Promising Photodynamic Therapy Research Articles

A Nanoencapsulated Ir(III)-Phthalocyanine Conjugate as a Promising Photodynamic Therapy Anticancer Agent.

Despite the potential of photodynamic therapy (PDT) in cancer treatment, the development of efficient and photostable photosensitizing molecules that operate at long wavelengths of light has become a major hurdle. Here, we report for the first time an Ir(III)-phthalocyanine conjugate (Ir-ZnPc) as a novel photosensitizer for high-efficiency synergistic PDT treatment that takes advantage of the long-wavelength excitation and near infrared (NIR) emission of the phthalocyanine scaffold and the known photostability and high phototoxicity of cyclometalated Ir(III) complexes. In order to increase water solubility and cell membrane permeability, the conjugate and parent zinc phthalocyanine (ZnPc) were encapsulated in amphoteric redox-responsive polyurethane-polyurea hybrid nanocapsules (Ir-ZnPc-NCs and ZnPc-NCs, respectively). Photobiological evaluations revealed that the encapsulated Ir-ZnPc conjugate achieved high photocytotoxicity in both normoxic and hypoxic conditions under 630 nm light irradiation, which can be attributed to dual Type I and Type II reactive oxygen species (ROS) photogeneration. Interestingly, PDT treatments with Ir-ZnPc-NCs and ZnPc-NCs significantly inhibited the growth of three-dimensional (3D) multicellular tumor spheroids. Overall, the nanoencapsulation of Zn phthalocyanines conjugated to cyclometalated Ir(III) complexes provides a new strategy for obtaining photostable and biocompatible red-light-activated nano-PDT agents with efficient performance under challenging hypoxic environments, thus offering new therapeutic opportunities for cancer treatment.

Third-Generation Anticancer Photodynamic Therapy Systems Based on Star-like Anionic Polyacrylamide Polymer, Gold Nanoparticles, and Temoporfin Photosensitizer.

Photodynamic therapy (PDT) is a non-invasive anticancer treatment that uses special photosensitizer molecules (PS) to generate singlet oxygen and other reactive oxygen species (ROS) in a tissue under excitation with red or infrared light. Though the method has been known for decades, it has become more popular recently with the development of new efficient organic dyes and LED light sources. Here we introduce a ternary nanocomposite: water-soluble star-like polymer/gold nanoparticles (AuNP)/temoporfin PS, which can be considered as a third-generation PDT system. AuNPs were synthesized in situ inside the polymer molecules, and the latter were then loaded with PS molecules in an aqueous solution. The applied method of synthesis allows precise control of the size and architecture of polymer nanoparticles as well as the concentration of the components. Dynamic light scattering confirmed the formation of isolated particles (120 nm diameter) with AuNPs and PS molecules incorporated inside the polymer shell. Absorption and photoluminescence spectroscopies revealed optimal concentrations of the components that can simultaneously reduce the side effects of dark toxicity and enhance singlet oxygen generation to increase cancer cell mortality. Here, we report on the optical properties of the system and detailed mechanisms of the observed enhancement of the phototherapeutic effect. Combinations of organic dyes with gold nanoparticles allow significant enhancement of the effect of ROS generation due to surface plasmonic resonance in the latter, while the application of a biocompatible star-like polymer vehicle with a dextran core and anionic polyacrylamide arms allows better local integration of the components and targeted delivery of the PS molecules to cancer cells. In this study, we demonstrate, as proof of concept, a successful application of the developed PDT system for in vitro treatment of triple-negative breast cancer cells under irradiation with a low-power LED lamp (660 nm). We consider the developed nanocomposite to be a promising PDT system for application to other types of cancer.

The Potential of Narrow-Band Imaging as a Novel Light Source for Photodynamic Therapy for Superficial Cancers via Endoscopes.

Photodynamic therapy (PDT) has advanced through the utilization of photosensitizers and specific-wavelength light (≥ 600 nm). However, the widespread adoption of PDT is still impeded by high equipment costs and stringent laser safety requirements. Porphyrins, crucial in PDT, have another absorbance peak of blue light (λ = 380 - 500 nm). This peak corresponds to the wavelength of narrow-band imaging (NBI) (λ = 390 - 445 nm), an image-enhancement technology integrated into endoscopes by Olympus Medical Systems. The study aimed to investigate the potential of widely adopted NBI as a PDT light source for superficial cancers via endoscopes. Esophageal and biliary cancers were selected for investigation. Human esophageal cancer cell lines (KYSE30, KYSE70, KYSE170) and cholangiocarcinoma cell lines (HuCCT-1, KKU-213) were subjected to verteporfin-mediated PDT under NBI light (λ = 390 - 445 nm). Assessments included spectrometry, crystal violet staining, and fluorescein imaging of singlet oxygen generation and apoptosis. Verteporfin exhibited a peak (λ = 436 nm) consistent with the NBI spectrum, suggesting compatibility with NBI light. NBI light significantly inhibited the growth of esophageal and biliary cancer cells. The half-maximum effective concentration (EC50) values (5 J/cm2) for KYSE30, KYSE70, KYSE170, HuCCT-1, and KKU-213 were calculated as 2.78 ± 0.37µM, 1.76 ± 1.20 µM, 0.77 ± 0.16 µM, 0.65 ± 0.18 µM, and 0.32 ± 0.04 µM, respectively. Verteporfin accumulation in mitochondria, coupled with singlet oxygen generation and observed apoptotic changes, suggests effective PDT under NBI light. NBI is a promising PDT light source for superficial cancers via endoscopes.

Rational design of type-I photosensitizer molecules for mitochondrion-targeted photodynamic therapy.

Photodynamic therapy (PDT) has emerged as a promising approach for tumor treatment. However, traditional type II PDT faces limitations due to its oxygen-dependent nature. Type-I photosensitizers (PSs) exhibit superiority over conventional type-II PSs owing to their diminished oxygen dependence. Nevertheless, designing effective type-I PSs remains a significant challenge. In this work, we provide a novel strategy to tune the PDT mechanism of an excited photosensitizer through aryl substituent engineering. Using S-rhodamine as the base structure, three PSs were synthesized by incorporating phenyl, furyl, or thienyl groups at the meso position. Interestingly, furyl- or thienyl-substituted S-rhodamine are type-I-dominated PSs that produce O2˙-, while phenyl S-rhodamine results in O2˙- and 1O2 through type-I and type-II mechanisms, respectively. Experimental analyses and theoretical calculations showed that the introduction of a five-membered heterocycle at the meso position promoted intersystem crossing (ISC) and electron transfer, facilitating the production of O2˙-. Furthermore, furyl- or thienyl-substituted S-rhodamine exhibited high phototoxicity at ultralow concentrations. Thienyl-substituted S-rhodamine showed promising PDT efficacy against hypoxic solid tumors. This innovative strategy provides an alternative approach to developing new type-I PSs without the necessity for creating entirely new skeletons.

Design, synthesis, and evaluation of 5,15-diaryltetranaphtho [2,3]porphyrins as photosensitizers in real-time photodynamic therapy and photodiagnosis

In the pursuit of new potent photosensitizers (PSs) for photodynamic therapy (PDT) with better efficacy, a series of 5,15-diaryltetranaphtho [2,3]porphyrins (Ar2TNPs) with two or four carboxyalkoxy groups were designed, synthesized, and evaluated. These new compounds exhibited strong, broad and red-shifted UV–vis absorptions at 729 nm and other strong absorptions at 446, 475, 650, 659, 714 nm for tumors and other diseases of varying sizes and depths. They possess high molar extinction coefficients (0.95 × 105–1.48 × 105 M−1 cm−1), good singlet oxygen quantum yields and photodynamic antitumor effects towards Eca-109 cells in vitro. It is suggested that the extension of porphyrin with naphthalene into Ar2TNP results into remarkable improvement of photophysical characteristics, while the introduction of carboxyalkoxy groups on meso-phenyl can significantly improve the solubility and photodynamic effects in vitro and in vivo. Notably, compound II3 can localize primarily in lysosomes of Eca-109 cells and induce substantial cell apoptosis after PDT. It can also selectively accumulate in tumor tissues and be traced real-timely through in vivo fluorescence imaging with distinctive inhibition of tumor growth. Therefore, compound II3 deserves to be considered as a promising PDT drug candidate for individualized tumor real-time tracing and treatment.

Ru(II)-Cyanine Complexes as Promising Photodynamic Photosensitizers for the Treatment of Hypoxic Tumours with Highly Penetrating 770 nm Near-Infrared Light.

Light-activated treatments, such as photodynamic therapy (PDT), provide temporal and spatial control over a specific cytotoxic response by exploiting toxicity differences between irradiated and dark conditions. In this work, a novel strategy for developing near infrared (NIR)-activatable Ru(II) polypyridyl-based photosensitizers (PSs) was successfully developed through the incorporation of symmetric heptamethine cyanine dyes in the metal complex via a phenanthrimidazole ligand. Owing to their strong absorption in the NIR region, the PSs could be efficiently photoactivated with highly penetrating NIR light (770 nm), leading to high photocytotoxicities towards several cancer cell lines under both normoxic and hypoxic conditions. Notably, our lead PS (Ru-Cyn-1), which accumulated in the mitochondria, exhibited a good photocytotoxic activity under challenging low-oxygen concentration (2% O2) upon NIR light irradiation conditions (770 nm), owing to a combination of types I and II PDT mechanism. The fact that the PS Protoporphyrin IX (PpIX), the metabolite of the clinically approved 5-ALA PS, was found inactive under the same challenging conditions positions Ru-Cyn-1 complex as a promising PDT agent for the treatment of deep-seated hypoxic tumours.

Photophysical Insights of Halogenated Dipyrrolonaphthyridine-Diones as Potential Photodynamic Therapy Agents†.

We report the synthesis and photophysical characterization of novel halogenated dipyrrolonaphthyridine-diones (X2 -DPNDs, X=Cl, Br, and I), as candidates for photodynamic therapy (PDT) application. Apart from the heavy atom-induced spin-orbit coupling (SOC) dynamics in the investigated X2 -DPNDs, it was found that the position of the halogen atom (relative to the nitrogen of the pyrrole ring) also influenced the triplet excited state behavior. Interestingly, the faster/efficiency sensitization of 3 O2 to 1 O2 using X2 -DPND correlates with the rate of triplet population, kISC >1.6 × 108 s-1 for I2 -DPND vs kISC >2.9 × 109 s-1 for Cl2 -DPND and Br2 -DPND (where τISC =343 ± 3 ps for I2 -DPND and τISC =5-6 ns for Cl2 -DPND and Br2 -DPND are the lowest time constants/values for ISC). Furthermore, the heavy atom-induced SOC in Cl2 -DPND and Br2 -DPND did not lead to a reduction of the corresponding fluorescence (ca 75% vs 67% for the parent DPND). The attractive photophysical characteristics of Cl2 /Br2 -DPND put them on the landscape as not only promising PDT agents but also as fluorescence probes. The present study is a stepping stone in the development of novel organic photosystems for synergistic photomedicinal applications.

PEGylated poly(lactic-co-glycolic acid) nanoparticles doped with molybdenum-iodide nanoclusters as a promising photodynamic therapy agent against ovarian cancer

A photosensitizing nanosystem based on PEGylated PLGA nanoparticles doped with luminescent molybdenum-iodide nanoclusters displays advantageous features for photodynamic therapy of ovarian cancer.

BSA-coated β-FeOOH nanoparticles efficiently deliver the photosensitizer chlorin e6 for synergistic anticancer PDT/CDT

Photodynamic therapy (PDT) has many exceptional advantages in cancer treatment, such as minor trauma, low toxicity side effects, and strong adaptability, effectively overcoming some obstacles of traditional therapy and providing more revolutionary opportunities for curing cancer. Chlorin e6 (Ce6) exhibits excellent singlet oxygen generation and conversion efficiency under near-infrared laser irradiation and is a promising PDT photosensitizer. However, its hydrophobicity, short half-life and lack of tumor specificity limit its in vivo anticancer application. Therefore, this work has designed and prepared a multifunctional nanoplatform, Ce6/FeOOH@BSA, to efficiently deliver Ce6. Nanoparticles exhibit excellent dispersion and stability in deionized water, PBS and DMEM, and the blood half-life is 3.98 ± 0.31 h. The nanoplatform demonstrates effective tumor targeting and accumulation, overcoming the obstacles of the biological application of Ce6. Iron ions can exert a chemodynamic therapy (CDT) effect by reacting with overexpressed H2O2 in the tumor to generate toxic hydroxyl radicals (·OH). Moreover, FeOOH nanoparticles effectively promote glutathione (GSH) consumption in tumor cells, which is conducive to accumulating reactive oxygen species (ROS). In brief, Ce6/FeOOH@BSA nanoparticles realize the targeted delivery of Ce6 and mediate synergistic PDT/CDT against tumors, broadening the biomedical application of nanomaterials.

Topical methylene blue nanoformulation for the photodynamic therapy of acne vulgaris.

Acne vulgaris is a common skin disease caused by multifactorial reasons involving excessive sebum secretion and inflammation by Cutibacterium acnes (C. acnes). Various conventional therapies are available for the treatment of acne vulgaris; however, topical photodynamic therapy (PDT) has attracted much attention because of its great potential for sebum-reducing, anti-inflammatory, and antimicrobial activities. Although 5-aminolevulinic acid (ALA) has been broadly used as a photosensitizer for topical PDT, it has several limitations such as long incubation time, pain, and post-inflammatory hyperpigmentation. Here, we report a biocompatible nanoformulation consisting of methylene blue and salicylic acid (MBSD), as a potent PDT and acne therapeutics, enclosed within oleic acid. Photoactivated MBSD showed antimicrobial activity against C. acnes along with long-term stability. When 24 patients with acne were treated with MBSD and light irradiation 5 times at 1-week intervals, MBSD-based PDT exhibited a remarkable reduction in acne lesions and sebum production. In addition, the therapeutic procedure was painless and safe, without any adverse events. Therefore, MBSD is a promising topical PDT agent for biocompatible, safe, and effective acne treatment.

Aptamer-modified carbon dots for enhancement of photodynamic therapy of cancer cells

Carbon dots (CDs) have emerged as promising materials for photodynamic therapy (PDT) because of their intriguing photochemical properties, high stability, and low toxicity. However, achieving accurate delivery of CDs based photosensitizers into tumor sites remains a grand challenge. Herein, AS1411 aptamer, a short oligonucleotide sequence with high binding specificity to tumor cells, was chemically decorated to the surface of Asp-CDs to obtain Asp-CDs@AS1411. The aptamer modified Asp-CDs@AS1411 not only retains the excellent properties of Asp-CDs such as high singlet oxygen quantum yield (up to 50%), bright photoluminescence, and good stability, but also features specific recognition and markedly enhanced phototoxicity (4 times) to tumor cells. These combined attributes make Asp-CDs@AS1411 a promising PDT agent for efficient tumor treatment. More importantly, the reported strategy paves a new avenue for developing high performance PDT materials from surface functionalized CDs featuring high photosensitivity and targeting ability.

Tumor Selective Metabolic Reprogramming as a Prospective PD-L1 Depression Strategy to Reactivate Immunotherapy.

Currently, the role of the lysosome, endoplasmic reticulum, or dictyosome in the transcription and translation of programmed cell death ligand 1 (PD-L1) is well revealed, but the role and function of mitochondria in the PD-L1expression in tumors is still not fully researched, making it hard to offer a novel PD-L1regulation strategy. In this research, it is newly revealed that mitochondria oxidative phosphorylation (OXPHOS) depression can be used as an effective PD-L1down-regulation method. To offer an ideal and high-effective tumor mitochondria-targeted OXPHOS depression nanosystem, IR-LND is prepared by conjugating mitochondria-targeted heptamethine cyanine dye IR-68with mitochondrial complexes I and II depression agent lonidamine (LND), which then further self-assembled with albumin (Alb) to form IR-LND@Alb nanoparticles. By doing this, PD-L1expression in tumors is selectively and effectively depressed by IR-LND@Alb nanoparticles. As expected, the anti-tumor efficacy of such a PD-L1depression strategy is superior to conventional anti-PD-L1monoclonal antibodies. Interestingly, IR-LND can also be served as a novel ideal promising photodynamic therapy (PDT) drug with self-oxygen and self-PD-L1regulation capacity. All in all, this tumor-selective metabolic reprogramming platform to reactivate immunotherapy and sensitize for PDT effect, would open a new window for mitochondrial immunotherapy for cancer patients.

Diethynylarene-linked bis(triarylborane)cations as theranostic agents for tumor cell and virus-targeted photodynamic therapy

We recently reported diethynylarene-linked bis(triarylborane) tetracations which show remarkable fluorimetric and Raman-SERS sensing of DNA/RNA. In the current study, we show that they exhibit promising photodynamic therapy (PDT)-based biological activity on human cell lines and adenovirus type 5 (HAdV5), acting as theranostic agents. All compounds efficiently enter living cells showing negligible antiproliferative activity. Bis-thiophene- and anthracene- analogues bind non-covalently to HAdV5 virus with high affinity, the anthracene-analogue itself causing a moderate antiviral effect, i.e., decreased ability of the virus to infect human cells. Irradiation of bis-thiophene- and anthracene- analogues with visible light (400-700nm) caused a very rapid (within 1min) and strong increase in cytotoxicity, as well as an order of magnitude increase in antiviral activity, attributed to the formation of reactive oxygen species (ROS). Photochemical studies of the compounds revealed that, upon irradiation, they produce singlet oxygen, which correlates with the observed light-induced bioactivity.

Effects of polyallylamine-coated nanoparticles on the optical and photochemical properties of rose bengal.

Inasmuch as optical and photochemical properties of a photosensitizer can be modified upon association with the nanoparticle (NP), we wondered whether the effectiveness of phototherapeutic rose bengal (RB) was affected upon tethering to the sodium lanthanide fluoride NP with an outer polyallylamine (PAH) coat. RB molecules were electrostatically bound to the NaYF 4 :Gd 3+ :Nd 3+ NPs with inner silica and outer PAH coats. The products were analyzed for their size, shape and zeta potential using transmission electron microscopy and dynamic light scattering instrument. Ultraviolet-visible absorption spectrometry and fluorescence spectrometry were used to examine the spectral properties. Photodynamic effect in terms of singlet oxygen generation was quantitatively determined using the indicator 1,3-diphenylisobenzofuran (DPBF). Photocytotoxicity mediated by NP-bound RB was tested using A549 cells (Student's t test was used for statistical evaluation). NP-bound RB had the major absorbance peak at 561 nm, in comparison with 549 nm for free RB, accompanied with a significant decrease in absorptivity. The molar extinction coefficient becomes 36 000 M -1 cm -1 , only ~35% of that for free RB. Fluorescence spectral analyses showed a paradoxical decrease in the emission with higher NP concentrations even at very low dilutions. Most importantly, the association of RB with these NPs drastically increased its singlet oxygen production upon irradiation. The interaction of RB with PAH coat could partly account for this enhancement, given our finding that PAH in solution also caused a drastic rise in DPBF reactivity by free RB. These NPs exhibited strong photocytotoxic effects, and their promise in photodynamic therapy was addressed. Our findings provide evidence that the PAH coat plays a key role in enhanced biological activities of RB delivered via NPs, including the increase in singlet oxygen production and photocytotoxic effects.

Investigation on the in vitro anti-Trichophyton activity of photosensitizers.

Onychomycosis is the most common disease caused by fungal nail infections, and often caused by dermatophytes. This infection is very resistant to antifungal treatments, and promising Photodynamic Therapy (PDT) mediated treatments has been presented as a multitarget tracking. Optimization of PDT guide for uptake time, concentration of photosensitizers (PS) and the light dose to inactivate Trichophyton mentagrophytes. Curcumin derivatives, porphyrin Chlorin e6 (CHL-E6) and Chlorin-P6-6-N-butylamide-7-methyl-ester (CHL-butyl) were evaluated. PS photobleaching was observed on the hyphae photosensitized over the time, correlating the PS concentration and light dose of antifungal PDT. Porphyrin, Curcumin, Chl-e6 and Chl-butyl concentrations of 2.5µg/mL, 0.025µg/mL, 10µg/mL and 5µg/mL respectively, under illumination of 10.5J/cm2 were the best antifungal conditions found in the study. Curcumin, in low concentrations, and chlorin were the PSs with higher activity anti-T. mentagrophytes.

Luminescence-Tunable ZnS-AgInS2 Nanocrystals for Cancer Cell Imaging and Photodynamic Therapy.

A highly luminescent I-III-VI group of semiconductor nanocrystals (NCs) has attracted considerable attention for applications in biomedical engineering and design of novel optoelectronic devices. In this work, high quality ZnS-AgInS2 (ZAIS) solid solution NCs were synthesized by thermal decomposition of a organometallic diethyldithiocarbamate precursor complex of (AgIn)xZn2(1-x) (S2CN(C2H5)2)4 in the presence of specific stabilizing and structure directing agents. By changing the composition of the precursor complex (value of x), the structure and optical property could easily be adjustable, thus leading to the formation of nanowire, nanorod, and tetrapod-like NCs and highly luminescent green to yellow to red color tunable NCs. The ZAIS NCs were further transferred to aqueous medium by 3-mercaptopropionic acid (MPA) capping without losing any optical properties. The color-tunable, water-soluble, and biocompatible ZAIS NCs were utilized for the in vitro cellular imaging of human cervical cancer cells (HeLa cells) and showed intense localization in the cell cytoplasm after 6 h of incubation. In addition, the inherent photocatalytic property of ZAIS NCs under light illumination showed promising photodynamic therapy of cancer cells, and thus, ZAIS NCs could be a promising candidate for future biomedical applications.

Skin-safe nanophotosensitizers with highly-controlled synthesized polydopamine shell for synergetic chemo-photodynamic therapy

Although photodynamic therapy (PDT) has been extensively studied as an established modality of cancer treatment, it still suffers from a few clinical limitations, such as skin phototoxicity and tumor hypoxia. To circumvent these hurdles, hollow silica mesoporous nanoparticles (HMSNs) loaded with photosensitizers were employed as the nanoplatform to construct multifunctional nanoparticles (NPs). Specifically, an ultra-uniform polydopamine (PDA) shell was highly controlled grown around HMSNs by photogenerated outwards-diffused 1O2, followed by conjugation of folic acid-poly(ethylene glycol) and chelation of Fe2+ ions. Thanks to the optimal thickness of light-absorbing PDA shell, the multifunctional NPs exhibited not only negligible skin phototoxicity but also efficient 1O2 generation and photothermal (PT)-enhanced •OH generation upon respective photoirradiation. Anti-tumor therapy was then performed on both 4 T1 tumor cells and tumor-bearing mice by the combination of 638 nm PDT and 808 nm PT-enhanced chemodynamic therapy (CDT). As a result, high therapeutic efficacy was achieved compared to single-modality therapy, with a cell inhibitory rate of 86% and tumor growth inhibition of 70.4% respectively. More interestingly, tumor metastasis was effectively inhibited by the synergetic treatment. These results convincingly demonstrate that our multifunctional NPs are very promising skin-safe PDT agents combined with CDT for efficient tumor therapy.

Light-Triggered Adhesive Silk-Based Film for Effective Photodynamic Antibacterial Therapy and Rapid Hemostasis.

Successful control of massive hemorrhage in deep wounds with irregular shape and low elasticity still remains great challenges in the clinic. As the wound sites are usually at risk of bacterial infection, it is necessary to design an ideal hemostatic agent with rapid hemostasis and excellent antibacterial activity. In this study, we developed a light responsive hemostatic film for effective handling of liver bleeding with promising photodynamic therapy against S. aureus onnear infrared (NIR) irradiation. Based on silk fibroin, the film exhibited desirable biocompatibility and mechanical property as a hemostat tape. Significantly, the film tape achieved excellent tissue adhesion and hemostasis in vivo within 2 min of UV exposure, which would have a great potential as a multifunctional biomedical material in the field of tissue repair such as wound healing, bone repair, and nerve regeneration.

Mesoporous Silica-Coated Upconverting Nanorods for Singlet Oxygen Generation: Synthesis and Performance.

Photodynamic therapy (PDT) has been reported as a possible pathway for the treatment of tumors. The exploration for promising PDT systems thus attracts continuous research efforts. This work focused on an ordered core–shell structure encapsulated by mesoporous SiO2 with the upconverting emission property following a surfactant-assisted sol–gel technique. The mesoporous silica shell possessed a high surface area-to-volume ratio and uniform distribution in pore size, favoring photosensitizer (rose bengal) loading. Simultaneously, upconverting nanocrystals were synthesized and used as the core. After modification via hydrophobic silica, the hydrophobic upconverting nanocrystals became hydrophilic ones. Under near-infrared (NIR) light irradiation, the nanomaterials exhibited strong green upconverting luminescence so that rose bengal could be excited to produce singlet oxygen. The photodynamic therapy (PDT) feature was evaluated using a 1O2 fluorescent indicator. It was found that this core–shell structure generates 1O2 efficiently. The novelty of this core–shell structure was the combination of upconverting nanocrystals with a mesoporous SiO2 shell so that photosensitizer rose bengal could be effectively adsorbed in the SiO2 shell and then excited by the upconverting core.

Investigating Antibacterial Efficiency and Mechanism of Oligo-thiophenes under White Light and Specific Biocidal Activity against E. coli in Dark.

More strategies are required to develop better photosensitizers for photodynamic therapy (PDT). As oligo(phenylene-ethynylene) electrolytes (OPE), oligo(thiophene)s with primary amine as pendant groups (P-OT), and oligo(thiophene ethynylene) (OTE) exhibit excellent light-induced biocidal activity, we desire to converge the molecular design principles of these three kinds of antibacterial agents to combine their advantages to obtain high efficiency and economic biocides. Thus, four oligo(thiophene)s (OTs) were designed and synthesized in this study. The light-induced and dark antibacterial efficacy of the four OTs against Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) were both evaluated. Notably, all the OTs present high biocidal efficacy in the broad spectrum at low (micromolar) concentrations after white-light irradiation. In particular, the low cell cytotoxicity of OTs exhibits their good biocompatibility. These results illustrate that the OTs could work as promising PDT biocides. Interestingly, OT-3 shows a strong and specific dark killing activity against E. coli. The higher biocidal efficacy of T-OTs compared with that of Q-OTs confirms the tertiary amine is a better pendant group for π-conjugated antibacterial agents against E. coli. Mechanistic investigation proves ROS is the necessary element for antibiosis under white light. The interacting efficacy of the OT to the cell membrane, involving synergistic effects between hydrophilic-hydrophobic interactions and electrostatic attractions, is also critical in the killing process. The membrane intercalating activity plays a more essential role, as indicated by the antibacterial activity of OTs. The results provide a unique insight into the relationship between molecular structure and antibacterial activities of this class of antibacterial agents.