J-Aggregation-Driven Supramolecular Assembly of Dye-Conjugated Block Polymers: From Morphological Tailoring to Anticancer Applications

Utilizing the J-stacking of dyes to drive the assembly of amphiphilic polymers can not only construct supramolecular assemblies with novel architectures but also provide a stabilizing solution for dye J-aggregation to promote its biomedical applications. However, tightly entangled hydrophobic segments can disrupt the orderly arrangement of dye molecules, thereby preventing dye stacking-driven supramolecular assembly of block copolymers. Herein, a “molecular glue” strategy is reported that uses the small dye molecule as a molecular glue to restore the J-stacking of the dye moiety immobilized on the polymer, thereby dominating the supramolecular assembly of the polymer matrix. Very interestingly, the yielded nano-assembly exhibits a novel worm-like structure with alternating straight and bent segments. By passing through nanopores, the bent part is disassembled to afford short nanorod NR-J812 mainly composed of crystalline dye J-aggregates. It shows favorable colloidal and optical stability, suitable size, and high photothermal property, and demonstrates high performance in photoacoustic imaging and photothermal treatment of tumors in vivo. This work provides important insights into not only the self-assembly of amphiphilic polymers with novel supramolecular architectures but also the preparation of J-aggregate materials applicable in vivo, which bring great promise to the biomedical fields.     

Nanoengineering Hybrid Supramolecular Multilayered Biomaterials Using Polysaccharides and Self‐Assembling Peptide Amphiphiles

Developing complex supramolecular biomaterials through highly dynamic and reversible noncovalent interactions has attracted great attention from the scientific community aiming key biomedical and biotechnological applications, including tissue engineering, regenerative medicine, or drug delivery. In this study, the authors report the fabrication of hybrid supramolecular multilayered biomaterials, comprising high‐molecular‐weight biopolymers and oppositely charged low‐molecular‐weight peptide amphiphiles (PAs), through combination of self‐assembly and electrostatically driven layer‐by‐layer (LbL) assembly approach. Alginate, an anionic polysaccharide, is used to trigger the self‐assembling capability of positively charged PA and formation of 1D nanofiber networks. The LbL technology is further used to fabricate supramolecular multilayered biomaterials by repeating the alternate deposition of both molecules. The fabrication process is monitored by quartz crystal microbalance, revealing that both materials can be successfully combined to conceive stable supramolecular systems. The morphological properties of the systems are studied by advanced microscopy techniques, revealing the nanostructured dimensions and 1D nanofibrous network of the assembly formed by the two molecules. Enhanced C2C12 cell adhesion, proliferation, and differentiation are observed on nanostructures having PA as outermost layer. Such supramolecular biomaterials demonstrate to be innovative matrices for cell culture and hold great potential to be used in the near future as promising biomimetic supramolecular nanoplatforms for practical applications.     

Carbon‐Based Photothermal Actuators

Actuators that can convert environmental stimuli into mechanical work are widely used in intelligent systems, robots, and micromechanics. To produce robust and sensitive actuators of different scales, efforts are devoted to developing effective actuating schemes and functional materials for actuator design. Carbon‐based nanomaterials have emerged as preferred candidates for different actuating systems because of their low cost, ease of processing, mechanical strength, and excellent physical/chemical properties. Especially, due to their excellent photothermal activity, which includes both optical absorption and thermal conductivities, carbon‐based materials have shown great potential for use in photothermal actuators. Herein, the recent advances in photothermal actuators based on various carbon allotropes, including graphite, carbon nanotubes, amorphous carbon, graphene and its derivatives, are reviewed. Different photothermal actuating schemes, including photothermal effect–induced expansion, desorption, phase change, surface tension gradient creation, and actuation under magnetic levitation, are summarized, and the light‐to‐heat and heat‐to‐work conversion mechanisms are discussed. Carbon‐based photothermal actuators that feature high light‐to‐work conversion efficiency, mechanical robustness, and noncontact manipulation hold great promise for future autonomous systems.     

Increasing Photothermal Efficacy by Simultaneous Intra‐ and Intermolecular Fluorescence Quenching

Recently, using in situ self‐assembly‐induced fluorescence quenching (i.e., intermolecular quenching denoted herein) of a photothermal agent (PTA) to enhance its photothermal efficiency has proven to be a successful photothermal therapy (PTT) strategy. But to the best of current knowledge, using simultaneous intra‐ and intermolecular fluorescence quenching of a PTA to additionally increase its photothermal efficacy has not been reported. Herein, employing a click condensation reaction and a rationally designed PTA Biotin‐Cystamine‐Cys‐Lys(Cypate)‐CBT ( 1 ), a “smart” strategy is developed of intracellular simultaneous intra‐ and intermolecular fluorescence quenching and applied it to largely increase the photothermal efficacy of the agent both in vitro and in vivo. After being internalized by biotin receptor‐overexpressing cancer cells, 1 is reduced by intracellular glutathione to initiate a CBT‐Cys condensation reaction (intramolecular quenching) and self‐assembly (intermolecular quenching) to form the nanoparticles 1‐NPs (simultaneous intra‐ and intermolecular fluorescence quenching). Experimental results indicate that 1‐NPs have higher fluorescence quenching efficiency than the control PTAs [Thiazole‐Lys(Cypate)‐Benzothiazole]₂ ( 1‐Dimer , intramolecular quenching), and nanoparticles of Cystamine‐Cys(Fmoc)‐Lys(Cypate)‐CBT ( 1‐Fmoc‐NPs , intermolecular quenching). It is envisioned that, by replacing the biotin group on 1 with other targeting warheads, the “smart” strategy is ready to increase the photothermal therapeutic efficiency of their corresponding diseases.     

Hierarchical Self‐Organization of Nanomaterials into Two‐Dimensional Arrays Using Functional Polymer Scaffold

Fabrication of two and three‐dimensional nanostructures requires the development of new methodologies for the assembly of molecular/macromolecular objects on substrates in predetermined arrangements. Templated self‐assembly approach is a powerful strategy for the creation of materials from assembly of molecular components or nanoparticles. The present study describes the development of a facile, template directed self‐assembly of (metal/organic) nanomaterials into periodic micro‐ and nanostructures. The positioning and the organization of nanomaterials into spatially well‐defined arrays were achieved using an amphiphilic conjugated polymer‐aided, self‐organization process. Arrays of honeycomb patterns formed from conjugated C₁₂PPPOH film with homogenous distribution of metal/organic nanomaterials. Our approach offers a straightforward and inexpensive method of preparation for hybrid thin films without environmentally controlled chambers or sophisticated instruments as compared to multistep micro‐fabrication techniques.     

NIR-II Responsive Inorganic 2D Nanomaterials for Cancer Photothermal Therapy: Recent Advances and Future Challenges

Non-invasive cancer photothermal therapy (PTT) is a promising replacement for traditional cancer treatments. The second near-infrared region induced PTT (NIR-II PTT, 1000–1500 nm) with less energy dissipation has been developed for deeper-seated tumor treatment in recent years compared with the traditional first near-infrared light (750–1000 nm). In addition, the use of emerging inorganic 2D nanomaterials as photothermal agents (PTAs) further enhanced PTT efficiency due to their intrinsic photothermal properties. NIR-II light stimulated inorganic 2D nanomaterials for PTT is becoming a hot topic in both academic and clinical fields. This review summarizes the categories, structures, and photothermal conversion properties of inorganic 2D nanomaterials for the first time. The recent synergistic strategies of NIR-II responsive PTT combined with other treatment approaches including chemotherapy, chemodynamic therapy, photodynamic therapy, radiotherapy are summarized. The future challenges and perspectives on these 2D nanomaterials for NIR-II responsive PTT systems construction are further discussed.     

Heptamethine Cyanine-Based Nanotheranostics with Catalase-Like Activity for Synergistic Phototherapy of Cancer

Single-molecule photosensitizers (PSs) for synergistic phototherapy are desirable but highly challenging, due to the competitive relationship between photothermal (PTT) and photodynamic therapy (PDT). Herein, a supramolecular strategy is developed that can tune the stacking pattern of PS molecules in their aggregates to optimize the PTT/PDT efficiency. Specifically, near-infrared (NIR) heptamethine cyanines (Cy7) are synthesized using tricyanofuran (TCF) as the acceptor and benzothiazole (BTH)/indole (IND) as the donor, where BTH is a less hydrogen-bonded tecton relative to IND. Both IND-Cy7-TCF and BTH-Cy7-TCF have similar photophysical properties at the molecular level, but BTH-Cy7-TCF in aggregated state exhibits higher singlet oxygen quantum yield (1.3% vs 0.2%) and competitive photothermal conversion efficiency (56.4% vs 62.3%) compared to IND-Cy7-TCF, due to the fine-tuning of hydrogen bonding and intermolecular π–π interactions to form loose molecular stacks. Interestingly, the unique molecular stacking structure provides a binding site and catalytic center for H₂O₂ that exhibits catalase-like activity, which can further ameliorate the efficiency of PDT and enhance the synergistic effect of PDT/PTT phototherapy in vitro and in vivo. This study can provide a simple but effective supramolecular strategy to design small molecule PSs with desirable aggregated structure for synergistic dual-mode phototherapy.     

Facile Nondestructive Assembly of Tyrosine‐Rich Peptide Nanofibers as a Biological Glue for Multicomponent‐Based Nanoelectrode Applications

Achieving the nondestructive assembly of carbon nanoelectrodes with multiple components in a scalable manner enables effective electrical interfaces among nanomaterials. Here, a facile nondestructive multiscale assembly of multicomponent nanomaterials using self‐assembled tyrosine‐rich peptide nanofibers (TPFs) as a biological glue is reported. The versatile functionalities of the rationally devised tyrosine‐rich short peptide allow for (1) self‐assembly of the peptide into nanofibers using noncovalent interactions, followed by (2) immobilization of spatially distributed metal nanoparticles on the nanofiber surface, and (3) subsequent assembly with graphitic nanomaterials into a percolated network‐structure. This percolated network‐structure of silver nanoparticle (AgNP)‐decorated peptide nanofibers with imbedded single‐walled carbon nanotubes (SWNTs) proves to be a versatile nanoelectrode platform with excellent processability. The SWNT–TPF–AgNP assembly, when utilized as a flexible and transparent multicomponent electronic film, was quite effective for enhancing direct electron transfer (DET) as verified for a third‐generation glucose sensor composed of this film. The simple solution process used to produce the functional nanomaterials could provide a new platform for scalable manufacturing of novel nanoelectrode materials forming effective electrical contacts with molecules from diverse biological systems.     

Biocompatible D–A Semiconducting Polymer Nanoparticle with Light‐Harvesting Unit for Highly Effective Photoacoustic Imaging Guided Photothermal Therapy

The development of nanotheranostic agents that integrate diagnosis and therapy for effective personalized precision medicine has obtained tremendous attention in the past few decades. In this report, biocompatible electron donor–acceptor conjugated semiconducting polymer nanoparticles (PPor‐PEG NPs) with light‐harvesting unit is prepared and developed for highly effective photoacoustic imaging guided photothermal therapy. To the best of our knowledge, it is the first time that the concept of light‐harvesting unit is exploited for enhancing the photoacoustic signal and photothermal energy conversion in polymer‐based theranostic agent. Combined with additional merits including donor–acceptor pair to favor electron transfer and fluorescence quenching effect after NP formation, the photothermal conversion efficiency of the PPor‐PEG NPs is determined to be 62.3%, which is the highest value among reported polymer NPs. Moreover, the as‐prepared PPor‐PEG NP not only exhibits a remarkable cell‐killing ability but also achieves 100% tumor elimination, demonstrating its excellent photothermal therapeutic efficacy. Finally, the as‐prepared water‐dispersible PPor‐PEG NPs show good biocompatibility and biosafety, making them a promising candidate for future clinical applications in cancer theranostics.     

Significant Enhancement of Photothermal and Photoacoustic Efficiencies for Semiconducting Polymer Nanoparticles through Simply Molecular Engineering

Semiconducting polymer nanoparticles (SP NPs) are employed as efficient nanoagents for “all‐in‐one” theranostic nanoplatforms with dual photoacoustic imaging (PAI) and photothermal therapy (PTT) functions based on their photothermal conversion effect. However, the mechanisms of tuning the PTT efficiency are still elusive, though several SP NPs with high photothermal efficiency are reported. Herein, two donor–acceptor (D–A) SP NPs PTIGSVS and PIIGSVS with the same donor unit but different acceptor units are designed and synthesized. Through tuning the acceptor unit, PTIGSVS shows more planar backbone structure, stronger D–A strength, redshifted absorption, enhanced extinction efficient, weakened emission properties, and more efficient nonradiative decay in comparison to the polymeric analogue PIIGSVS . Thus, PTIGSVS NPs present much higher photothermal conversion efficiencies (74%) than PIIGSVS NPs (11%), resulting in significantly enhanced in vitro and in vivo PAI and PTT performance. This contribution demonstrates that PTIGSVS NPs are superior PA/PTT agents for effective cancer theranostic and shed light on understanding the relationship between molecular structures and photothermal effect of CPs.     

Spiky Fe3O4@Au Supraparticles for Multimodal In Vivo Imaging

Nanomaterials with high biocompatibility and efficient photothermal conversion have drawn tremendous attention for tumor diagnosis and treatment. In this study, spiky Fe₃O₄@Au supraparticles (SPs) are used as phototherapy and multimodal imaging agents. The SPs show excellent photothermal and photodynamic therapeutic effects, with a photothermal conversion efficiency of 31%, and allow tumor‐targeted imaging, including computed tomographic, photoacoustic, and magnetic resonance imaging. The SPs show excellent biocompatibility both in vitro and in vivo. Furthermore, because of their remarkable absorption at near‐infrared region, the SPs obliterate a tumor under 808 nm irradiation. With their capacity for highly integrated multimodal imaging and multiple therapeutic functions, SPs are a promising agent for application to clinical practice.     

Modular Deformable Steam Electricity Cogeneration System with Photothermal,Water, and Electrochemical Tunable Multilayers

Capturing solar energy for thermal conversion in a highly efficient manner for steam‐electricity cogeneration is particularly opportune in the context of optimal solar energy utilization for concurrent water‐energy harvesting. Herein, an integrative photothermal evaporator/thermogalvanic cell with the desired optical, heat, water, and electrochemical management for synergistic steam‐electricity production is reported. Versatile layer by‐layer assembly is employed to integrate a hydrogel/metal‐oxide/polymer into a multilayer film with individually addressable thickness, composition, and structure. As such, the ultimate integrative multilayer film cell demonstrates a unified high surface area and conductive electrodes, broadband absorption, rapid water suction‐ion exchange, and thermal insulation properties. Thus, the designed cell immensely suppresses heat losses, achieving a high solar thermal conversion efficiency of 91.4% and maximum power outputs of ≈1.6 mW m^?2. Additionally, the self‐floating, deformable, modular integral device presents appealing attributes such as salt‐rejection for viable seawater desalination, high mechanical stability, and resilience to demanding operating conditions, and configurable on‐demand/point‐of‐use tandem structure to maximize clean water and power generation value per area. This integrated strategy may provide prospective opportunities to reduce dependence on fossil fuels and freshwater inputs and solutions for renewable and decentralized clean water and electricity.     

Controlling Spatiotemporal Mechanics of Supramolecular Hydrogel Networks with Highly Branched Cucurbit[8]uril Polyrotaxanes

Attempts to rationally tune the macroscopic mechanical performance of supramolecular hydrogel networks through noncovalent molecular interactions have led to a wide variety of supramolecular materials with desirable functions. While the viscoelastic properties are dominated by temporal hierarchy (crosslinking kinetics), direct mechanistic studies on spatiotemporal control of supramolecular hydrogel networks, based on host–guest chemistry, have not yet been established. Here, supramolecular hydrogel networks assembled from highly branched cucurbit[8]uril‐threaded polyrotaxanes (HBP‐CB[8]) and naphthyl‐functionalized hydroxyethyl cellulose (HECNp) are reported, exploiting the CB[8] host–guest complexation. Mechanically locking CB[8] host molecules onto a highly branched hydrophilic polymer backbone, through selective binary complexation with viologen derivatives, dramatically increases the solubility of CB[8]. Additionally, the branched architecture enables tuning of material dynamics of the supramolecular hydrogel networks via both topological (spatial hierarchy) and kinetic (temporal hierarchy) control. Relationship between macroscopic properties (time‐ and temperature‐dependent rheological properties, thermal stability, and reversibility), spatiotemporal hierarchy, and chain dynamics of the highly branched polyrotaxane hydrogel networks is investigated in detail. Such kind of tuning of material mechanics through spatiotemporal hierarchy improves our understanding of the challenging relationship between design of supramolecular polymeric materials and their complex viscoelasticity, and also highlights a facile strategy to engineer dynamic supramolecular materials.     

Multifunctional Carbon–Silica Nanocapsules with Gold Core for Synergistic Photothermal and Chemo‐Cancer Therapy under the Guidance of Bimodal Imaging

Carbon‐based nanomaterials have been developed for photothermal cancer therapy, but it is still a great challenge to fabricate their multifunctional counterparts with facile methods, good biocompatibility and dispersity, and high efficiency for cancer theranostics. In this work, an alternative multifunctional nanoplatform is developed based on carbon–silica nanocapsules with gold nanoparticle in the cavity (Au@CSN) for cancer theranostics. The encapsulated chemodrug doxorubicin can be released from the Au@CSN with mesoporous and hollow structure in a near‐infrared light and pH stimuli‐responsive manner, facilitating spatiotemporal therapy to decrease off‐target toxicity. The nanocapsules with efficient photothermal conversion and excellent biocompatibility achieve a synergistic effect of photothermal and chemotherapy. Furthermore, the nanocapsules can act as a multimodal imaging agent of computed tomography and photoacoustic tomography imaging for guiding the therapy. This new design platform can provide a promising strategy for precise cancer theranostics.     

Biocompatible Cup‐Shaped Nanocrystal with Ultrahigh Photothermal Efficiency as Tumor Therapeutic Agent

As an emerging treatment for cancer, phototherapy has received much clinical attention. Here, a multifunctional Au nanocup (Au NC) for the targeted computed tomographic and photoacoustic imaging of cancerous tumors and phototherapy is reported. The Au NC has an intrinsic photothermal conversion efficiency of 38.5% and offers a tumor‐specific targeted computed tomographic and photoacoustic imaging system. Furthermore, when treated with nontoxic Au NC‐Ce6, cancer cells and tumors are obliterated with low doses of irradiation and safe power levels, with both photothermal and photodynamic therapeutic effects, in vitro and vivo. These data provide a solid foundation for the clinical application of Au NC.     

Molecular Engineering of “Click”‐Phospholes Towards Self‐Assembled Luminescent Soft Materials

Inspired by the self‐assembled bilayer structures of natural amphiphilic phospholipids, a new class of highly luminescent “click”‐phospholes with exocyclic alkynyl group at the phosphorus center is reported. These molecules can be easily functionalized with a self‐assembly group to generate neutral “phosphole‐lipids”. This novel approach retains the versatile reactivity of the phosphorus center, allowing further engineering of the photophysical and self‐assembly properties of the materials at a molecular level. The results of this study highlight the importance of being able to balance weak intermolecular interactions for controlling the self‐assembly properties of soft materials. Only molecules with the appropriate set of intermolecular arrangement/interactions show both organogel and liquid crystal mesophases with well‐ordered microstructures. Moreover, an efficient energy transfer of the luminescent materials is demonstrated and applied in the detection of organic solvent vapors.     

Ultra‐Small Iron Oxide Doped Polypyrrole Nanoparticles for In Vivo Multimodal Imaging Guided Photothermal Therapy

Recently, near‐infrared (NIR) absorbing conjugated polymeric nanoparticles have received significant attention in photothermal therapy of cancer. Herein, polypyrrole (PPy), a NIR‐absorbing conjugate polymer, is used to coat ultra‐small iron oxide nanoparticles (IONPs), obtaining multifunctional IONP@PPy nanocomposite which is further modified by the biocompatible polyethylene glycol (PEG) through a layer‐by‐layer method to acquire high stability in physiological solutions. Utilizing the optical and magnetic properties of the yielded IONP@PPy‐PEG nanoparticles, in vivo magnetic resonance (MR) and photoacoustic imaging of tumor‐bearing mice are conducted, revealing strong tumor uptake of those nanoparticles after intravenous injection. In vivo photothermal therapy is then designed and carried out, achieving excellent tumor ablation therapeutic effect in mice experiments. These results promise the use of multifunctional NIR‐absorbing organic‐inorganic hybrid nanomaterials, such as IONP@PPy‐PEG presented here, for potential applications in cancer theranostics.     

Cisplatin‐Prodrug‐Constructed Liposomes as a Versatile Theranostic Nanoplatform for Bimodal Imaging Guided Combination Cancer Therapy

Up to date, a large variety of liposomal nanodrugs have been explored for cancer nanomedicine, showing encouraging results in both preclinical animal experiments and clinical treatment of cancer patients. Herein, a phospholipid conjugated with a cisplatin prodrug is used as the major structure component of liposomes together with other commercial lipids via self‐assembling. By doping with 1,1′‐dioctadecyl‐3,3,3′,3′‐tetramethylindotricarbocyanine iodide (DiR), a lipophilic dye with strong near infrared (NIR) absorbance and fluorescence, the obtained DiR‐Pt(IV)‐liposome is found to be an effective probe for in vivo NIR fluorescence and photoacoustic bimodal imaging. Attributing to its intrinsically doped cis‐Pt(IV) prodrug, efficient photothermal conversion ability, and excellent tumor homing ability, DiR‐Pt(IV)‐liposome confers greatly enhanced therapeutic outcomes in the combined photothermal‐chemotherapy. Moreover, Pt(IV)‐liposome is also demonstrated to be an efficient carrier for both small hydrophilic molecules and proteins, which are encapsulated inside the water‐cavity of liposomes, further demonstrating the versatile functions of this nanoplatform. This study develops a unique type of liposomal nanomedicine with a prodrug conjugated phospholipid as the major structure component. Such Pt(IV)‐liposome is featured with advantages including precisely defined/easily tunable drug compositions, stealth‐like pharmacokinetics, efficient tumor passive uptake, and the capabilities to simultaneously load with various types of imaging or therapeutic agents.     

Organic Small Molecule Based Photothermal Agents with Molecular Rotors for Malignant Breast Cancer Therapy

Organic photothermal nanoagents are promising candidates for treating primary tumors and inhibiting metastasis. However, they often exhibit poor photostability, low absorptivity, or limited photothermal conversion efficiency (PCE). Herein, a facile molecular engineering approach to produce efficient organic photothermal molecules is demonstrated. By integrating donor–acceptor structure and molecular motors, a small molecule ( TA1 ) is synthesized with large absorptivity (22.4 L g^?1 cm^?1), negligible reactive oxygen species generation, high PCE (84.8%), excellent photothermal stability, and good biocompatibility. Furthermore, microfluidics is used to thoroughly study the relationship between the size and process conditions, yielding small uniform nanoparticles (NPs) with a diameter of 44 nm. Importantly, TA1 NPs under near‐infrared laser irradiation significantly suppressed primary breast tumor growth and metastasis, both in vitro and in vivo. This study shows that small organic molecule nanoparticles are promising candidates for future cancer nanomedicine.     

Halogen Bonding versus Hydrogen Bonding in Driving Self‐Assembly and Performance of Light‐Responsive Supramolecular Polymers

Halogen bonding is arguably the least exploited among the many non‐covalent interactions used in dictating molecular self‐assembly. However, its directionality renders it unique compared to ubiquitous hydrogen bonding. Here, the role of this directionality in controlling the performance of light‐responsive supramolecular polymers is highlighted. In particular, it is shown that light‐induced surface patterning, a unique phenomenon occurring in azobenzene‐containing polymers, is more efficient in halogen‐bonded polymer–azobenzene complexes than in the analogous hydrogen‐bonded complexes. A systematic study is performed on a series of azo dyes containing different halogen or hydrogen bonding donor moieties, complexed to poly(4‐vinylpyridine) backbone. Through single‐atom substitution of the bond‐donor, control of both the strength and the nature of the noncovalent interaction between the azobenzene units and the polymer backbone is achieved. Importantly, such substitution does not significantly alter the electronic properties of the azobenzene units, hence providing us with unique tools in studying the structure–performance relationships in the light‐induced surface deformation process. The results represent the first demonstration of light‐responsive halogen‐bonded polymer systems and also highlight the remarkable potential of halogen bonding in fundamental studies of photoresponsive azobenzene‐containing polymers.