Fan Liu

Nanomaterials offer enhanced stability and functionality for photothermal agents; however, their efficacy is often limited by suboptimal cellular internalization and photothermal conversion efficiency. To address these challenges, we designed a multicomponent inorganic-organic hybrid photothermal agent that integrates a virus-mimicking morphology and stimuli-responsive components. Gold nanostars (GNS) were functionalized with a pH-responsive epigallocatechin gallate (EGCG) polyphenol network, followed by in situ growth of CuS, yielding star-shaped GEC nanoassemblies with a rough surface. This biomimetic design leverages (i) the plasmonic photothermal properties of the GNS core, (ii) the acid-triggered disassembly of the EGCG network (mimicking viral protein shells), and (iii) the in situ synthesized CuS layer exhibiting a virus-mimetic rough surface and targeting capability, which enhances near-infrared light absorption and promotes endocytosis by the target cells. The synergistic integration of GNS and CuS significantly enhanced the photothermal conversion efficiency. Under tumor acidic conditions, the EGCG network disintegrated, leading to the shedding of the CuS shell and a reduction in overall size, which facilitated deep tissue penetration. Structural characterization confirmed the hierarchical architecture and pH-responsive size transition. Compared to unmodified GNS, the cellular uptake of GEC by 4T1 cells was approximately 4.5-fold higher, attributable to its virus-like rough surface, acid-responsive disintegration, and targeting ability. This work demonstrates a rational biomimetic strategy for engineering stimuli-responsive inorganic-organic hybrids with optimized photothermal performance through biomimetic component engineering.

Nanocarriers have been extensively utilized to improve the stability of photothermal agents in vivo, enhance delivery efficiency, and reduce drug side effects. However, challenges, such as the low safety of carrier materials, insufficient loading of therapeutic agents, and complex preparation procedures, still persist. In this study, the photothermal agent IR780 was encapsulated in network TA-Fe³⁺ (TF) which was self-assembled by tannic acid (TA) and Fe³⁺ to synthesize an acid-responsive multifunctional nanophotothermal agent TF@IR780 (TR). In the slightly acidic tumor microenvironment (TME), network shell TF is degraded, and the internal photothermal agent IR780 is exposed. On the one hand, the TF network can improve the solubility and stability of photothermal agent IR780 in vivo and significantly increase the uptake efficiency in tumor cells. On the other hand, Fe³⁺ exhibits magnetic resonance imaging (MRI) functionality, which combined with the fluorescence imaging of IR780 endows TR with multimodal imaging capabilities. In addition, TR is easy to release photosensitizers through acid response in the low pH environment of TME, and achieves precise damage to mitochondria through mitochondrial anchoring and light regulation. This overcomes the drawbacks of traditional tumor treatment methods, such as poor specificity, and demonstrates efficient and controllable antitumor activity.

A tumor-targeting fluorescent probe has attracted increasing interest in fluorescent imaging for the noninvasive detection of cancers in recent years. Sulfonamide-containing naphthalimide derivatives (SN-2NI, SD-NI) were synthesized by the incorporation of N-butyl-4-ethyldiamino-1,8-naphthalene imide (NI) into sulfonamide (SN) and sulfadiazine (SD) as the tumor-targeting groups, respectively. These derivatives were further characterized by mass spectrometry (MS), nuclear magnetic resonance spectroscopy (¹H NMR), Fourier transform infrared spectroscopy (FT-IR), ultraviolet–visible spectroscopy (UV), and a fluorescence assay. In vitro properties, including cell cytotoxicity and the cell uptake of tumor cells, were also evaluated. Sulfonamide-containing naphthalimide derivatives possessed low cell cytotoxicity to B16F10 melanoma cells. Moreover, SN-2NI and SD-NI can be taken up highly by B16F10 cells and then achieve good green fluorescent images in B16F10 cells. Therefore, sulfonamide-containing naphthalimide derivatives can be considered to be the potential probes used to target fluorescent imaging in tumors.

Mitochondria-targeting photothermal therapy could significantly enhance the tumor cell killing effect. However, since therapeutic reagents need to overcome a series of physiological obstacles to arrive at mitochondria accurately, precise mitochondria-targeting photothermal therapy still faces great challenges. In this study, we developed a self-delivery nanoplatform that specifically targeted the mitochondria of tumor cells for precise photothermal therapy. Photothermal agent IR780 was encapsulated by amphiphilic apoptotic peptide KLA with mitochondria-targeting ability to form nanomicelle KI by self-assembly through hydrophilic and hydrophobic interactions. Subsequently, negatively charged tumor-targeting polymer HA was coated on the surface of KI through electrostatic interactions, to obtain tumor mitochondria-targeting self-delivery nanoplatform HKI. Through CD44 receptor-mediated recognition, HKI was internalizated by tumor cells and then disassembled in an acidic environment with hyaluronidase in endosomes, resulting in the release of apoptotic peptide KLA and photothermal agent IR780 with mitochondria anchoring capacity, which achieved precise mitochondria guidance and destruction. This tumor mitochondria-targeting self-delivery nanoplatform was able to effectively deliver photothermal agents and apoptotic peptides to tumor cell mitochondria, resulting in precise destruction to mitochondria and enhancing tumor cell inhibition at the subcellular organelle level.

Photothermal therapy (PTT) is an effective cancer treatment method. Due to its easy focusing and tunability of the irradiation light, direct and accurate local treatment can be performed in a noninvasive manner by PTT. This treatment strategy requires the use of photothermal agents to convert light energy into heat energy, thereby achieving local heating and triggering biochemical processes to kill tumor cells. As a key factor in PTT, the photothermal conversion ability of photothermal agents directly determines the efficacy of PTT. In addition, photothermal agents generally have photothermal imaging (PTI) and photoacoustic imaging (PAI) functions, which can not only guide the optimization of irradiation conditions but also achieve the integration of disease diagnosis. If the photothermal agents have function of fluorescence imaging (FLI) or fluorescence enhancement, they can not only further improve the accuracy in disease diagnosis but also accurately determine the tumor location through multimodal imaging for corresponding treatment. In this paper, we summarize recent advances in photothermal agents with FLI or fluorescence enhancement functions for PTT and tumor diagnosis. According to the different recognition sites, the application of specific targeting photothermal agents is introduced. Finally, limitations and challenges of photothermal agents with fluorescence imaging/enhancement in the field of PTT and tumor diagnosis are prospected.

Novel cooperative ZnS–CdSe@Co/N–C core/shell composites were successfully prepared by the chelation of CoCl₂ on the surface of ZnS–CdSe nanoparticles and further modification by N-doped carbon spheres. These composites possessed a heterojunction and cocatalyst properties and can reduce the energy band, promote the activity and selectivity, and enhance the catalyst service life. Therefore these composites may offer a new strategy to regulate the optical absorption and photocatalytic properties of semiconductor materials.

Photothermal therapy directly acting on the nucleus is a potential anti-tumor treatment with higher killing efficiency. However, in practical applications, it is often difficult to achieve precise nuclear photothermal therapy because agents are difficult to accurately anchor to the nucleus. Therefore, it is urgent to develop a nanoheater that can accurately locate the nucleus. Here, we designed an amphiphilic arginine-rich dendritic peptide (RDP) with the sequence CRRK(RRCG(Fmoc))₂, and prepared a nucleus-targeting nanoplatform RDP/I by encapsulating the photothermal agent IR780 in RDP for precise photothermal therapy of the tumor nucleus. The hydrophobic group Fmoc of the dendritic peptide provides strong hydrophobic force to firmly encapsulate IR780, which improves the solubility and stability of IR780. Moreover, the arginine-rich structure facilitates cellular uptake of RDP/I and endows it with the ability to quickly anchor to the nucleus. The nucleus-targeting nanoplatform RDP/I showed efficient nuclear enrichment ability and a significant tumor inhibition effect.

Fluorescent imaging has been expanded, as a non-invasive diagnostic modality for cancers, in recent years. Fluorescent probes in the near-infrared window can provide high sensitivity, resolution, and signal-to-noise ratio, without the use of ionizing radiation. Some fluorescent compounds with low molecular weight, such as rhodamine B (RhB) and indocyanine green (ICG), have been used in fluorescent imaging to improve imaging contrast and sensitivity; however, since these probes are excreted from the body quickly, they possess significant restrictions for imaging. To find a potential solution to this, this work investigated the synthesis and properties of novel macromolecular fluorescent compounds. Herein, water-soluble dextran fluorescent compounds (SD-Dextran-RhB) were prepared by the attachment of RhB and sulfadiazine (SD) derivatives to dextran carrier. These fluorescent compounds were then characterized through IR, ¹H NMR, ¹³C NMR, UV, GPC, and other methods. Assays of their cellular uptake and cell cytotoxicity and fluorescent imaging were also performed. Through this study, it was found that SD-Dextran-RhB is sensitive to acidic conditions and possesses low cell cytotoxicities compared to normal 293 cells and HepG2 and HeLa tumor cells. Moreover, SD-Dextran-RhB demonstrated good fluorescent imaging in HepG2 and HeLa cells. Therefore, SD-Dextran-RhB is suitable to be potentially applied as a probe in the fluorescent imaging of tumors.