A Tumor-Targeting Near-Infrared Heptamethine Cyanine Photosensitizer with Twisted Molecular Structure for Enhanced Imaging-Guided Cancer Phototherapy.

In recent years, cancer phototherapy has been extensively studied as noninvasive cancer treatment. To present efficient recognition toward cancer cells, most photosensitizers (PSs) are required to couple with tumor-targeted ligands. Interestingly, the heptamethine cyanine IR780 displays an intrinsic tumor-targeted feature even without modification. However, the photothermal efficacy and photostability of IR780 are not sufficient enough for clinical use. Herein, we involve a twisted structure of tetraphenylethene (TPE) between two molecules of IR780 to improve the photothermal conversion efficiency (PCE). The obtained molecule T780T shows strong near-infrared (NIR) fluorescence and improved PCE (38.5%) in the dispersed state. Also, the photothermal stability and ROS generation capability of T780T at the NIR range (808 nm) are both promoted. In the aqueous phase, the T780T was formulated into uniform nanoaggregates (∼200 nm) with extremely low fluorescence and PTT response, which would reduce in vivo imaging background and side effect of PTT response in normal tissues. After intravenous injection into tumor-bearing mice, the T780T nanoaggregates display high tumor accumulation and thus remarkably inhibit the tumor growth. Moreover, the enhanced photostability of the T780T allows for twice irradiation after one injection and leads to more significant tumor inhibition. In summary, our study presents a tumor-targeted small-molecule PS for efficient cancer therapy and brings a new design of heptamethine cyanine PS for potential clinical applications.

Photoacoustic imaging of elevated glutathione in models of lung cancer for companion diagnostic applications.

Companion diagnostics (CDx) are powerful tests that can provide physicians with crucial biomarker information that can improve treatment outcomes by matching therapies to patients. Here, we report a photoacoustic imaging-based CDx (PACDx) for the selective detection of elevated glutathione (GSH) in a lung cancer model. GSH is abundant in most cells, so we adopted a physical organic chemistry approach to precisely tune the reactivity to distinguish between normal and pathological states. To evaluate the efficacy of PACDx in vivo, we designed a blind study where photoacoustic imaging was used to identify mice bearing lung xenografts. We also employed PACDx in orthotopic lung cancer and liver metastasis models to image GSH. In addition, we designed a matching prodrug, PARx, that uses the same SNAr chemistry to release a chemotherapeutic with an integrated PA readout. Studies demonstrate that PARx can inhibit tumour growth without off-target toxicity in a lung cancer xenograft model.

A multifunctional nano-delivery system enhances the chemo-co-phototherapy of tumor multidrug resistance via mitochondrial-targeting and inhibiting P-glycoprotein-mediated efflux.

Despite the excellent progress of chemotherapy and phototherapy in tumor treatment, their effectiveness on multidrug-resistant (MDR) tumors is still unsatisfactory. One of the main obstacles is drug efflux caused by P-glycoprotein in MDR cells. Herein, we developed a nano-delivery system that combines a P-glycoprotein inhibitor with chemotherapy and phototherapy to overcome MDR. Briefly, the system is prepared by the self-assembly of a ROS-triggered doxorubicin prodrug (PTD) and mitochondrial-targeted D-α-tocopherol polyethyleneglycol succinate (TPP-TPGS), in which a photoactive drug, IR780, is encapsulated (PTD/TT/IR780). PTD/TT/IR780 can target the release of TPP-TPGS, doxorubicin and IR780 at the mitochondrial site of MDR cells through ROS trigger. D-α-Tocopherol polyethyleneglycol succinate (TPGS) is a P-glycoprotein inhibitor, which will reduce the efflux of doxorubicin and IR780 from MDR cells. Under irradiation of an 808 nm near-infrared laser, IR780 generates heat and ROS, causing mitochondrial damage and prompting MDR cell apoptosis. At the same time, ROS can reduce the ATP content, which inhibits the P-glycoprotein function. In addition, an increase in the ROS generates positive feedback, allowing more nanoparticles to be cleaved and further promoting payload release in MDR cells, thereby enhancing the synergistic efficacy of chemotherapy and phototherapy. The in vitro cellular assay showed that PTD/TT/IR780 significantly inhibited MDR cell proliferation at a very low drug concentration (IC50 = 0.27 µg mL-1 doxorubicin-equivalent concentration). In vivo animal experiments based on BALB/c nude mice bearing MCF-7/ADR tumors confirmed a superior antitumor efficacy and an excellent biosafety profile. These findings demonstrate that this multifunctional nanoplatform provides a new approach for the treatment of MDR tumors.

A CORM loaded nanoplatform for single NIR light-activated bioimaging, gas therapy, and photothermal therapy in vitro.

Carbon monoxide (CO) can cause mitochondrial dysfunction, inducing apoptosis of cancer cells, which sheds light on a potential alternative for cancer treatment. However, the existing CO-based compounds are inherently limited by their chemical nature, such as high biological toxicity and uncontrolled CO release. Therefore, a nanoplatform - UmPF - that addresses such pain points is urgently in demand. In this study, we have proposed a nanoplatform irradiated by near-infrared (NIR) light to release CO. Iron pentacarbonyl (Fe(CO)5) was loaded in the mesoporous polydopamine layer that was coated on rare-earth upconverting nanoparticles (UCNPs). The absorption wavelength of Fe(CO)5 overlaps with the emission bands of the UCNPs in the UV-visible light range, and therefore the emissions from the UCNPs can be used to incite Fe(CO)5 to control the release of CO. Besides, the catechol groups, which are abundant in the polydopamine structure, serve as an ideal locating spot to chelate with Fe(CO)5; in the meantime, the mesoporous structure of the polydopamine layer improves the loading efficiency of Fe(CO)5 and reduces its biological toxicity. The photothermal effect (PTT) of the polydopamine layer is highly controllable by adjusting the external laser intensity, irradiation time and the thickness of the polydopamine layer. The results illustrate that the combination of CO gas therapy (GT) and polydopamine PTT brought by the final nanoplatform can be synergistic in killing cancer cells in vitro. More importantly, the possible toxic side effects can be effectively prevented from affecting the organism, since CO will not be released in this system without near-infrared light radiation.

An Activatable Near-Infrared Fluorescence Probe for in Vivo Imaging of Acute Kidney Injury by Targeting Phosphatidylserine and Caspase-3.

Renal-clearable and target-responsive near-infrared (NIR) fluorescent imaging probes have been promising for in vivo diagnosis of acute kidney injury (AKI). However, designing an imaging probe that is renal-clearable and concurrently responsive toward multiple molecular targets to facilitate early detection of AKI with improved sensitivity and specificity is challenging. Herein, by leveraging the receptor-mediated binding and retention effect along with enzyme-triggered fluorescence activation, we design and synthesize an activatable small-molecule NIR fluorescent probe (1-DPA2) using a "one-pot sequential click reaction" approach. 1-DPA2 can target both the externalized phosphatidylserine (PS) and active caspase-3 (Casp-3), two essential biomarkers of apoptosis, producing enhanced 808 nm NIR fluorescence and a high signal-to-background ratio (SBR) amenable to detecting the onset of cisplatin-induced AKI in mice as early as 24 h post-treatment with cisplatin. We not only monitor the gradual activation of Casp-3 in the kidney of mice upon AKI progression but also can report on the progressive recovery of kidney functions in AKI mice following N-acetyl-l-cysteine (NAC) therapy via real-time fluorescence imaging by 1-DPA2. This study demonstrates the ability of 1-DPA2 for longitudinal monitoring of renal cell apoptosis by concurrently targeting PS externalization and Casp-3 activation, which is efficient for early diagnosis of AKI and useful for prediction of potential drug nephrotoxicity as well as in vivo screening of anti-AKI drugs' efficacy.

Rodlike Particles of Polydopamine-CdTe Quantum Dots: An Actuator As a Photothermal Agent and Reactive Oxygen Species-Generating Nanoplatform for Cancer Therapy.

Herein, novel rodlike CdTe@MPA-PDA particles based on polydopamine (PDA) loaded with CdTe quantum dots (QDs) capped with mercaptopropionic acid (CdTe@MPA QDs) with atypical chemical features are evaluated as a potential actuator for photothermal therapy and oxidative stress induction. Under mild conditions established for the safe and efficient use of lasers, temperature increases of 10.2 and 7.8 °C, photothermal conversion efficiencies of 37.7 and 26.2%, and specific absorption rates of 99 and 69 W/g were obtained for CdTe@MPA-PDA and traditional PDA particles in water, respectively. The particles were set to interact with the human breast adenocarcinoma cell line MDA-MB-231. A significant cellular uptake with the majority of particles colocalized into the lysosomes was obtained at a concentration of 100 µg/mL after 24 h. Additionally, CdTe@MPA-PDA and CdTe@MPA QDs showed significantly different internalization levels and loading kinetics profiles. For the first time, the thermal lens technique was used to demonstrate the stability of particle-like CdTe@MPA-PDA after heating at pH 7 and their migration within the heating region due to the thermodiffusion effect. However, under acidic pH-type lysosomes, a performance decrease in heating was observed, and the chemical feature of the particles was damaged as well. Besides, the internalized rodlike CdTe@MPA-PDA notably enhanced the induction of oxidative stress compared with PDA alone and CdTe@MPA QDs in MDA-MB-231 cells initiating apoptosis. Combining these effects suggests that after meticulous optimizations of the conditions, the CdTe@MPA-PDA particles could be used as a photothermal agent under mild conditions and short incubation time, allowing cytoplasmatic subcellular localization. On the other hand, the same particles act as cell killers by triggering reactive oxygen species after a longer incubation time and lysosomal subcellular localization due to the pH effect on the chemical morphology features of the CdTe@MPA-PDA particles.

Nanomaterials for Targeted Delivery of Agrochemicals by an All-in-One Combination Strategy and Deep Learning.

The development of modern agriculture has prompted the greater input of herbicides, insecticides, and fertilizers. However, precision release and targeted delivery of these agrochemicals still remain a challenge. Here, a pesticide-fertilizer all-in-one combination (PFAC) strategy and deep learning are employed to form a system for controlled and targeted delivery of agrochemicals. This system mainly consists of three components: (1) hollow mesoporous silica (HMS), to encapsulate herbicides and phase-change material; (2) polydopamine (PDA) coating, to provide a photothermal effect; and (3) a zeolitic imidazolate framework (ZIF8), to provide micronutrient Zn2+ and encapsulate insecticides. Results show that the PFAC at concentration of 5 mg mL-1 reaches the phase transition temperature of 1-tetradecanol (37.5 °C) after 5 min of near-infrared (NIR) irradiation (800 nm, 0.5 W cm-2). The data of corn and weed are collected and relayed to deep learning algorithms for model building to realize object detection and further targeted weeding. In-field treatment results indicated that the growth of chicory herb was significantly inhibited when treated with the PFAC compared with the blank group after 24 h under NIR irradiation for 2 h. This system combines agrochemical innovation and artificial intelligence technology, achieves synergistic effects of weeding and insecticide and nutrient supply, and will potentially achieve precision and sustainable agriculture.

A dissipative pathway for the structural evolution of DNA fibres.

Biochemical networks interconnect, grow and evolve to express new properties as different chemical pathways are selected during a continuous cycle of energy consumption and transformation. In contrast, synthetic systems that push away from equilibrium usually return to the same self-assembled state, often generating waste that limits system recyclability and prevents the formation of adaptable networks. Here we show that annealing by slow proton dissipation selects for otherwise inaccessible morphologies of fibres built from DNA and cyanuric acid. Using single-molecule fluorescence microscopy, we observe that proton dissipation influences the growth mechanism of supramolecular polymerization, healing gaps within fibres and converting highly branched, interwoven networks into nanocable superstructures. Just as the growth kinetics of natural fibres determine their structural attributes to modulate function, our system of photoacid-enabled depolymerization and repolymerization selects for healed materials to yield organized, robust fibres. Our method provides a chemical route for error-checking, distinct from thermal annealing, that improves the morphologies and properties of supramolecular materials using out-of-equilibrium systems.

Stimuli-Responsive Metal-Organic Framework on a Metal-Organic Framework Heterostructure for Efficient Antibiotic Detection and Anticounterfeiting.

Stimuli-responsiveness is an important characteristic that show promising potential in various applications. Herein, a novel ZIF-8-on-Tb-dpn (H3dpn = 5-(2',4'-dicarboxylphenyl)nicotic acid) heterostructure is constructed using a heteroepitaxial strategy combining the chemical-responsive (antibiotics) and light-responsive behaviors. The pyridine nitrogen of Tb-dpn acts as an anchor site for Zn2+, which helps to overcome the limit of lattice mismatch between two metal-organic frameworks (MOFs) and promotes the growth of ZIF-8 nanocrystals. Based on the synergy effect of two MOFs, ZIF-8-on-Tb-dpn exhibits an efficient turn-off response toward tetracycline and chloramphenicol via competitive absorption, Förster resonance energy transfer, and photoinduced electron transfer processes with limit of detection values of 5.6 and 37.6 nM, respectively, which are three- to -fivefold lower than those of Tb-dpn. Moreover, the nanocage of ZIF-8 is utilized to encapsulate photochromic spiropyran (SP) molecules and realize the reversible conversion between SP and merocyanine (MC) under visible light and ultraviolet light. The MC form is accompanied with strong adsorption at 555 nm, which can erase the emission of Tb3+. Therefore, a reversible invisible anticounterfeiting pattern is designed with SP ⊂ ZIF-8-on-Tb-dpn for information anticounterfeiting. The excellent stimuli-responsive ability makes the luminescent platform a potential candidate in luminescence applications.

Survey of X-ray induced Cherenkov excited fluorophores with potential for human use.

X-ray induced molecular luminescence (XML) is a phenomenon that can be utilized for clinical, deep-tissue functional imaging of tailored molecular probes. In this study, a survey of common or clinically approved fluorophores was carried out for their megavoltage X-ray induced excitation and emission characteristics. We find that direct scintillation effects and Cherenkov generation are two possible ways to cause these molecules' excitation. To distinguish the contributions of each excitation mechanism, we exploited the dependency of Cherenkov radiation yield on X-ray energy. The probes were irradiated by constant dose of 6 MV and 18 MV X-ray radiation, and their relative emission intensities and spectra were quantified for each X-ray energy pair. From the ratios of XML, yield for 6 MV and 18 MV irradiation we found that the Cherenkov radiation dominated as an excitation mechanism, except for aluminum phthalocyanine, which exhibited substantial scintillation. The highest emission yields were detected from fluorescein, proflavin and aluminum phthalocyanine, in that order. XML yield was found to be affected by the emission quantum yield, overlap of the fluorescence excitation and Cherenkov emission spectra, scintillation yield. Considering all these factors and XML emission spectrum respective to tissue optical window, aluminum phthalocyanine offers the best XML yield for deep tissue use, while fluorescein and proflavine are most useful for subcutaneous or superficial use.

Rapid Ultrastructural Changes in the PSD and Surrounding Membrane after Induction of Structural LTP in Single Dendritic Spines.

The structural plasticity of dendritic spines is considered to be an important basis of synaptic plasticity, learning, and memory. Here, we induced input-specific structural LTP (sLTP) in single dendritic spines in organotypic hippocampal slices from mice of either sex and performed ultrastructural analyses of the spines using efficient correlative light and electron microscopy. We observed reorganization of the PSD nanostructure, such as perforation and segmentation, at 2-3, 20, and 120 min after sLTP induction. In addition, PSD and nonsynaptic axon-spine interface (nsASI) membrane expanded unevenly during sLTP. Specifically, the PSD area showed a transient increase at 2-3 min after sLTP induction. The PSD growth was to a degree less than spine volume growth at 2-3 min and 20 min after sLTP induction but became similar at 120 min. On the other hand, the nsASI area showed a profound and lasting expansion, to a degree similar to spine volume growth throughout the process. These rapid ultrastructural changes in PSD and surrounding membrane may contribute to rapid electrophysiological plasticity during sLTP.SIGNIFICANCE STATEMENT To understand the ultrastructural changes during synaptic plasticity, it is desired to efficiently image single dendritic spines that underwent structural plasticity in electron microscopy. We induced structural long-term potentiation (sLTP) in single dendritic spines by two-photon glutamate uncaging. We then identified the same spines at different phases of sLTP and performed ultrastructural analysis by using an efficient correlative light and electron microscopy method. We found that postsynaptic density undergoes dramatic modification in its structural complexity immediately after sLTP induction. Meanwhile, the nonsynaptic axon-spine interface area shows a rapid and sustained increase throughout sLTP. Our results indicate that the uneven modification of synaptic and nonsynaptic postsynaptic membrane might contribute to rapid electrophysiological plasticity during sLTP.

TPGS-Galactose-Modified Polydopamine Co-delivery Nanoparticles of Nitric Oxide Donor and Doxorubicin for Targeted Chemo-Photothermal Therapy against Drug-Resistant Hepatocellular Carcinoma.

The lack of cancer cell specificity and the occurrence of multidrug resistance (MDR) are two major obstacles in the treatment of hepatocellular carcinoma (HCC). To tackle these challenges, a novel nanoparticle (NP)-based drug delivery system (DDS) with a core/shell structure consisted of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)-galactose (Gal)/polydopamine (PDA) is fabricated. The NP is loaded with doxorubicin (DOX) and a nitric oxide (NO) donor N,N'-di-sec-butyl-N,N'-dinitroso-1,4-phenylenediamine (BNN) sensitive to heat to afford NO-DOX@PDA-TPGS-Gal. The unique binding of Gal to asialoglycoprotein receptor (ASGPR) and the pH-sensitive degradation of NP ensure the targeted transportation of NP into liver cells and the release of DOX in HCC cells. The near-infrared (NIR) light further facilitates DOX release and initiates NO generation from BNN due to the photothermal property of PDA. In addition to the cytotoxicity contributed by DOX, NO, and heat, TPGS and NO act as MDR reversal agents to inhibit P-glycoprotein (P-gp)-related efflux of DOX by HepG2/ADR cells. The combined chemo-photothermal therapy (chemo-PTT) by NO-DOX@PDA-TPGS-Gal thus shows potent anti-cancer activity against drug-resistant HCC cells in vitro and in vivo and significantly prolongs the life span of drug-resistant tumor-bearing mice. The present work provides a useful strategy for highly targeted and MDR reversal treatment of HCC.

Natural DNA assisted white light generation and stimuli responsive colour tuning.

The unique structure of a natural nucleic acid, calf thymus DNA, which can provide an appropriate scaffold for an efficient cascaded energy transfer among organic chromophores, has been used for the generation of bright and pure white light on UV light excitation. Two most commonly used DNA stains, 4',6-diamidino-2-phenylindole (DAPI) and ethidium bromide (EB) have been used as a part of the donor-acceptor pairs. We have judiciously selected 10-anthracene-10-yl-3-methylbenzothiazol-3-ium chloride (AnMBTZ), an ultrafast molecular rotor, to act as a bridge between DNA bound DAPI and EB for the cascaded flow of energy. The unique molecular rotor properties of AnMBTZ and its exceptional binding ability with natural DNA help to form a distinct tri-chromophoric system in DNA template which can produce bright and pure white light on UV excitation. Detailed flow of energy from photoexcited DAPI to EB via AnMBTZ has been explored using steady state and time-resolved emission spectroscopy. Further, unique binding nature of AnMBTZ with DNA molecules has been used to modulate the colour of the emission from the present tri-chromophoric system by external stimuli, like salt and temperature. Such unique stimuli responsive multi-chromophoric system in a bio-template has great potential for different lightening applications.

Mussel-Inspired Immobilization of Photocatalysts with Synergistic Photocatalytic-Photothermal Performance for Water Remediation.

The serious problem of pharmaceutical and personal care product pollution places great pressure on aquatic environments and human health. Herein, a novel coating photocatalyst was synthesized by adhering Ag-AgCl/WO3/g-C3N4 (AWC) nanoparticles on a polydopamine (PDA)-modified melamine sponge (MS) through a facile layer-by-layer assembly method to degrade trimethoprim (TMP). The formed PDA coating was used for the anchoring of nanoparticles, photothermal conversion, and hydrophilic modification. TMP (99.9%; 4 mg/L) was removed in 90 min by the photocatalyst coating (AWC/PDA/MS) under visible light via a synergistic photocatalytic-photothermal performance route. The stability and reusability of the AWC/PDA/MS have been proved by cyclic experiments, in which the removal efficiency of TMP was still more than 90% after five consecutive cycles with a very little mass loss. Quantitative structure-activity relationship analysis revealed that the ecotoxicities of the generated intermediates were lower than those of TMP. Furthermore, the solution matrix effects on the photocatalytic removal efficiency were investigated, and the results revealed that the AWC/PDA/MS still maintained excellent photocatalytic degradation efficiency in several actual water and simulated water matrices. This work develops recyclable photocatalysts for the potential application in the field of water remediation.

Novel Multifunctional Stimuli-Responsive Nanoparticles for Synergetic Chemo-Photothermal Therapy of Tumors.

In this study, a novel class of multifunctional responsive nanoparticles is designed and fabricated as drug nanocarriers for synergetic chemo-photothermal therapy of tumors. The proposed nanoparticles are composed of a thermo-/pH-responsive poly(N-isopropylacrylamide-co-acrylic acid) (PNA) nanogel core, a polydopamine (PDA) layer for photothermal conversion, and an outer folic acid (FA) layer as a targeting agent for the folate receptors on tumor cells. The fabricated nanoparticles show good biocompatibility and outstanding photothermal conversion efficiency. The proposed nanoparticles loaded with doxorubicin (DOX) drug molecules are stable under physiological conditions with low leakage of drugs, while rapidly release drugs in environments with low pH conditions and at high temperature. The experimental results show that the drug release process is mainly governed by Fickian diffusion. In vitro cell experimental results demonstrate that the PNA-DOX@PDA-FA nanoparticles can be phagocytized by 4T1 tumor cells and release drugs in tumor cell acidic environments, and confirm that the combined chemo and photothermal therapeutic efficacy of PNA-DOX@PDA-FA nanoparticles is higher than the photothermal therapeutic efficacy or the chemotherapeutic efficacy alone. The proposed multifunctional responsive nanoparticles in this study provide a novel class of drug nanocarriers as a promising tool for synergetic chemo-photothermal therapy of tumors.

Near-Infrared Photothermal/Photodynamic-in-One Agents Integrated with a Guanidinium-Based Covalent Organic Framework for Intelligent Targeted Imaging-Guided Precision Chemo/PTT/PDT Sterilization.

Phototherapy holds great promise in the treatment of bacterial infections, especially the multidrug resistant bacterial infections. However, most therapeutic agents are based on the integration of individual photothermal agents and photosensitizers, always in the activated state, and generally lack bacterial specificity, resulting in uncertain pharmacokinetics and serious nonspecific damage to normal tissues. Herein, we report a pH-responsive nanoplatform with synergistic chemo-phototherapy function for smart fluorescence imaging-guided precision sterilization. pH reversible activated symmetric cyanine was designed and prepared as a bacterial-specific imaging unit and PTT/PDT-in-one agent. Meanwhile, a guanidinium-based covalent organic framework (COF) was employed as a nanocarrier and chemotherapy agent to build the intelligent nanoplatform via electrostatic self-assembly. The self-assembly of the PTT/PDT-in-one agent and the COF greatly improves the stability and blood circulation of the PTT/PDT-in-one agent and provides charge-reversed intelligent targeting ability. The developed smart nanoplatform not only enables bacterial-targeted imaging but also possesses chemo/PTT/PDT synergetic high-efficiency bactericidal effects with little side effects, showing great potential in practical applications.

Novel pH-Triggered Doxorubicin-Releasing Nanoparticles Self-Assembled by Functionalized ß-Cyclodextrin and Amphiphilic Phthalocyanine for Anticancer Therapy.

Cyclodextrins (CDs), as pharmaceutical excipients with excellent biocompatibility, non-immunogenicity, and low toxicity in vivo, are widely used to carry drugs by forming inclusion complexes for improving the solubility and stability of drugs. However, the limited space of CDs' lipophilic central cavity affects the loading of many drugs, especially with larger molecules. In this study, ß-CDs were modified by acetonization to improve the affinity for the chemotherapy drug doxorubicin (DOX), and doxorubicin-adsorbing acetalated ß-CDs (Ac-CD:DOX) self-assembled to nanoparticles, followed by coating with the amphiphilic zinc phthalocyanine photosensitizer ZnPc-(PEG)5 for antitumor therapy. The final product ZnPc-(PEG)5:Ac-CD:DOX was demonstrated to have excellent stability and pH-sensitive drug release characteristics. The cell viability and apoptosis assay showed synergistic cytotoxic effects of chemotherapy and phototherapy. The mechanism of cytotoxicity was analyzed in terms of intracellular reactive oxygen species, mitochondrial membrane potential, and subcellular localization. More importantly, in vivo experiments indicated that ZnPc-(PEG)5:Ac-CD:DOX possessed significant tumor targeting, prominent antitumor activity, and less side effects. Our strategy expands the application of CDs as drug carriers and provides new insights into the development of CD chemistry.

68Ga-Labeled Magnetic-NIR Persistent Luminescent Hybrid Mesoporous Nanoparticles for Multimodal Imaging-Guided Chemotherapy and Photodynamic Therapy.

Featured with a zero-autofluorescence background, superior signal-to-noise ratio, high sensitivity, and deep penetration ability, near-infrared persistent luminescence nanoparticle (NIR-PLNP)-based multimodal nanoprobes show great potential for full-scale noninvasive cancer diagnosis. However, direct synthesis of NIR-PLNP-based multimodal nanoprobes with high drug loading capacity to meet growing cancer theranostic demands remains a challenge. In this work, multifunctional hybrid mesoporous nanoparticles (HMNPs) that integrate NIR-PLNPs (Ga2O3:Cr3+, Nd3+), magnetic nanoparticles (Gd2O3), and radionuclides (68Ga) are designed and constructed via a large-pore (mesoporous silica nanoparticle) MSN-templated strategy. The ingenious composition design endows HMNPs with rechargeable NIR-PL, superior longitudinal relaxivity, and excellent radioactivity, making these versatile nanoparticles available for long-term in vivo NIR-PL imaging, magnetic resonance imaging (MRI), and positron emission tomography (PET) imaging. More importantly, the application of large-pore MSN templates maintains the mesoporous structure of HMNPs, promising excellent drug loading capacity of these nanoparticles. As a proof-of-concept, HMNPs loaded with a high dose of DOX (chemotherapy agent) and Si-Pc (photosensitizer) are rationally designed for chemotherapy and NIR-PL-sensitized photodynamic therapy (PDT), respectively. Studies with mice tumor models demonstrate that the DOX/Si-Pc-loaded HMNPs possess excellent cancer cell killing ability and an outstanding tumor suppression effect without systemic toxicity. This work shows the great potential of HMNPs as an "all-in-one" nanotheranostic tool for multimodal NIR-PL/MR/PET imaging-guided chemotherapy and NIR-PL-sensitized photodynamic cancer therapy and provides an innovative paradigm for the development of NIR-PLNP-based nanoplatforms in cancer theranostic.

Effect of ultrasonic frequency and power on the sonodynamic therapy activity of cationic Zn(II) phthalocyanines.

We report on the sonodynamic activity of cationic phthalocyanines (Pcs) and the effect of the variation of two parameters: ultrasound frequency and power (Par I (1 MHz, 1 W cm-2), Par II (1 MHz, 2 W cm-2), Par III (3 MHz, 1 W cm-2) and Par IV (3 MHz, 2 W cm-2)) on the efficiency of their reactive oxygen species generation and cancer eradication in vitro thereof. Where Par stands for the various combinations of these parameters. Four Pcs were investigated with substituents bearing diethylamine, ortho- and para-pyridine and morpholine groups. Overall, the para-pyridine and morpholine Pcs showed substantial sono-activity in the various ultrasound parameters with Par I and IV generally showing better singlet oxygen and hydroxyl radicals generation confirmed by electron paramagnetic resonance spectroscopy. In some cases, very high hydroxyl radicals' generation was observed at Par II. Furthermore, the fragmentation of the Pcs after Par II treatments was confirmed using UV-vis and magnetic circular dichroism spectroscopy. The reactive species generation efficacy decreased at Par III for all samples. Ultrasound assisted cytotoxicity of the Pcs was confirmed in vitro using the human (Michigan Cancer Foundation-7) breast cancer cell line.

Facile Synthesis of Cyclic Peptide-Phthalocyanine Conjugates for Epidermal Growth Factor Receptor-Targeted Photodynamic Therapy.

A facile procedure for in situ peptide cyclization and phthalocyanine conjugation was developed by utilizing a bifunctional linker incorporated with a bis(bromomethyl)benzene unit and a cyclopentadiene moiety. These functional groups facilitated the nucleophilic substitution with the two cysteine residues of the linear peptides followed by the Diels-Alder reaction with the maleimide moiety attached to a zinc(II) phthalocyanine. With this approach, three cyclic peptide-phthalocyanine conjugates were prepared in 20-26% isolated yield via a one-pot procedure. One of the conjugates containing a cyclic form of the epidermal growth factor receptor (EGFR)-binding peptide sequence CMYIEALDKYAC displayed superior features as an advanced photosensitizer. It showed preferential uptake by two EGFR-positive cancer cell lines (HT29 and HCT116) compared with two EGFR-negative counterparts (HeLa and HEK293), resulting in significantly higher photocytotoxicity. Intravenous administration of this conjugate into HT29 tumor-bearing nude mice resulted in selective localization in tumor and effective inhibition of tumor growth upon photodynamic treatment.