Hydrophobicity is established as a key regulator of organic phototheranostic nanoparticle stability and reveals opposing effects of salt and serum

A facile strategy for manipulating noncovalent conformational locks to construct highly efficient organic phototheranostic agents

In this work, we designed and synthesised a new cyclometallated iridium(iii) nitrone complex [Ir(bpz)2(bpy-nitrone)](PF6) (1) (Hbpz = benzo[a]phenazine; bpy-nitrone = 4-((methyl(oxido)imino)methyl)-4′...

This Protocol describes the synthesis of NIR-II aggregation-induced emission agents with photothermal properties, which are coated with membranes of preactivated macrophages to target granulomas in My...

This study introduces a synergistic S-O conformation locking and alkoxy chain engineering strategy to enhance S-D-A-D-S molecular planarity. The engineered IR-BTOG achieves concurrent NIR-IIa absorption and NIR-IIb emission, demonstrating exceptional photothermal efficiency and fluorescence quantum yield. GPC3-targeted BTOGP-GPC3 nanoparticles enable precise diagnosis and treatment of deep-seated hepatic tumors, advancing NIR-II biomedical applications. Abstract NIR-II phototheranostics offers a promising strategy for precisely managing deep-seated and refractory tumors. However, the overall optimization of molecular functional properties remains a challenge, and due to the lack of a comprehensive design strategy, there have been limitations in achieving long-wavelength phototherapy, high-fluorescence quantum yield, and photothermal/photodynamic conversion efficiency. This study initially proposes an innovative strategy that involves S···O confirmation locks (SoCLs), synergistic alkoxy chain engineering, and the regulatory influence of the SoCLs on NIR-II S-D-A-D-S-type (shield-donor-acceptor-donor-shield) molecular planarity and successfully optimizes the molecular structure. The resulting IR-BTOG molecules exhibit extended coverage across the NIR-IIa (λex: 1000–1300 nm) and NIR-IIb (λem: 1500–1700 nm) regions, achieving high fluorescence quantum yields and significantly improved photothermal performance. Building on this molecular design, BTOGP-GPC3 nanoparticles (NPs) are further developed by conjugating the hepatocellular carcinoma (HCC)-specific targeting molecule Glypican-3 peptide (GPC3). This conjugation enables precise recognition and diagnosis of HCC. The excellent phototheranostic performance of BTOGP-GPC3 NPs confirms that the SoCLs synergistic alkoxy chain modification strategy markedly enhances the diagnostic performance of the molecule in deep-seated tumors, offering novel opportunities for applying precision phototheranostics in HCC. Moreover, it provides a significant structural design foundation for the future advancement of NIR-II phototheranostic formulations.

A “3+2” cooperation pattern of amphipathicity PTA (named TDTMSB) with aggregation-induced emission (AIE) features is designed and synthesized to perform near-infrared I/II fluorescence imaging, photoacoustic imaging, photothermal imaging, and Type I/II photodynamic therapy (PDT)-photothermal therapy (PTT) synergistic phototherapy for malignant tumors. Abstract Phototheranostic agents (PTA) control the process of phototheranostics for cancer. However, the existing PTA still cannot meet the needs of practical biomedical applications. Hence the development of new PTA will be imperative. In this contribution, a “3+2” cooperation pattern of amphipathicity PTA (named TDTMSB) with aggregation-induced emission (AIE) features is designed and synthesized to perform near-infrared I/II fluorescence imaging, photoacoustic imaging, photothermal imaging, and Type I/II photodynamic therapy (PDT)-photothermal therapy (PTT) synergistic phototherapy for malignant tumors. Briefly, the target products (TMSB, TTMSB and TDTMSB) are successfully prepared by the reaction of 2-methyl-1-(3-sulfonatepropyl)-benzothiazolium (MSB) and triphenylamine derivatives. They have high rotor twisted structure, doner-acceptor (D-A) conformation and unique AIE performances. Compared to TMSB and TTMSB, the TDTMSB exhibits a long near infrared emission that extends into the NIR II region, large Stokes shift (300 nm) and small energy gap. Simultaneously, it shows high ROSs generation capacity ( 1 O 2 , OH, and O 2 − ), photothermal conversion efficiency (up to 40.5%), and specific recognition of lysosomes in tumor cells. Furthermore, TDTMSB not only exhibits excellent multimodal imaging capabilities, but also carry out Type I/II PDT-PTT synergistic enhancement effect for malignant tumor. Therefore, TDTMSB is expected to be a promising PTA for multimodal image-guided phototherapy of tumors.

Mesoporous gold nanospheres confined platinum nanoclusters (MGNSs@Pt) is developed as robust hydroxyl radical and oxygen nanogenerators for multimodal therapies. Their NIR-II LSPR property also allowed MGSNs to be ideal phototheranostic agents. The chemodynamic and photothermal therapy efficiently induced the tumor cell apoptosis, enabling the MGNSs@Pt nanocatalysts to exhibit an excellent tumor inhibition rate in 4T1-tumor-bearing mice. Abstract While massive studies are focused on platinum (Pt)-based nanozyme for antitumor therapies, their therapeutic efficiency is deficient due to the weak catalytic activity in the highly complex tumor microenvironment. Herein, mesoporous gold nanospheres confined platinum nanoclusters (MGNSs@Pt) as robust hydroxyl radical and oxygen nanogenerators are achieved for multimodal therapies. Benefiting from the confinement effect of the mesopores in the MGNSs, the Pt nanoclusters (Pt NCs) demonstrate enhanced stability and catalytic activity, with a catalytic constant (K cat ) of 1.42 × 10 6  s −1 , which is 2 and 5 orders magnitude higher than K cat values of Pt-decorated non-porous gold nanoparticles and pure Pt NCs respectively. Density functional theory (DFT) calculations reveal the proper interaction of intermediates contributes to the ultra-high catalytic activity of MGNSs@Pt. Meanwhile, owing to the local surface plasmon resonance (LSPR) effect in the second near-infrared (NIR-II) bio-window of MGNSs, the nanozymes exhibited high photothermal conversion efficiency up to 43.4%, which enhanced the nanocatalytic damage on cancer cells. This process can induce robust oxidative stress and oxygenation within the tumor, thereby activating the apoptosis pathway for tumor eradication by mitochondrial dysfunction, cell membrane disruption, HIF-1α downregulation as well as caspase 3 activation, which pave the way for multimodal and effective cancer treatment.

The hydrogen-bonding interactions of the hydroxy end group can induce a more intensive π–π electron coupling than the chlorination-mediated intermolecular forces. π–π stacking will lower fluorescence quantum yield but significantly benefit the PDT efficiency. Therefore, by this end-group strategy, the phototheranostic properties of the photosensitizers are finely tuned, and a more effective NIR-II fluorescence-guided PDT is accomplished. Abstract Deep NIR organic phototheranostic molecules generally have large π-conjugation structures and show highly hydrophobic properties, thus, forming strong π–π stacking in the aqueous medium, which will affect the phototheranostic performance. Herein, an end-group strategy is developed to lift the performance of NIR-II emitting photosensitizers. Extensive characterizations reveal that the hydrogen-bonding interactions of the hydroxyl end group can induce a more intense π–π electronic coupling than the chlorination-mediated intermolecular forces. The results disclose that π–π stacking will lower fluorescence quantum yield but significantly benefit the photodynamic therapy (PDT) efficiency. Accordingly, an asymmetrically substituted derivative (BTIC- δ OH-2Cl) is developed, which shows balanced phototheranostic properties with excellent PDT efficiency (14.6 folds of ICG) and high NIR-II fluorescence yield (2.27%). It proves the validity of the end-group strategy on controlling the π–π interactions and rational tuning the performance of NIR-II organic phototheranostic agents.