Supramolecular prodrug-like nanotheranostics with dynamic and activatable nature for synergistic photothermal immunotherapy of metastatic cancer.

Synergistic photothermal immunotherapy has attracted widespread attention due to the mutually reinforcing therapeutic effects on primary and metastatic tumors. However, the lack of clinical approval nanomedicines for spatial, temporal, and dosage control of drug co-administration underscores the challenges facing this field. Here, a photothermal agent (Cy7-TCF) and an immune checkpoint blocker (NLG919) are conjugated via disulfide bond to construct a tumor-specific small molecule prodrug (Cy7-TCF-SS-NLG), which self-assembles into prodrug-like nano-assemblies (PNAs) that are self-delivering and self-formulating. In tumor cells, over-produced GSH cleaves disulfide bonds to release Cy7-TCF-OH, which re-assembles into nanoparticles to enhance photothermal conversion while generate reactive oxygen species (ROSs) upon laser irradiation, and then binds to endogenous albumin to activate near-infrared fluorescence, enabling multimodal imaging-guided phototherapy for primary tumor ablation and subsequent release of tumor-associated antigens (TAAs). These TAAs, in combination with the co-released NLG919, effectively activated effector T cells and suppressed Tregs, thereby boosting antitumor immunity to prevent tumor metastasis. This work provides a simple yet effective strategy that integrates the supramolecular dynamics and reversibility with stimuli-responsive covalent bonding to design a simple small molecule with synergistic multimodal imaging-guided phototherapy and immunotherapy cascades for cancer treatment with high clinical value.

Nanoscale porphyrin assemblies based on charge-transfer strategy with enhanced red-shifted absorption.

Charge-transfer assemblies (CTAs) represent a new class of functional material due to their excellent optical properties, and show great promise in the biomedical field. Porphyrins are widely used photosensitizers, but the short absorption wavelengths may restrict their practical applications. To obtain porphyrin phototherapeutic agents with red-shifted absorption, charge-transfer nanoscale assemblies (TAPP-TCNQ NPs) of 5,10,15,20-tetrakis(4-aminophenyl) porphyrin (TAPP) and 7,7,8,8­tetracyanoquinodimethane (TCNQ) were prepared via optimizing the stoichiometric ratios of donor-acceptor. The as-prepared TAPP-TCNQ NPs exhibit red-shifted absorption to the near-infrared (NIR) region and enhanced absorbance because of the charge-transfer interactions. In especial, TAPP-TCNQ NPs possess the capacity of both photodynamic and photothermal therapy, thus effectively killing the bacteria upon 808 nm laser irradiation. This modular assembly method provides an alternative strategy to enhance the application of the phototherapeutic agents.

Ternary System of Bacogenins with Fulvic Acid and Hydrogenated Soy Lecithin: Preparation, Characterization and, In vivo Studies.

AIMS: The aim of this study was to simultaneously enhance the solubility and stability of bacogenins hydrolyzed bacoside rich extract by a ternary system comprised of hydrogenated soy lecithin and a third auxiliary substance, fulvic acid. METHODS: Both ternary and binary complexes were prepared using the solvent evaporation method were characterized by Fourier transform infrared technique, differential scanning calorimeter and scanning electron microscope. The entrapment efficacy in both binary and ternary system was calculated and the effect on the solubility, dissolution and stability of bacogenins was found out. Furthermore, the prepared complexes were subjected to behavioural pharmacological studies. RESULTS: FTIR, DSC, and SEM studies in totality confirmed the formation of binary and ternary complexes. Enhancement in solubility was observed, and the order of release characteristics was found to be BHFS> BHSL>BHF> BH when the dissolution studies were carried out in 40% aqueous solution of ethanol. A significant improvement in the memory and antioxidant capacity was noticed in both binary, ternary complexes and fulvic acid treatment groups. CONCLUSION: The results revealed that the ternary complex could be a promising drug delivery system to improve the oral bioavailability of the bacogenins.

A Supramolecular Strategy to Engineering a Non-photobleaching and Near-Infrared Absorbing Nano-J-Aggregate for Efficient Photothermal Therapy.

The design of organic photothermal agents (PTAs) for in vivo applications face a demanding set of performance requirements, especially intense NIR-absorptivity and sufficient photobleaching resistance. J-aggregation offers a facile way to tune the optical properties of dyes, thus providing a general design platform for organic PTAs with the desired performance. Herein, we present a supramolecular strategy to build a water-stable, nonphotobleaching, and NIR-absorbing nano-PTA (J-NP) from J-aggregation of halogenated BODIPY dyes (BDP) for efficient in vivo photothermal therapy. Multiple intermolecular halogen-bonding and π-π stacking interactions triggered the formation of BDP J-aggregate, which adsorbed amphiphilic polymer chains on the surface to provide PEGylated sheetlike nano-J-aggregate (J-NS). We serendipitously discovered that the architecture of J-NS was remodeled during a long-time ultrafiltration process, generating a discrete spherical nano-J-aggregate (J-NP) with controlled size. Compared with J-NS, the remodeled J-NP significantly improved cellular uptake efficiency. J-aggregation brought J-NP striking photothermal performance, such as strong NIR-absorptivity, high photothermal conversion efficiency up to 72.0%, and favorable nonphotobleaching ability. PEGylation and shape-remodeling imparted by the polymer coating enabled J-NP to hold biocompatibility and stability in vivo, thereby exhibiting efficient antitumor photothermal activities. This work not only presents a facile J-aggregation strategy for preparing PTAs with high photothermal performance but also establishes a supramolecular platform that enables the appealing optical functions derived from J-aggregation to be applied in vivo.

Glycolipid-Based Oleogels and Organogels: Promising Nanostructured Structuring Agents.

Over the past few decades, the scientific community is actively involved in the development of edible structuring agents suitable for food, cosmetics, agricultural, pharmaceutical, and biotechnology applications. In particular, edible oil structuring using simple amphiphiles would be the best alternative for the currently used trans and saturated fatty acids, which cause deleterious health effects and cardiovascular problems. In this report, we have made an attempt to address the aforementioned consequences, by synthesizing a new class of structuring agents by a judicious combination of δ-gluconolactone and ricinoleic acid, compounds classified as GRAS, using simple steps in good yield. To our delight, the synthesized glycolipids self-assemble in a wide variety of vegetable oils and commercially viable glycerol, ethylene glycol, and polyethylene glycol via various intermolecular interactions to form a gel. The morphology of molecular gels was investigated by optical microscopy and FESEM analysis, which reveal the existence of a tubular architecture with a diameter ranging from 75 to 150 nm. Rheological studies disclosed the viscoelastic nature, thermal processability, and thixotropic behavior of both oleogels and organogels. Altogether, self-assembled oleogel and organogel reported in this paper would potentially be used in food, agricultural, cosmetics, pharmaceutical, and biotechnological applications.

Actin Cytoskeleton-Disrupting and Magnetic Field-Responsive Multivalent Supramolecular Assemblies for Efficient Cancer Therapy.

Actin cytoskeleton disruption is a promising and intriguing anticancer strategy, but their efficiency is frequently compromised by severe side effects of the actin cytoskeleton-disrupting agents. In this study, we constructed the biocompatible actin cytoskeleton-targeting multivalent supramolecular assemblies that specifically target and disrupt the tumor actin cytoskeleton for cancer therapy. The assemblies were composed of ß-cyclodextrin-grafted hyaluronic acid (HACD) and iron oxide magnetic nanoparticles (MNPs) grafted by an actin-binding peptide (ABP) and adamantane (Ada)-modified polylysine. Owing to the multivalent binding between cyclodextrin and Ada, HACD, and peptide-grafted MNPs (MNP-ABP-Ada) could self-assemble to form MNP-ABP-Ada⊂HACD nanofibers in a geomagnetism-dependent manner. Furthermore, the presence of ABP rendered the assemblies to efficiently target the actin cytoskeleton. Interestingly, with the acid of a low-frequency alternating magnetic field (200 Hz), the actin cytoskeleton-targeting nanofibers could induce severe actin disruption, leading to a remarkable cell cycle arrest and drastic cell death of tumor cells both in vitro and in vivo, but showed no obvious toxicity to normal cells. The actin cytoskeleton-targeting/disrupting supramolecular assembly implies an excellent strategy for realizing efficient cancer therapy.

Tumor Microenvironment-Triggered Supramolecular System as an In Situ Nanotheranostic Generator for Cancer Phototherapy.

The efficacy of photosensitizers in cancer phototherapy is often limited by photobleaching, low tumor selectivity, and tumor hypoxia. Assembling photosensitizers into nanostructures can improve photodynamic therapy efficacy and the safety profile of photosensitizers. Herein by employing supramolecular assembly, enhanced theranostic capability of Mn2+ -assisted assembly of a photosensitizer (sinoporphyrin sodium, DVDMS) is demonstrated. A tumor environment-triggered coassembly strategy is further developed to form Mn/DVDMS nanotheranostics (nanoDVD) for cancer phototherapy. MnO2 nanosheets serve as a highly effective DVDMS carrier and in situ oxygen and nanoDVD generator. In MCF-7 cells and xenograft tumors, MnO2 /DVDMS is reduced by glutathione (GSH) and H2 O2 and reassembled into nanoDVD, which can be monitored by activated magnetic resonance/fluorescence/photoacoustic signals. Intriguingly, the decrease of GSH, the production of O2 , and the formation of nanoDVD are shown to be synergistic with phototherapy to improve antitumor efficacy in vitro and in vivo, offering a new avenue for cancer theranostics.

Molecular recognition by gold, silver and copper nanoparticles.

The intrinsic physical properties of the noble metal nanoparticles, which are highly sensitive to the nature of their local molecular environment, make such systems ideal for the detection of molecular recognition events. The current review describes the state of the art concerning molecular recognition of Noble metal nanoparticles. In the first part the preparation of such nanoparticles is discussed along with methods of capping and stabilization. A brief discussion of the three common methods of functionalization: Electrostatic adsorption; Chemisorption; Affinity-based coordination is given. In the second section a discussion of the optical and electrical properties of nanoparticles is given to aid the reader in understanding the use of such properties in molecular recognition. In the main section the various types of capping agents for molecular recognition; nucleic acid coatings, protein coatings and molecules from the family of supramolecular chemistry are described along with their numerous applications. Emphasis for the nucleic acids is on complementary oligonucleotide and aptamer recognition. For the proteins the recognition properties of antibodies form the core of the section. With respect to the supramolecular systems the cyclodextrins, calix[n]arenes, dendrimers, crown ethers and the cucurbitales are treated in depth. Finally a short section deals with the possible toxicity of the nanoparticles, a concern in public health.