In Vitro Photoselective Gene Transfection of Hepatocellular Carcinoma Cells with Hypericin Lipopolyplexes.

The lipopolyplex, a multicomponent nonviral gene carrier, generally demonstrates superior colloidal stability, reduced cytotoxicity, and high transfection efficiency. In this study, a new concept, photochemical reaction-induced transfection, using photosensitizer (PS)-loaded lipopolyplexes was applied, which led to enhanced transfection and cytotoxic effects by photoexcitation of the photosensitizer. Hypericin, a hydrophobic photosensitizer, was encapsulated in the lipid bilayer of liposomes. The preformed nanosized hypericin liposomes enclosed the linear polyethylenimine (lPEI)/pDNA polyplexes, resulting in the formation of hypericin lipopolyplexes (Hy-LPP). The diameters of Hy-LPP containing 50 nM hypericin and 0.25 µg of pDNA were 185.6 ± 7.74 nm and 230.2 ± 4.60 nm, respectively, measured by dynamic light scattering (DLS) and atomic force microscopy (AFM). Gel electrophoresis confirmed the encapsulation of hypericin and pDNA in lipopolyplexes. Furthermore, in vitro irradiation of intracellular Hy-LPP at radiant exposures of 200, 600, and 1000 mJ/cm2 was evaluated. It demonstrated 60- to 75-fold higher in vitro luciferase expression than that in nonirradiated cells. The lactate dehydrogenase (LDH) assay supported that reduced transfection was a consequence of photocytotoxicity. The developed photosensitizer-loaded lipopolyplexes improved the transfection efficiency of an exogenous gene or induced photocytotoxicity; however, the frontier lies in the applied photochemical dose. The light-triggered photoexcitation of intracellular hypericin resulted in the generation of reactive oxygen species (ROS), leading to photoselective transfection in HepG2 cells. It was concluded that the two codelivered therapeutics resulted in enhanced transfection and a photodynamic effect by tuning the applied photochemical dose.

Potential-Resolved Ratio Electrochemiluminescence Biosensor Based on Perylene Diimide-MOF and DNA Nanoflowers-CdS Quantum Dots for Detection of Dual Targets.

BRCA1 gene and carcinoembryonic antigen (CEA) are important markers of breast cancer, so accurate detection of them is significant for early detection and diagnosis of breast cancer. In this study, a potential-resolved ratio electrochemiluminescence (ECL) biosensor using perylene diimide (PDI)-metal-organic framework and DNA nanoflowers (NFs)-CdS quantum dots (QDs) was constructed for detection of BRCA1 and CEA. Specifically, PDI-MOF and CdS QDs can generate potential-resolved intense ECL signals only using one coreactant, so the detection procedure can be effectively simplified. PDI-MOF was first attached to the electrode by graphene oxide, and the dopamine (DA) probe was linked to quench the ECL signal by DNA hybridization. In the presence of target BRCA1, it can form a bipedal DNA walker, so the quenching molecules (DA) were detached from the electrode via the walker amplification process aided by Mg2+, so that the PDI signal at -0.25 V was restored for the BRCA1 assay. Moreover, CdS QDs@DNA NFs as amplified signal probes were formed by self-assembly, and the target CEA-amplified product introduced the CdS QDs@DNA NFs to the electrode, so the QD ECL signal at -1.42 V was enhanced, while the ECL signal of PDI is unchanged; thus, CEA detection was achieved by the ratio value between them. Therefore, the detection accuracy is guaranteed by detection of two cancer markers and a ratio value. This biosensor has a great contribution to the development of new ECL materials and a novel ECL technique for fast and efficient multitarget assays, showing great significance for the early monitoring and diagnosis of breast cancer.

Heparin binding induced supramolecular chirality into the self-assembly of perylenediimide bolaamphiphile.

Chirality is one of the hallmarks of biomolecules. Herein, we utilize heparin, a chiral biomolecule and potent drug, to induce chiral organization into the assembly of an achiral molecule. Polyanionic heparin binds with a dicationic perylenediimide derivative to induce supramolecular helical organization in aqueous medium as well as in a highly competitive cell culture medium.

Bipolar electrochemical sensor with perylene diimide-based cathodic luminophore for dopamine detection and imaging.

Bipolar electrochemical microscopy (BEM), which visualizes the concentration distribution of molecular species in biological systems by electrochemiluminescence (ECL), is expected to be applied to the high-spatiotemporal-resolution imaging of biomolecules, enabling the analysis of cellular functions. In the past, the molecular species that could be imaged by BEM were generally restricted to oxidized molecules due to the limitation derived from the ECL mechanism of the luminophore. Recently, the imaging of dopamine (DA), a reduced molecule, was achieved using Ru (bpy)32+/glutathione disulfide (GSSG) as a cathodic luminophore. However, a large driving voltage was required for ECL generation, resulting in a low S/N ratio. In this study, we employed N,N'-dimethyl-3,4,9,10-perylenetetracarboxylic diimide (PDI-CH3)/potassium peroxodisulfate (K2S2O8), which is a cathodic luminophore that can be reduced at a nobler potential to produce ECL than [Ru(bpy)3]2+/GSSG. First, the ECL mechanism of PDI-CH3/K2S2O8 was elucidated by using a PDI-CH3 drop-cast glassy carbon electrode (GCE) immersed in K2S2O8 solution as the working electrode in a 3-electrode system. The PDI-CH3 drop-casted GCE, a single closed bipolar electrode (c-BPE), was used as the cathode in the successful quantification of 50-500 µmol L-1 DA in a sample chamber in which a c-BPE anode was immersed, resulting in a high S/N. The selective detection of DA in the presence of ascorbic acid was achieved by modifying the anode with Nafion. Finally, DA imaging was demonstrated using a commercially available anisotropic conducting film with PDI-CH3 coating on the cathode surface as a c-BPE array. The change in the concentration distribution in the inflow of DA was successfully imaged based on the change in the ECL intensity at the c-BPE cathode. This BEM system is expected to be useful for DA imaging of the brain.

Controlled Release of Curcumin and Hypocrellin A from Electrospun Poly(l-Lactic Acid)/Silk Fibroin Nanofibers for Enhanced Cancer Cell Inhibition.

Nanofibers have emerged as a highly effective method for drug delivery, attributed to their remarkable porosity and ability to regulate drug release rates while minimizing toxicity and side effects. In this study, we successfully loaded the natural anticancer drugs curcumin (CUR) and hypocrellin A (HA) into pure poly(l-lactic acid) (PLLA) and PLLA-silk protein (PS) composite nanofibers through electrospinning technology. This result was confirmed through comprehensive analysis involving SEM, FTIR, XRD, DSC, TG, zeta potential, and pH stability analysis. The encapsulation efficiency of all samples exceeded 85%, demonstrating the effectiveness of the loading process. Additionally, the drug release doses were significantly higher in the composites compared to pure PLLA, owing to the enhanced crystallinity and stability of the silk proteins. Importantly, the composite nanofibers exhibited excellent pH stability in physiological and acidic environments. Furthermore, the drug-loaded composite nanofibers displayed strong inhibitory effects on cancer cells, with approximately 28% (HA) and 37% (CUR) inhibition of cell growth and differentiation within 72 h, while showing minimal impact on normal cells. This research highlights the potential for controlling drug release through the manipulation of fiber diameter and crystallinity, paving the way for wider applications of electrospun green nanomaterials in the field of medicine.

Construction and synergistic anti-tumor study of a tumor microenvironment-based multifunctional nano-drug delivery system.

To solve the problems existing in the clinical application of hypericin (Hyp) and tirapazamine (TPZ), a nano-drug delivery system with synergistic anti-tumor functions was constructed using mesoporous silica nanoparticles (MSN) and sodium alginate (SA). The system exhibited excellent stability, physiological compatibility and targeted drug release performance in tumor tissues. In the in vitro and in vivo experiments, Hyp released from MSN killed tumor cells through photodynamic therapy (PDT). The degree of hypoxia in the tumor tissue site was exacerbated, enabling TPZ to fully exert its anti-tumor activity. Our studies suggested that the synergistic effects between the components of the nano-drug delivery system significantly improve the anti-tumor properties of Hyp and TPZ.

PBI derivatives/surfactant-based fluorescent ensembles: Sensing of multiple aminoglycoside antibiotics and interaction mechanism studies.

Fluorescent aggregates and ensembles have been widely applied in fabrication of fluorescent sensors due to their capacity of encapsulating fluorophores and modulating their photophysical properties. In the present work, fluorescent ensembles based on anionic surfactant SDS assemblies and perylene derivatives (PBIs) were particularly constructed. Three newly synthesized neutral PBI derivatives with different structures, PO, PC1 and PC2, were used for the purpose to evaluate probe structure influence on constructing fluorescent ensembles. The one with hydrophilic side chains, PO, experienced distinct photophysical modulation effect by SDS assemblies. The ensemble based on PO@SDS assemblies displayed effective fluorescence variation to antibiotic aminoglycosides (AGs). To improve cross-reactivity and discrimination capability of ensembles, a second probe, coumarin, was introduced into PO@SDS assemblies. The resultant ternary sensor, CM-PO@SDS, exhibited good qualitative and quantitative detection capabilities, and achieved differentiation of eight AGs and mixed AG samples both in aqueous solution and actual biological fluid, like human serum. Sensing mechanism studies revealed that hydrogen bonding, electrostatic and hydrophobic interactions are involved in the sensing process. This surfactant-based fluorescent ensemble provides a simple and feasible method for assessing AGs levels. Meanwhile, this work may provide some insights to design reasonable probes for constructing effective single-system based discriminative fluorescent amphiphilic sensors.

Using Hybrid PDI-Fe3O4 Nanoparticles for Capturing Aliphatic Alcohols: Halogen Bonding vs. Lone Pair-π Interactions.

In this study, Fe3O4 nanoparticles (FeNPs) decorated with halogenated perylene diimides (PDIs) have been used for capturing VOCs (volatile organic compounds) through noncovalent binding. Concretely, we have used tetrachlorinated/brominated PDIs as well as a nonhalogenated PDI as a reference system. On the other hand, methanol, ethanol, propanol, and butanol were used as VOCs. Experimental studies along with theoretical calculations (the BP86-D3/def2-TZVPP level of theory) pointed to two possible and likely competitive binding modes (lone pair-π through the π-acidic surface of the PDI and a halogen bond via the σ-holes at the Cl/Br atoms). More in detail, thermal desorption (TD) experiments showed an increase in the VOC retention capacity upon increasing the length of the alkyl chain, suggesting a preference for the interaction with the PDI aromatic surface. In addition, the tetrachlorinated derivative showed larger VOC retention times compared to the tetrabrominated analog. These results were complemented by several state-of-the-art computational tools, such as the electrostatic surface potential analysis, the Quantum Theory of Atoms in Molecules (QTAIM), as well as the noncovalent interaction plot (NCIplot) visual index, which were helpful to rationalize the role of each interaction in the VOC···PDI recognition phenomena.

Hypericin-mediated photodynamic therapy inhibits metastasis and EMT of colorectal cancer cells by regulating RhoA-ROCK1 signaling pathway.

Colorectal cancer (CRC) is significantly contributed to global cancer mortality rates. Treating CRC is particularly challenging due to metastasis and drug resistance. There is a pressing need for new treatment strategies against metastatic CRC. Photodynamic therapy (PDT) offers a well-established, minimally invasive treatment option for cancer with limited side effects. Hypericin (HYP), a potent photosensitizer for PDT, has been documented to induce cytotoxicity and apoptosis in various types of cancers. However, there are few reports on the inhibitory effects of HYP-mediated PDT on the metastatic ability of CRC cells. Here, we evaluate the inhibitory effects of HYP-mediated PDT against metastatic CRC cells and define its underlying mechanisms. Wound-healing and Transwell assays show that HYP-mediated PDT suppresses migration and invasion of CRC cells. F-actin visualization assays indicate HYP-mediated PDT decreases F-actin formation in CRC cells. TEM assays reveal HYP-mediated PDT disrupts pseudopodia formation of CRC cells. Mechanistically, immunofluorescence and western blotting results show that HYP-mediated PDT upregulates E-cadherin and downregulates N-cadherin and Vimentin. HYP-mediated PDT also suppresses key EMT regulators, including Snail, MMP9, ZEB1 and α-SMA. Additionally, the expressions of RhoA and ROCK1 are downregulated by HYP-mediated PDT. Together, these findings suggest that HYP-mediated PDT inhibits the migration and invasion of HCT116 and SW620 cells by modulating EMT and RhoA-ROCK1 signaling pathway. Thus, HYP-mediated PDT presents a potential therapeutic option for CRC.

Single-Photon Deep-Red Light-Triggered Direct Release of an Anticancer Drug: An Investigative Tumor Regression Study on a Breast Cancer Spheroidal Tumor Model.

Breast adenocarcinoma ranks high among the foremost lethal cancers affecting women globally, with its triple-negative subtype posing the greatest challenge due to its aggressiveness and resistance to treatment. To enhance survivorship and patients' quality of life, exploring advanced therapeutic approaches beyond conventional chemotherapies is imperative. To address this, innovative nanoscale drug delivery systems have been developed, offering precise, localized, and stimuli-triggered release of anticancer agents. Here, we present perylenemonoimide nanoparticle-based vehicles engineered for deep-red light activation, enabling direct chlorambucil release. Synthesized via the reprecipitation technique, these nanoparticles were thoroughly characterized. Light-induced drug release was monitored via spectroscopic and reverse-phase HPLC. The efficacy of the said drug delivery system was evaluated in both two-dimensional and three-dimensional spheroidal cancer models, demonstrating significant tumor regression attributed to apoptotic cell death induced by efficient drug release within cells and spheroids. This approach holds promise for advancing targeted breast cancer therapy, enhancing treatment efficacy and minimizing adverse effects.

A perylene diimide probe for NIR-II fluorescence imaging guided photothermal and type I/type II photodynamic synergistic therapy.

Phototherapy has garnered significant attention in the past decade. Photothermal and photodynamic synergistic therapy combined with NIR fluorescence imaging has been one of the most attractive treatment options because of the deep tissue penetration, high selectivity and excellent therapeutic effect. Benefiting from the superb photometrics and ease of modification, perylene diimide (PDI) and its derivatives have been employed as sensing probes and therapeutic agents in the biological and biomedical research fields, and exhibiting excellent potential. Herein, we reported the development of a novel organic small-molecule phototherapeutic agent, PDI-TN. The absorption of PDI-TN extends into the NIR region, which provides feasibility for NIR phototherapy. PDI-TN overcomes the traditional Aggregation-Caused Quenching (ACQ) effect and exhibits typical characteristics of Aggregation-Induced Emission (AIE). Subsequently, PDI-TN NPs were obtained by using an amphiphilic triblock copolymer F127 to encapsulate PDI-TN. Interestingly, the PDI-TN NPs not only exhibit satisfactory photothermal effects, but also can generate O2•- and 1O2 through type I and type II pathways, respectively. Additionally, the PDI-TN NPs emit strong fluorescence in the NIR-II region, and show outstanding therapeutic potential for in vivo NIR-II fluorescence imaging. To our knowledge, PDI-TN is the first PDI derivative used for NIR-II fluorescence imaging-guided photodynamic and photothermal synergistic therapy, which suggests excellent potential for future biological/biomedical applications.

Photodynamic antibacterial research on hypericin-loaded PEGylated mesoporous silica delivery system.

In this study, a novel drug delivery system (MSN-PEG-Hypericin) was successfully fabricated using tetraethyl orthosilicate and 3-aminopropyltriethoxysilane as raw materials, and the PEGylation of the prepared aminated mesoporous silica and grafting of hypericin onto the carrier were further conducted to obtain MSN-PEG-Hypericin. The successful preparation of MSN-PEG-Hypericin was characterized by several physical-chemical techniques. Furthermore, the MSN-PEG-Hypericin system increased the ability of hypericin to generate reactive oxygen species (ROS) in vitro. The cytotoxicity assay and hemolysis analysis showed that MSN-PEG-Hypericin had good biocompatibility. For antibacterial studies, the irradiation time and incubation time of photodynamic therapy (PDT) for S. aureus and E. coli were respectively 8 min and 8 h, and the concentrations of hypericin were 2.5 and 5 µg/mL. The result of triphenyl tetrazolium chloride assay indicated that MSN-PEG-Hypericin had stronger photodynamic antibacterial activity than free hypericin, and S. aureus was more sensitive to PDT than E. coli, which was related to their cell structural differences. The antibacterial mechanism study indicated that the generated ROS could destroy the bacterial structures and cause bacterial death due to the leakage of the contents. The MSN-PEG-Hypericin system prepared in this study had potential application prospects in the antibacterial field.

Chemo-photodynamic antitumour therapy based on Er-doped upconversion nanoparticles coated with hypocrellin B and MnO2.

An antitumour chemo-photodynamic therapy nanoplatform was constructed based on phospholipid-coated NaYF4: Yb/Er upconversion nanoparticles (UCNPs). In this work, the amphiphilic block copolymer DSPE-PEG2000 was combined with the surface ligand oleic acid of the UCNPs through hydrophobic interaction to form liposomes with a dense hydrophobic layer in which the photosensitizer hypocrellin B (HB) was assembled. The coated HB formed J-aggregates, which caused a large redshift in the absorption spectrum and improved the quantum efficiency of energy transfer. Furthermore, MnO2 nanosheets grew in-situ on the liposomes through OMn coordination. Therefore, a multifunctional tumour microenvironment (TME)-responsive theranostic nanoplatform integrating photodynamic therapy (PDT) and chemodynamic therapy (CDT) was successfully developed. The results showed that this NIR-mediated chemo-photodynamic therapy nanoplatform was highly efficient for oncotherapy.

Development of a sensitive electrochemical method to determine amitraz based on perylene tetracarboxylic acid/mesoporous carbon/Nafion@SPCEs.

A cutting-edge electrochemical method is presented for precise quantification of amitraz (AMZ), a commonly used acaricide in veterinary medicine and agriculture. Leveraging a lab-made screen-printed carbon electrode modified with a synergistic blend of perylene tetracarboxylic acid (PTCA), mesoporous carbon (MC), and Nafion, the sensor's sensitivity was significantly improved. Fine-tuning of PTCA, MC, and Nafion ratios, alongside optimization of the pH of the supporting electrolyte and accumulation time, resulted in remarkable sensitivity enhancements. The sensor exhibited a linear response within the concentration range 0.01 to 0.70 µg mL-1, boasting an exceptionally low limit of detection of 0.002 µg mL-1 and a limit of quantification of 0.10 µg mL-1, surpassing maximum residue levels permitted in honey, tomato, and longan samples. Validation with real samples demonstrated high recoveries ranging from 80.8 to 104.8%, with a relative standard deviation below 10%, affirming the method's robustness and precision. The modified PTCA/MC/Nafion@SPCE-based electrochemical sensor not only offers superior sensitivity but also simplicity and cost-effectiveness, making it a pivotal tool for accurate AMZ detection in food samples. Furthermore, beyond the scope of this study, the sensor presents promising prospects for wider application across various electrochemical analytical fields, thereby significantly contributing to food safety and advancing agricultural practices.

Brain-Targeted Black Phosphorus-Based Nanotherapeutic Platform for Enhanced Hypericin Delivery in Depression.

Depression is a significant global health concern that remains inadequately treated due to the limited effectiveness of conventional drug therapies. One potential therapeutic agent, hypericin (HYP), is identified as an effective natural antidepressant. However, its poor water solubility, low bioavailability, and limited ability to penetrate the brain parenchyma have hindered its clinical application. To address these shortcomings and enhance the therapeutic efficacy of HYP, it is loaded onto black phosphorus nanosheets (BP) modified with the neural cell-targeting peptide RVG29 to synthesize a nanoplatform named BP-RVG29@HYP (BRH). This platform served as a nanocarrier for HYP and integrated the advantages of BP with advanced delivery methods and precise targeting strategies. Under the influence of 808 nm near-infrared irradiation (NIR), BRH effectively traversed an in vitro BBB model. In vivo experiments validated these findings, demonstrating that treatment with BRH significantly alleviated depressive-like behaviors and oxidative stress in mice. Importantly, BRH exhibited an excellent safety profile, causing minimal adverse effects, which highlighted its potential as a promising therapeutic agent. In brief, this novel nanocarrier holds great promise in the development of antidepressant drugs and can create new avenues for the treatment of depression.

Perylene-Mediated Cytoskeletal Dysfunction Remodels Cancer-Associated Fibroblasts to Augment Antitumor Immunotherapy.

Targeted reprogramming of cancer-associated fibroblasts (CAFs) is one of the most essential cancer therapies. However, how to reprogram active CAFs toward deactivated state still remains immense challenge. To tackle this challenge, herein, one perylene N, N'-bis(2-((dimethylammonium)ethylene)-2-(methoxylethyl))-1, 6, 7, 12-tetrachloroperylene-3, 4, 9, 10-tetracarboxylic diimide (PDIC-OC) is prepared, which can trigger endogenous reactive oxygen species (ROS) burst to result in cytoskeletal dysfunction and cell apoptosis so that suppress transforming growth factor ß (TGF-ß) production. As a result, PDIC-OC can reprogram the activated CAFs and relieve immunosuppressive tumor microenvironment by efficient polarization of M2-typed macrophages into M1-typed ones, downregulation of alpha-smooth muscle actin (α-SMA), alleviation of hypoxic state to promote infiltration of cytotoxic T lymphocytes, and ultimately realizes outstanding antitumor performance on B16F10 tumor-xenografted and lung-metastatic mouse model even at low concentration of 1 mg kg-1 body weight. This work thus presents a novel strategy that cytoskeleton dysfunction and cell apoptosis cooperatively suppress the secretion of TGF-ß to reprogram CAFs and meanwhile clarifies intrinsic mechanism for perylene-triggered chemo-immunotherapy against hypoxic tumors.

Complexed Photosensitizer of Hypericin with G-Quadruplex: Structure-Dependent Behavior.

Despite the increased interest of visible-light-absorbing compound Hypericin (Hyp) in photodiagnosis, photocatalysis, and photodynamic therapy (PDT) applications, a major obstacle still exists; i.e., the photoactivity is diminished due to the facile aggregation of Hyp in aqueous environment that induces excited-state quenching. Herein, we explore the excited-state property of Hyp bound to the DNA G-quadruplex by combining multiple steady-state and time-resolved spectroscopy. We find that the aggregation-induced quenching effect can be successfully prevented by appropriate G-quadruplex binders that disperse Hyp into monomer. The binding of Hyp/G-quadruplex is selective, however, exhibiting a preferential binding toward parallel G-quadruplexes (c-kit2, C14B1, STAT3, S50, and PS2.M), over antiparallel or hybrid G-quadruplex (Tel22, TBA). The excited-state property of Hyp is highly related to the binding behavior, showing a consistent trend that the better the Hyp/G-quadruplex binding, the longer the triplet 3Hyp* lifetime and the higher the efficiency to produce 1O2. For Hyp/c-kit2, the major binding mode is 5'-end stacking, which offers protection from collisional quenching reactions and ensures a stable photocycle of 3Hyp*-O2 energy transfer forming 1O2, leading to the highest 1O2 quantum yield (0.67) with superior photostability. These findings open possibilities of developing Hyp/G-quadruplex complex as a biocompatible photosensitizer for PDT applications, etc.

A Self-Assembly-Induced Exciton Delocalization Strategy for Converting a Perylene Diimide Derivative from a Type-II to Type-I Photosensitizer.

Type-I photosensitizers have shown advantages in addressing the shortcomings of traditional oxygen-dependent type-II photosensitizers for the photodynamic therapy (PDT) of hypoxic tumors. However, developing type-I photosensitizers is yet a huge challenge because the type-II energy transfer process is much faster than the type-I electron transfer process. Herein, from the fundamental point of view, an effective approach is proposed to improve the electron transfer efficiency of the photosensitizer by lowering the internal reorganization energy and exciton binding energy via self-assembly-induced exciton delocalization. An example proof is presented by the design of a perylene diimide (PDI)-based photosensitizer (PDIMp) that can generate singlet oxygen (1O2) via a type-II energy transfer process in the monomeric state, but induce the generation of superoxide anion (O2˙-) via a type-I electron transfer process in the aggregated state. Significantly, with the addition ofcucurbit[6]uril (CB[6]), the self-assembled PDIMp can convert back to the monomeric state via host-guest complexation and consequently recover the generation of 1O2. The biological evaluations reveal that supramolecular nanoparticles (PDIMp-NPs) derived from PDIMp show superior phototherapeutic performance via synergistic type-I PDT and mild photothermal therapy (PTT) against cancer under either normoxia or hypoxia conditions.

Toward Type I/II ROS Generation Photoimmunotherapy by Molecular Engineering of Semiconducting Perylene Diimide.

As prospective phototheranostic agents for cancer imaging and therapy, semiconducting organic molecule-based nanomedicines are developed. However, near-infrared (NIR) emission, and tunable type I (O2 • -) and type II (1O2) photoinduced reactive oxygen species (ROS) generation to boost cancer photoimmunotherapy remains a big challenge. Herein, a series of D-π-A structures, NIR absorbing perylene diimides (PDIs) with heavy atom bromide modification at the bay position of PDIs are prepared for investigating the optimal photoinduced type I/II ROS generation. The heavy atom effect has demonstrated a reduction of molecular ∆EST and promotion of the intersystem crossing processes of PDIs, enhancing the photodynamic therapy (PDT) efficacy. The modification of three bromides and one pyrrolidine at the bay position of PDI (TBDT) has demonstrated the best type I/II PDT performance by batch experiments and theoretical calculations. TBDT based nanoplatforms (TBDT NPs) enable type I/II PDT in the hypoxic tumor microenvironment as a strong immunogenic cell death (ICD) inducer. Moreover, TBDT NPs showing NIR emission allow in vivo bioimaging guided phototherapy of tumor. This work uses novel PDIs with adjustable type I/II ROS production to promote antitumor immune response and accomplish effective tumor eradication, consequently offering molecular guidelines for building high-efficiency ICD inducers.

Hypericin supramolecular assembles: A way to increase the skin availability and photodynamic efficiency in tumor cells.

Cyclodextrins (CDs) are molecules approved by the FDA and show promise in increasing the solubility of hydrophobic molecules and making them more available to the skin. These CDs have been used to form complexes with some photosensitizers for Photodynamic Therapy (PDT), such as Hypericin (HY). HY is a lipophilic photosensitizer known for its exceptional fluorescence and singlet oxygen quantum yield generation of over 20 % under 590 nm irradiation. In this study, we found a six-fold increase in the release of HY in vitro after complexation with ß-CD. The ß-CDHY assembly also demonstrated better skin retention, which is crucial for the topical application of this photosensitizer. Furthermore, the ß-CD complexation led to a significant increase in the phototoxicity of HY at three different light doses (3, 6, and 10 J cm-2) due to its improved water solubility and higher in vitro accumulation (approximately two times compared with free HY) in HeLa and Vero cell lines.