Amphiphilic Dye Research Articles

Self-Assembly of a Perfluorinated Amphiphilic Cyanine Dye into Branched Tubular J-Aggregates.

The self-assembly process is governed by the individual constituents of molecules through precise non-covalent interactions. Amphiphilic cyanines are intriguing in supramolecular chemistry due to the large polarizability of their delocalized π-electron systems, their tuneable optical properties and their ability to form well-defined self-assembled structures in different media. Here we present the synthesis of a novel tetrahydroxy amphiphilic carbocyanine dye with perfluoro alkylated chains -(CH2)2-(CF2)5-CF3 as hydrophobic segments and aminoproanediol as hydrophilic segment. The target molecule was synthesized in a multi-step process, which illustrates the complexity and precision required to achieve the desired structure. This study focuses on the comparison of the influence of C8H17 and C8H4F13 tails and the effects of carboxylated and non-ionic aminopropanediol head groups as substituents on self-assembly of the TBC dye. Absorption and fluorescence measurements show similar spectroscopic properties to cyanine dyes studied previously. Cryogenic transmission electron microscopy (cryo-TEM) reveals formation of multiple supramolecular aggregates. As supramolecular assembly is very sensitive to sample preparation, multilamellar or multivesicular vesicles are obtained preferentially in vigorously vortexed solutions. Moreover, time-dependent tube formation was observed in gently mixed solutions. Thereby, we could follow the growing mechanism of the unprecedented Y-junctions of supramolecular tubes.

Self-Assembly of Metallo-Supramolecular Amphiphiles based on Azadipyrromethenes: Consecutive Pathways to Nanodiscs and Nanosheets.

A new class of metallo-supramolecular amphiphilic dyes 1 a, b was constructed by using two azadipyrromethene units which were respectively modified with two hydrophobic alkyl and two hydrophilic oligo(ethylene glycol) chains. The spectroscopic and morphological studies revealed the consecutive self-assembly pathways of 1 a in EtOH/H2O mixed solvent. The monomers of 1 a firstly aggregated into the kinetic-controlled, nanodisc-shaped Agg. I upon cooling and the latter spontaneously transformed into the thermodynamically more stable Agg. II with a nanosheet morphology. While the non-fluorescent Agg. I displayed a broad absorption band (λmax=615 nm), the Agg. II displayed a more intensive and narrowed J-band (λmax=693 nm) and a fluorescence band with a maximum at 760 nm (Φfl=0.1), which could be ascribed to the J-aggregation induced emission enhancement. The kinetics of Agg. I to Agg. II transformation was further modulated by seed-initiated supramolecular polymerization with various ratios of Seedagg.II, in which the transformation rate was significantly increased by ca. 2 orders of magnitude compared to the spontaneous process. The supramolecular amphiphile 1 b bearing longer hydrophilic chains formed only one type aggregate, which exhibited spectroscopic and morphological properties that were highly comparable with that of Agg. I.

Novel BODIPY-based nano-biomaterials with enhanced D-A-D structure for NIR-triggered photodynamic and photothermal therapy

Near‐infrared (NIR) responsive nanoparticles are an important platform for multimodal phototherapy. Importantly, the simultaneous NIR-triggered photodynamic (PDT) and photothermal (PTT) therapy is a powerful approach to increase the antitumor efficiency of phototherapic nanoparticles due to the synergistic effect. Herein, a boron dipyrromethene (BODIPY)-based amphiphilic dye with enhanced electron donor–acceptor-donor (D-A-D) structure (BDP-AP) was designed and synthesized, which could self-assemble into stable nanoparticles (BDP-AP NPs) for the synergistic NIR-triggered PDT/PTT therapy. BDP-AP NPs synchronously generated singlet oxygen (1O2) and achieved preeminent photothermal conversion efficiency (61.42%). The in vitro and in vivo experiments showed that BDP-AP NPs possessed negligible dark cytotoxicity and infusive anticancer performance. BDP-AP NPs provide valuable guidance for the construction of PDT/PTT-synergistic NIR nanoagents to improve the efficiency of photoinduced cancer therapy in the future.

Control of Kinetic Pathways toward Supramolecular Chiral Polymorphs for Tunable Circularly Polarized Luminescence.

An amphiphilic aza-BODIPY dye (S)-1 bearing two chiral hydrophilic side chains with S-stereogenic centers was synthesized. This dye exhibited kinetic-controlled self-assembly pathways and supramolecular chiral polymorphism properties in MeOH/H2O (9/1, v/v) mixed solvent. The (S)-1 monomers first aggregated into a kinetic controlled, off-pathway species Agg. A, which was spontaneously transformed into an on-pathway metastable aggregate (Agg. B) and subsequently into the thermodynamic Agg. C. The three aggregate polymorphs of dye (S)-1 displayed distinct optical properties and nanomorphologies. In particular, chiral J-aggregation characteristics were observed for both Agg. B and Agg. C, such as Davydov-split absorption bands (Agg. B), extremely sharp and intense J-band with large bathochromic shift (Agg. C), non-diminished fluorescence upon aggregation, as well as strong bisignated Cotton effects. Moreover, the AFM and TEM studies revealed that Agg. A had the morphology of nanoparticle while fibril or rod-like helical nanostructures with left-handedness were observed respectively for Agg. B and Agg. C. By controlling the kinetic transformation process from Agg. B to Agg. C, thin films consisting of Agg. B and Agg. C with different ratios were prepared, which displayed tunable CPL with emission maxima at 788-805 nm and g-factors between -4.2×10-2 and -5.1×10-2.

Benefits of Combined Fluorescence Lifetime Imaging Microscopy and Fluorescence Correlation Spectroscopy for Biomedical Studies Demonstrated by Using a Liposome Model System

Drug delivery systems play a pivotal role in targeted pharmaceutical transport and controlled release at specific sites. Liposomes, commonly used as drug carriers, constitute a fundamental part of these systems. Moreover, the drug–liposome model serves as a robust platform for investigating interaction processes at both cellular and molecular levels. To advance our understanding of drug carrier uptake mechanisms, we employed fluorescence lifetime imaging microscopy (FLIM) and fluorescence correlation spectroscopy (FCS), leveraging the unique benefits of two-photon (2P) excitation. Our approach utilized giant unilamellar vesicles (GUVs) as a simplified model system for cell membranes, labelled with the amphiphilic fluorescent dye 3,3′-dioctadecyloxa-carbocyanine (DiOC18(3)). Additionally, large unilamellar vesicles (LUVs) functioned as a drug carrier system, incorporating the spectrally distinct fluorescent sulforhodamine 101 (SRh101) as a surrogate drug. The investigation emphasized the diverse interactions between GUVs and LUVs based on the charged lipids employed. We examined the exchange kinetics and structural alterations of liposome carriers during the uptake process. Our study underscores the significance of employing 2P excitation in conjunction with FLIM and FCS. This powerful combination offers a valuable methodological approach for studying liposome interactions, positioning them as an exceptionally versatile model system with a distinct technical advantage.

Molecular engineering of fluorescent dyes for long-term specific visualization of the plasma membrane based on alkyl-chain-regulated cell permeability

Long-term visualization of changes in plasma membrane dynamics during important physiological processes can provide intuitive and reliable information in a 4D mode. However, molecular tools that can visualize plasma membranes over extended periods are lacking due to the absence of effective design rules that can specifically track plasma membrane fluorescent dye molecules over time. Using plant plasma membranes as a model, we systematically investigated the effects of different alkyl chain lengths of FMR dye molecules on their performance in imaging plasma membranes. Our findings indicate that alkyl chain length can effectively regulate the permeability of dye molecules across plasma membranes. The study confirms that introducing medium-length alkyl chains improves the ability of dye molecules to target and anchor to plasma membranes, allowing for long-term imaging of plasma membranes. This provides useful design rules for creating dye molecules that enable long-term visualization of plasma membranes. Using the amphiphilic amino-styryl-pyridine fluorescent skeleton, we discovered that the inclusion of short alkyl chains facilitated rapid crossing of the plasma membrane by the dye molecules, resulting in staining of the cell nucleus and indicating improved cell permeability. Conversely, the inclusion of long alkyl chains hindered the crossing of the cell wall by the dye molecules, preventing staining of the cell membrane and demonstrating membrane impermeability to plant cells. The FMR dyes with medium-length alkyl chains rapidly crossed the cell wall, uniformly stained the cell membrane, and anchored to it for a long period without being transmembrane. This allowed for visualization and tracking of the morphological dynamics of the cell plasma membrane during water loss in a 4D mode. This suggests that the introduction of medium-length alkyl chains into amphiphilic fluorescent dyes can transform them from membrane-permeable fluorescent dyes to membrane-staining fluorescent dyes suitable for long-term imaging of the plasma membrane. In addition, we have successfully converted a membrane-impermeable fluorescent dye molecule into a membrane-staining fluorescent dye by introducing medium-length alkyl chains into the molecule. This molecular engineering of dye molecules with alkyl chains to regulate cell permeability provides a simple and effective design rule for long-term visualization of the plasma membrane, and a convenient and feasible means of chemical modification for efficient transmembrane transport of small molecule drugs.

Differences in Lipid Order and Dynamics in Plasma Membranes Assessed by Nonlinear Optical Microscopy.

When amphiphilic polar dyes were added to the cells, they intercalated predominantly in the outer leaf of the plasma membrane, making them active for second harmonic generation (SHG). The fluorescence of the dye enabled simultaneous 3D imaging of SHG and two-photon excited fluorescence (TPF). Because SHG intensity is sensitive to the alignment of the dyes, which reflects lipid ordering in the plasma membrane, we assessed the difference in lipid ordering by comparing the SHG intensity normalized to the TPF intensity. Together with an enzyme release assay that detects pore formation in the plasma membrane, our SHG assay revealed how polycations affect lipid ordering at low concentrations, where membrane damage has not yet been examined. By scaling the results of the assays with the charge concentration of the two polycations, polyethylenimine (PEI) and poly-l-lysine (PLL), we found that PEI reduced the lipid order more than PLL, and PLL formed more pores than PEI. A comparison of the SHG and TPF images of the wounded cells revealed that one of the lipid dynamics (flip-flop) was significantly enhanced in the bleb membrane. Moreover, the SHG assay indicated that the biocompatible polymer, poly(N-(2-hydroxypropyl)methacrylamide), did not affect the lipid order. Thus, our technique allows the assessment of the plasma membrane structure at the molecular level.

Near-atomic-resolution structure of J-aggregated helical light-harvesting nanotubes.

Cryo-electron microscopy has delivered a resolution revolution for biological self-assemblies, yet only a handful of structures have been solved for synthetic supramolecular materials. Particularly for chromophore supramolecular aggregates, high-resolution structures are necessary for understanding and modulating the long-range excitonic coupling. Here, we present a 3.3 Å structure of prototypical biomimetic light-harvesting nanotubes derived from an amphiphilic cyanine dye (C8S3-Cl). Helical 3D reconstruction directly visualizes the chromophore packing that controls the excitonic properties. Our structure clearly shows a brick layer arrangement, revising the previously hypothesized herringbone arrangement. Furthermore, we identify a new non-biological supramolecular motif-interlocking sulfonates-that may be responsible for the slip-stacked packing and J-aggregate nature of the light-harvesting nanotubes. This work shows how independently obtained native-state structures complement photophysical measurements and will enable accurate understanding of (excitonic) structure-function properties, informing materials design for light-harvesting chromophore aggregates.

Structure affinity of the Langmuir monolayer and the corresponding Langmuir-Blodgett film revealed by X-ray techniques.

The possibility of reproducing the structural organization and functional abilities of a Langmuir monolayer in a film formed from it is one of the fundamental problems of ultrathin film science. This work is devoted to the comparison of monolayer and Langmuir-Blodgett (LB) film characteristics using the example of 2D systems based on the dithia-aza-crown substituted hemicyanine dye HCS. As was shown earlier, the investigated systems are promising for the preparation of selective sensors and extractors for mercury ions in aqueous solutions with a subnanomolar sensitivity threshold. Therefore, the study of the analyte binding mechanism by such a film is of great importance. The study carried out using an ultra-highly brilliant X-ray source (ESRF) allows the application of highly sensitive techniques such as X-ray reflectometry (XRR) and X-ray standing wave (XSW). Comparison of the electron density depth profile of the HCS Langmuir monolayer at the air/water interface and the HCS film transferred to a silicon substrate shows the preservation of the film structure and its functional features. The XSW measurements in turn reveal the similarities in the fine structure of preorganized Langmuir monolayers and Langmuir-Blodgett films of HCS. The integration of X-ray techniques with molecular modeling methods allowed us to show that the crown-ether groups of HCS molecules in the pre-organized monolayer and in the corresponding LB film lie on the surface of water or silicon, and the bound mercury ion is located above the crown-ether, partially binding to the nitrogen atom. The latter loses conjugation to the chromophore group, thereby altering the UV-vis spectrum and providing a response signal. The revealed mechanism of imprinting preorganization allows the proposed approach to be extended to other crown-substituted amphiphilic dyes to significantly enhance the sensory response.

Growth of Merocyanine Dye J-Aggregate Nanosheets by Living Supramolecular Polymerization.

J-aggregates are highly desired dye aggregates but so far there has been no general concept how to accomplish the required slip-stacked packing arrangement for dipolar merocyanine (MC) dyes whose aggregation commonly affords one-dimensional aggregates composed of antiparallel, co-facially stacked MCs with H-type coupling. Herein we describe a strategy for MC J-aggregates based on our results for an amphiphilic MC dye bearing alkyl and oligo(ethylene glycol) side chains. In an aqueous solvent mixture, we observe the formation of two supramolecular polymorphs for this MC dye, a metastable off-pathway nanoparticle showing H-type coupling and a thermodynamically favored nanosheet showing J-type coupling. Detailed studies concerning the self-assembly mechanism by UV-Vis spectroscopy and the packing structure by atomic force microscopy and wide-angle X-ray scattering show how the packing arrangement of such amphiphilic MC dyes can afford slip-stacked two-dimensional nanosheets whose macrodipole is compensated by the formation of a bilayer structure. As an additional feature we demonstrate how the size of the nanosheets can be controlled by seeded living supramolecular polymerization.

Growth of Merocyanine Dye J‐Aggregate Nanosheets by Living Supramolecular Polymerization

AbstractJ‐aggregates are highly desired dye aggregates but so far there has been no general concept how to accomplish the required slip‐stacked packing arrangement for dipolar merocyanine (MC) dyes whose aggregation commonly affords one‐dimensional aggregates composed of antiparallel, co‐facially stacked MCs with H‐type coupling. Herein we describe a strategy for MC J‐aggregates based on our results for an amphiphilic MC dye bearing alkyl and oligo(ethylene glycol) side chains. In an aqueous solvent mixture, we observe the formation of two supramolecular polymorphs for this MC dye, a metastable off‐pathway nanoparticle showing H‐type coupling and a thermodynamically favored nanosheet showing J‐type coupling. Detailed studies concerning the self‐assembly mechanism by UV‐Vis spectroscopy and the packing structure by atomic force microscopy and wide‐angle X‐ray scattering show how the packing arrangement of such amphiphilic MC dyes can afford slip‐stacked two‐dimensional nanosheets whose macrodipole is compensated by the formation of a bilayer structure. As an additional feature we demonstrate how the size of the nanosheets can be controlled by seeded living supramolecular polymerization.

Label-free multimodal analysis of copper ions at below permissible exposure limit in the aqueous medium

An anthraimidazoledione based amphiphilic dye molecule was synthesized that shows formation of tuneable charge-transfer state in solution, susceptible to change in pH, polarity and hydrogen bonding ability of the medium. The compound also showed formation of nanoscopic self-assembled structure in water medium. The probe molecule can achieve multimodal detection (colorimetric, fluorimetric and electrochemical) of copper ions as low as 0.3 ppm in the aqueous medium. Addition of copper leads to dose-dependent ratiometric change in solution color from yellow to purple. The mechanistic investigation indicates that the coordination of copper ions was possible via simultaneous engagement of both imidazole nitrogen ends and neighbouring hydroxyl unit. Not only optical property, the changes in microenvironment also influence the selectivity as well as sensitivity of the probe molecule towards Cu2+ ions. Further, the optical probe is used for detection as well as quantification of copper ions in natural water samples without any sample pretreatment. Low-cost, reusable paper strips are developed for rapid, on-location detection of residual Cu2+ in real-life samples.

Multimodal Sensing of Acetate Anion by Using Anthraimidazoledione‐Based Redox‐Active Amphiphilic Dye in Aqueous Environment

AbstractAnthraimidazoledione based amphiphilic dye is synthesized that exhibits pH‐responsive chromogenic response in aqueous environment. This entices us to investigate its anion‐responsive behavior. In pure water, the compound shows no optical response towards anions (poor sensitivity), whereas interaction with multiple anions is witnessed in acetonitrile medium (poor selectivity). Interestingly, changes in solution color from yellow to orange is observed explicitly upon addition of acetate anion, accompanied by fluorescence turn‐off response. Further, it is revealed that the acetate engaged in hydrogen bonding interaction with both imidazole −NH group and hydroxyl unit. The high basicity of acetate anion along with ‘Y‐shaped’ structure might be responsible for such unique selectivity. The present system has been involved in analyzing residual acetate in natural water samples. Low‐cost, reusable paper strips have been designed for equipment free, rapid on‐location detection of acetate.

An amphiphilic near-infrared Mn,O-chelated metallo-azadipyrromethene dye: Synthesis, acid-responsive properties, and aggregation pathway control

A new amphiphilic Mn,O-chelated azadipyrromethene dye 1 bearing dodecyl chains at the 1,7-phenyls and oligo(ethylene glycol) chains at the 3,5-phenyls was synthesized and characterized. The dye 1 exhibited an absorption maximum in NIR at 823 nm, which is largely bathochromically shifted as compared with the known aza-BODIPY as well as the B,O-chelated aza-BODIPY dyes. Meanwhile, the electrochemical studies of this dye indicated a lower HOMO-LUMO gap in comparison with the boron-chelated analogues. This dye also displayed the acid-responsive properties, as indicated by the hypsochromical shift of ca. 94 nm of the absorption band as well as the occurrence of fluorescence emission at 751 nm upon adding trifluoroacetic acid (TFA) into the dye 1 solution. Moreover, in highly polar solvent MeOH the amphiphilic dye 1 self-assembled into H-type aggregates, which exhibited a fibrous morphology in AFM studies. Further temperature-dependent UV/Vis absorption spectroscopic studies revealed a cooperative aggregation mechanism of dye 1 in MeOH. Based on the acid-responsive properties of 1, a method of control of the aggregation pathway of dye 1 by using acid and base was proposed and demonstrated by UV/Vis spectroscopic studies.

Lipophilic Anchors that Embed Bioconjugates in Bilayer Membranes: A Review.

A wide range of biomaterials and engineered cell surfaces are composed of bioconjugates embedded in liposome membranes, surface-immobilized bilayers, or the plasma membranes of living cells. This review article summarizes the various ways that Nature anchors integral and peripheral proteins in a cell membrane and describes the strategies devised by chemical biologists to label a membrane protein in living cells. Also discussed are modern synthetic and semisynthetic methods to produce lipidated proteins. Subsequent sections describe methods to anchor a three-component synthetic construct that is composed of a lipophilic membrane anchor, hydrophilic linker, and exposed functional component. The surface exposed payload can be a fluorophore, aptamer, oligonucleotide, polypeptide, peptide nucleic acid, polysaccharide, branched dendrimer, or linear polymer. Hydrocarbon chains are commonly used as the membrane anchor, and a general experimental trend is that a two chain lipid anchor has higher membrane affinity than a cholesteryl or single chain lipid anchor. Amphiphilic fluorescent dyes are effective molecular probes for cell membrane imaging and a zwitterionic linker between the fluorophore and the lipid anchor promotes high persistence in the plasma membrane of living cells. A relatively new advance is the development of switchable membrane anchors as molecular tools for fundamental studies or as technology platforms for applied biomaterials.

Modulating nanostructure morphology and mesomorphic properties using unsaturation in cardanol-azo benzenes.

Herein, we report the synthesis and self-assembly of a new class of amphiphilic azo dyes derived from a plant-based phenol, cardanol. Analysis of the self-assembly of these new azo derivatives was intriguing, and they exhibit some unique nanostructures, such as bicelles and microgel-like structures, and smectic-type thermotropic mesophases.

Efficient removal of rhodamine B and methylene blue from water using polyurethane based porous material

AbstractHere the thermally catalyzed azide‐alkyne click reaction was invoked for synthesis of functional triazole. The formed triazole was invoked to engineer polyurethane as water immiscible material. The synthesized functional triazole and polyurethane were well characterized using spectroscopic techniques—nuclear magnetic resonance (NMR), electrospray ionization mass spectrum (ESI MS), and attenuated total reflectance Fourier transform infrared (ATR‐FTIR) accordingly. The N2 adsorption–desorption isotherms confirmed the material to be mesoporous in nature with a surface area of 12.89 m2/g, pore volume of 0.085 cc/g, and pore radius of 7.14 nm. The characterized triazole material can be crucial with properties related to antifungal responses and UV absorption. The polyurethane material showed adsorption of amphiphilic dye—rhodamine (RH B) and methylene blue (MB). It was selective to release of rhodamine B (RH B) quite efficiently. The recycling of polyurethane reported up to cycle four revealed efficient adsorption‐release.

Amphiphilic Rhodamine Nano-assembly as a Type I Supramolecular Photosensitizer for Photodynamic Therapy

Photodynamic therapy (PDT) is a promising clinical method for treating a wide range of cancers. Recently, PDT employing type I photosensitizers (PSs) has attracted considerable attention owing to the feasibility of efficient PDT under hypoxic conditions. Particularly, type I supramolecular PSs (SPSs) are promising candidates owing to their functional extensibility by facile hybridization. However, type I SPSs are rare, and the development strategy has not been established yet. In this work, we demonstrated that supramolecular assembly of a simple amphiphilic rhodamine 19 (Rh19-MA-C18) functioned as a type I SPS and exhibited significant PDT effect on cancer cells and cancer-bearing mice. This work demonstrates the potential of supramolecular nano-assembly composed of an amphiphilic rhodamine dye as an efficient type I SPS.

In-vitro study for Ibuprofen encapsulation, controlled release and cytotoxicity improvement using excipient-drugs mixed micelle

The dye-drug combinations are widely used in pharmaceutics, but as a mixed micelle, little attention has been dedicated to improving poorly water-soluble pharmaceuticals and cytotoxicity in the pharmaceutical and biotechnology industries. This study examined the influence of amphiphilic dyes and medicines in aqueous media. Anionic tartrazine (TAZ) was combined with cationic diphenhydramine hydrochloride (DPC) and cetirizine hydrochloride (CTZ) to form mixed micelles. As revealed by the mixed micelles of TAZ-DPC and TAZ-CTZ, TAZ and DPC/CTZ exhibited a more pronounced synergistic relationship. Mixed micelles increased the binding constant (LogKb) of the anti-inflammatory Ibuprofen (IBF) drug by raising the αTAZ 0.0–1.0 in the aqueous environment. At a very high mole fraction of αTAZ 0.99, the highest LogKb values attained were 4.3 and 4.1. The present study used molecular docking to portray IBF's interaction with TAZ, DPC, CTZ, and TAZ-DPC and TAZ-CTZ combinations. Electrostatic contact made IBF more bound in TAZ and TAZ-DPC mixtures. TAZ-DPC had better encapsulation efficiency (%EE) than TAZ-CTZ at αTAZ 0.9, indicating an electrostatic interaction between IBF and TAZ rich mixed micelles. After 50 h, the controlled release of IBF in PBS at pH 7.4 was about 46% from both mixed micelles. Furthermore, with αTAZ 0.9 at 25 mmolL−1, cell viability in TAZ-DPC and TAZ-CTZ mixed micelles was increased by 78% and 72%, respectively, in the presence of IBF. Increasing TAZ concentrations may have reduced IBF cytotoxicity as seen by the enhanced cell viability. The current study also showed that cytotoxicity could be decreased and the number of excipients in a drug delivery system could be decreased by combining pharmaceuticals with amphiphilic dye.

Self-assembled boron dipyrromethene-based nanocarriers with encapsulated doxorubicin for chemo-photodynamic therapy

The development of water-soluble boron dipyrromethene (BODIPY) dyes is important for biomedical applications as it offers the potential to form a drug self-delivery system with superior drug utilization. Herein, the amphiphilic BODIPY dye NBDP with good water solubility and superior onsite singlet oxygen generation ability was obtained, in which the chemotherapy drug doxorubicin (DOX) was loaded for achieving a synergistic combination of chemotherapy and photodynamic therapy. The introduction of hydrophilic chains at the 3,5-position through the Knoevenagel reaction enhanced the water solubility and lengthened the conjugated structure of NBDP, resulting in a red shift of the spectrum to the near-infrared (NIR) region. The introduction of iodine atoms at the 2,6-position enhanced the intersystem crossing through the heavy atom effect and promoted singlet oxygen generation (ΦΔ = 71.1%), thereby enhancing the photodynamic therapy. Meanwhile, encapsulated DOX endowed the nanodrug with a chemotherapeutic effect, which compensated for the defects of photodynamic therapy, including the limitation of treatment depth. In vitro and in vivo experiments revealed the actualisation of NIR fluorescent imaging-guided chemo-photodynamic synergistic therapy. Hence, this multifunctional nano-system without extra carriers provides greater insight into the development of drug self-delivery systems with high drug utilization for the multi-modal diagnosis and treatment of cancer.