocyanine (MPc) based conjugated microporous polymers (MPc‐CMPs) as photosensitizers for the generation of ¹O₂. The rigid microporous structure efficiently improves the exposure of the majority of the MPc units to oxygen. The MPc‐CMPs also exhibit an enhanced light‐harvesting capability in the far‐red region through their extended π‐conjugation systems. Their microporous structure and excellent absorption capability for long‐wavelength photons result in the MPc‐CMPs showing high efficiency for ¹O₂ generation upon irradiation with 700 nm light, as evident by using 1,3‐diphenylisobenzofuran as an ¹O₂ trap. These results indicate that MPc‐CMPs can be considered as promising photosensitizers for the generation of ¹O₂.     

ENHANCEMENT OF THE SENSITIVITY OF RADIATIVE and NON-RADIATIVE DETECTION TECHNIQUES IN THE STUDY OF PHOTOSENSITIZATION BY WATER SOLUBLE SENSITIZERS USING A REVERSE MICELLE SYSTEMS*,†

The study of photosensitization processes in aqueous solution is complicated by the unsuit-ability of water as solvent for the commonly used techniques for monitoring radiative and non-radiative relaxation processes. The infrared luminescence method is hampered by the relatively weak intensity of emission and short lifetime of singlet molecular oxygen, O₂(¹Δ_g), in water. Photoacoustic and photothermal detection of the dominant non-radiative relaxation process for O₂(¹Δ_g) is also inhibited by the unfavorable physico-chemical properties of water which reduce the sensitivities of these techniques for the study of sensitizers in aqueous with respect to non-aqueous media. Such problems have been alleviated by incorporating the sensitizer in the aqueous core of aerosol OT reverse micelles. It is demonstrated that the sensitivity of both radiative and non-radiative detection depends not on the local environment of the sensitizer but on the overall composition of the medium, which, in the case of reverse micelle solutions, is predominantly hydrocarbon. This produces a 4.5 and 6-fold enhancement of the sensitivity of luminescence and optoacoustic detection, respectively, in comparison to purely aqueous solution. The utility of the method is demonstrated for Rose Bengal, where quantum yields of intersystem crossing (φ_isc) of 0.78 (LIOAC) and singlet oxygen generation (φ_δ) of 0.81 (LIOAC) and 0.80 (TRLD) were measured. Phenazine was also studied for comparative purposes and to corroborate values obtained for Rose Bengal.     

Type I Photosensitizer Targeting G-Quadruplex RNA Elicits Augmented Immunity for Cancer Ablation

Type I photodynamic therapy (PDT) represents a promising treatment modality for tumors with intrinsic hypoxia. However, type I photosensitizers (PSs), especially ones with near infrared (NIR) absorption, are limited and their efficacy needs improvement via new targeting tactics. We develop a NIR type I PS by engineering acridinium derived donor-π-acceptor systems. The PS exhibits an exclusive type I PDT mechanism due to effective intersystem crossing and disfavored energy transfer to O₂, and shows selective binding to G-quadruplexes (G4s) via hydrogen bonds identified by a molecular docking study. Moreover, it enables fluorogenic detection of G4s and efficient O₂⋅⁻ production in hypoxic conditions, leading to immunogenic cell death and substantial variations of gene expression in RNA sequencing. Our strategy demonstrates augmented antitumor immunity for effective ablation of immunogenic cold tumor, highlighting its potential of RNA-targeted type I PDT in precision cancer therapy.     

Hypocrellin B doped and pH-responsive silica nanoparticles for photodynamic therapy

pH-responsive ¹O₂ photosensitizing systems may serve as selective photodynamic therapy (PDT) agents by targeting the acidic interstitial fluid of many kinds of tumors. In this work, a natural and clinically used photosensitizer (Hypocrellin B, HB) and a pH indicator (Bromocresol Purple, BCP) were co-encapsulated in organically modified silica nanoparticles. BCP successfully regulated the ¹O₂ generation efficiency of HB through the “inner filter” effect, which shows much stronger ¹O₂ generation ability in an acidic than in a basic environment. In vitro experiments also demonstrated that HB-doped nanoparticles are effective in killing tumor cells by PDT.