Photothermal Tumor Research Articles

Highly Stable Near-Infrared II Luminescent Diradicaloids for Cancer Phototheranostics.

Near-infrared II (NIR-II) phototheranostic agents have become prominent agents for the early diagnosis and precise treatment of cancer. Organic open-shell diradicaloids with distinct structure and narrow band gap are promising candidates for phototherapeutic agents due to their strong spin-coupling effect and NIR light-harvesting capacity. However, achieving stable and efficient NIR-II luminescent diradicaloids is crucial yet rather challenging considering their high chemical reactivity and self-absorption. Herein, two highly stable NIR-II luminescent diradicaloids, 2PhNVDPP and PhNVDPP, were successfully fabricated by employing an acceptor planarization/π-conjugation extension and donor rotation strategy. After encapsulation into water-dispersible nanoparticles (NPs), 2PhNVDPP NPs exhibit NIR-II luminescence, high PCE of 53%, and improved photo/heat stability. In vivo experiments with 2PhNVDPP NPs demonstrated the clear visualization of blood vessels and tumors, as well as the successful NIR-II imaging-guided photothermal ablation of tumors. This study not only develops a pioneering stable diradicaloid phototherapeutic agent with NIR-II luminescence but also provides a unique perspective for the effectiveness of multimodal anticancer therapy.

Spatiotemporal Proximity-Enhanced Biocatalytic Cascades Within Metal-Organic Frameworks for Wearable and Theranostic Applications.

Enzymatic catalysis, particularly multi-enzyme cascade catalytic, is often limited by the spatial and temporal separation of enzymes and their signal substrates. Herein, a facile method for producing a spatiotemporal proximity-enhanced biocatalytic cascade system is introduced by encasing enzymes within metal-organic frameworks (MOFs) that are modulated with sulfonic acid-functionalized signal substrates. The modulated behavior relies on the sulfonic acid groups coordinated with Zn2+. As a proof of concept, by utilizing 2,2'-Azinobis (3-ethylbenzothiazoline-6-sulfonic acid ammonium salt) (ABTS), a widely-used signal substrate for horseradish peroxidase, two-enzyme/substrate, and three-enzyme/substrate MOFs, which demonstrated a 7.4- and 10.2-fold increase in biocatalytic efficiency over free systems are successfully synthesized. Incorporating the synthesized MOFs into homemade wearable patches and in vivo settings, noninvasive sweat glucose colorimetric detection and photoacoustic imaging-guided photothermal tumor therapy are enabled, respectively. This advancement stems from the newly established coordinative bonds between Zn2+ centers and substrates' sulfonic acid groups, which negates the need for additional signal substrates, thereby not only enhancing but also streamlining bioapplication processes.

Donor Substitution Engineering of Hemicyanine Nanoparticles to Reprogram the Tumor Microenvironment and Enhance Fn14‐Targeted BiTE for Glioblastoma Photoimmunotherapy

AbstractGlioblastoma (GBM) is a highly malignant intracranial tumor with limited treatment options. Bispecific T‐cell engagers (BiTEs) are being explored for GBM treatment, but their success is hindered by inadequate T cell infiltration and activation due to the acidic and immunosuppressive microenvironment. Photothermal immunotherapy lyses tumors and activates immune responses, complementing BiTEs. This study innovatively employs a donor engineering strategy to develop hemicyanine dyes (Hcys) that emit from near‐infrared (NIR) I to NIR II. The Hcy with excellent properties is encapsulated in an amphiphilic micelle, forming a nano assembly with lactate oxidase (PLH1100). PLH1100 exhibits spectral absorption at 980 nm, a photothermal conversion efficiency of 58.7%, and capability for NIR‐II tumor imaging. Besides photothermal tumor ablation, PLH1100 regulates lactic acid metabolism and activates immunogenic cell death, improving the tumor microenvironment and promoting T cell infiltration and activation. Further studies demonstrate PLH1100 effectively kills human and murine GBM cells, inhibits orthotopic U87 tumor growth in BALB/c‐nu mice, and enhances the efficacy of Fn14‐targeted BiTE in orthotopic GL261 tumors in C57BL/6 mice, achieving a synergistic “1+1>2” therapeutic effect. Collectively, this work opens a new pathway for using Hcy‐based molecules combined with BiTE drugs for GBM therapy, with significant clinical potential.

Manganese-doped liquid metal nanoplatforms for cellular uptake and glutathione depletion-enhanced photothermal and chemodynamic combination tumor therapy

Chemodynamic therapy (CDT) involves the catalysis of in situ overexpressed hydrogen peroxide (H2O2) into highly toxic reactive oxygen species (ROS) to treat tumors. However, the efficacy of CDT is greatly hampered by limited cellular internalization efficiency, ROS scavenging by glutathione (GSH), and slow reaction rate. To overcome the current limitations of CDT, a manganese-doped and polyethylene glycol (PEG)-modified liquid metal (LM)-silica nanoplatform (labeled as Mn-LMOP) with varying stiffness is constructed to achieve synergistic photothermal therapy (PTT) and CDT, which can further induce immunogenic cell death (ICD) in tumors to enhance the anti-tumour effects. Significantly, benefiting from the increased stiffness, the Mn-LMOP nanoparticles (NPs) can enhance cellular uptake and lysosomal escape, and gradually accumulate in tumor sites. Moreover, manganese-doped NPs exhibite good photothermal effects and can rapidly reacte with intratumoral GSH to produce Mn2+, inhibiting GSH-mediated ROS clearance and promoting the efficiency of CDT. This combined treatment strategy can activate the immune response of the tumors, which holds the promise of photothermal/chemodynamic/immune multimodal therapeutic effects. This LM-based nanosystem will provide a paradigm for enhanced CDT/PTT combination anti-tumour efficacy. Statement of significanceChemodynamic therapy (CDT) is a promising drug-free treatment approach characterized by its low invasiveness and minimal side effect. However, CDT encounters challenges such as high levels of glutathione (GSH), low Fenton-like reaction rate, and inefficient cellular uptake in tumor tissues. Here, a manganese-doped liquid metal (LM) nanomaterial was designed to achieve synergistic photothermal therapy (PTT) and CDT. This innovative strategy enhanced cellular uptake by adjusting the mechanical property of nanoparticles (NPs) and facilitated the consumption of GSH, while simultaneously accelerating the Fenton-like reaction rate with the assistance of PTT-mediated hyperthermia. This combined CDT/PTT strategy also activated the immune response within the tumor, demonstrating significant therapeutic potential.

Molecular Engineering of Xanthene Dyes with 3D Multimodal-Imaging Ability to Guide Photothermal Therapy.

Phototheranostics integrates light-based diagnostic techniques with therapeutic interventions, offering a non-invasive, precise, and swift approach for both disease detection and treatment. The efficacy of this approach hinges on the multimodal imaging potential and photothermal conversion efficiency (PCE) of phototheranostic agents (PTAs). Despite the promise, crafting multifunctional phototheranostic organic small molecules brims with challenges. In this research, four innovative xanthene-derived PTAs are synthesized by fine-tuning the donor-π-acceptor (D-π-A) system to strike a balance between radiative and nonradiative decay. The inherent robust photostability and intense fluorescence of the traditional xanthene core are preserved, meanwhile the addition of highly electron-withdrawing groups boosts the non-radiative decay rate to enhance PCE and photoacoustic imaging capabilities. Remarkably, one of the PTAs, DMBA, demonstrates an exceptional absolute fluorescence quantum yield of 2.46% in PBS, and when encapsulated into nanoparticles, it achieves a high PCE of 79.5%. Consequently, DMBA nanoparticles (DMBA-NPs) are effectively employed in fluorescence, 3D photoacoustic, and photothermal imaging-guiding tumor photothermal therapy. This represents the first instance of a multimodal phototheranostic xanthene agent achieving synergistic fluorescence and photoacoustic imaging for diagnostic purposes. Furthermore, this work paves the way for leveraging xanthene fluorophores as versatile tools in the development of multifunctional reagents.

MMP-2 Responsive Gold Nanorods Loaded with HSP-70 siRNA for Enhanced Photothermal Tumor Therapy.

Gold nanorods (Au NRs) are a valuable photothermal nanomaterial for tumor therapy. However, when treated with Au NRs for photothermal therapy, the expression of heat shock proteins in tumors will increase, which will induce heat resistance in tumor cells and reduce the photothermal therapeutic effect of Au NRs. By RNA interference, the expression of heat shock proteins would be effectively inhibited to improve the efficasy of tumor photothermal therapy. However, deep and noninvasive tissue penetration remains a great obstacle to applying siRNA successfully. Thus, the nanoplatform AGC/HSP-70 siRNA was designed for enhanced photothermal tumor therapy by RNA interference. In the AGC/HSP-70 siRNA complex, the Au-S bond modified the matrix metalloproteinase-2 (MMP-2)-sensitive peptide GPLGLAG on the surface of gold nanorods. Moreover, the natural basic polysaccharide (chitosan) was reacted with the peptide by an amide bond for delivering heat shock protein 70 silencing siRNA (HSP-70 siRNA). Modifying the MMP-2-sensitive linker could cause more Au NRs to accumulate in tumors to exert a photothermal effect and promote the penetration of HSP-70 siRNA and chitosan complexes into deep tumor tissues. In vitro experiments indicated that the enzymolysis of the MMP-2-sensitive linker for AGC/HSP-70 siRNA could promote the cellular uptake and perinuclear distribution of HSP-70 siRNA in tumor cells, which may be due to the smaller size and positive electricity of the complexes. All of these results ensured the efficient gene silencing effect of HSP-70 siRNA to enhance the photothermal therapeutic effect of Au NRs in tumor tissues, as demonstrated by the gene silencing and cellular apoptotic experiments. In vivo experiments further proved that the AGC/HSP-70 siRNA nanoplatform efficiently improved the photothermal effect of Au NRs. In summary, this work proved that AGC/HSP-70 siRNA is a promising drug delivery strategy for enhancing the photothermal therapy of tumors by regulating the photothermal sensitivity of deep tumor cells as well as retaining more Au NRs in tumor tissues, and also provides a novel strategy for tumor photothermal therapy.

Stable Alkyne‐Bridged Conjugated Polymer Nanoparticles With a High NIR‐II Photothermal Conversion Efficiency of 71% for Effective Photothermal Tumor Therapy

AbstractOrganic photothermal materials (PTMs) in the near‐infrared (NIR) range (1000–1700 nm) are more favorable for photothermal therapy (PTT) therapeutic applications because of their greater depth of tissue penetration and better biosafety. However, the photothermal conversion efficiency (PCE) of the few NIR‐II‐responsive organic PTMs that have been investigated is still slightly low. Here, a stable alkyne‐bridged conjugated polymer, BBT‐BTE, are explored with a high PCE for tumor ablation within the NIR‐II window. The BBT‐BTE synthesized by the Stille coupling reaction has strong NIR‐II absorption, and their nanoparticles (NPs) achieved a 71% PCE under 1064 nm laser excitation, with good photothermal stability. BBT‐BTE NPs are shown to be effective in completely ablating tumors without any recurrence in both in vitro and in vivo experiments. Additionally, the biosafety of these NPs is further proven by biochemical analysis and tissue biopsy. This study developed a high‐performance NIR‐II PTM and offered practical and feasible insights into the design of efficient photothermal materials specifically for the NIR‐II window.

Plasmonic semi shells derived from simultaneous in situ gold growth and anisotropic acid etching of ZIF-8 for photothermal ablation of metastatic breast tumor

Open nanoshells such as nanobowls or nanocups collectively described as ‘semi shells’ have unique plasmonic properties due to their lack of symmetry. So far, their fabrication was based on multistep and laborious methods such as solid state sputter coating or selective deposition/etching using sacrificial templates. In this work, we report a rapid one step colloidal synthetic protocol for PEGylated semi-shell (SS) fabrication by simultaneous facet specific anisotropic chemical etching of rhombic dodecahedral ZIF-8 and heterogenous nucleation & growth of gold. The SS possesses a strong localized surface plasmon resonance in the near-infrared region, which is retained after surface passivation with polyethylene glycol and subsequent cryopreservation for extended shelf-life. Freshly reconstituted PEGylated SS was found to be safe & non-toxic in healthy C57BL/6 mice post intravenous administration. The PEGylated SS displayed significant photothermal efficiency of ~37% with 808 nm laser irradiation. Preclinical assessment of intra-tumoral photothermal efficacy indicated complete remission of primary breast tumor mass with insignificant metastasis to vital organs in 4T1 FL2 tumor bearing CD1 nude mice. Further, PEGylated SS mediated photothermal therapy also yielded morbidity free survivael of 75% for up to 90 days, indicating their potential to significantly improve outcomes in advanced breast tumors.

Breaking Barriers in Photothermal Tumor Therapy: A Cascade of Strain-Engineered Nanozyme in Action.

Cancer, a deadly and constantly evolving disease, has always been difficult to treat due to the complexity of the tumor microenvironment (TME). Cancer nanomedicines are proving to be a much better alternative for treatment due to their stability and ability to provide an efficient targeted therapy. An amorphous alloy bimetallene with an introduction of 2 % tensile strain with photothermal multiple enzyme-like catalytic activity is being presented here that functions as a TME-responsive nanozyme. Labeled as RhRu, this bimetallene, under acidic conditions, functions as oxidase (OXD) - like, peroxidase (POD) - like and catalase (CAT) - like enzymes, by producing radicals and disrupting the tumor cells. This effect is enhanced especially upon irradiation of laser and introduction of tensile strain in its heterophase boundaries. This current highlight discusses the strain engineering tactic of la-RhRu bimetallene and its potency as an anti-tumor therapeutic.

Transferrin-conjugated UiO-66 metal organic frameworks loaded with doxorubicin and indocyanine green: A multimodal nanoplatform for chemo-photothermal-photodynamic approach in cancer management

Stimuli-responsive nanoplatforms have been popular in controlled drug delivery research because of their ability to differentiate the tumor microenvironment from the normal tissue environment in a spatiotemporally controllable manner. The synergistic therapeutic approach of combining cancer chemotherapy with photothermal tumor ablation has improved the therapeutic efficacy of cancer therapeutics. In this study, a UiO-66 metal organic framework (MOF)-based system loaded with doxorubicin (DOX), surface decorated with the photothermal agents indocyanine green (ICG) and polydopamine (PDA), and conjugated with transferrin (TF) was successfully designed to operate as a responsive system to pH changes, featuring photothermal capabilities and target specificity for the purpose of treating breast cancer. The synthesized nanoplatform benefits from its uniform size, excellent DOX encapsulation efficiency (91.66 %), and efficient pH/NIR-mediated controlled release of the drug. In vitro photothermal studies indicate excellent photothermal stability of the formulation even after 6 on–off cycles of NIR irradiation. The in vitro cytotoxicity assessment using an NIR laser (808 nm) revealed that the DOX-loaded functionalized UiO-66 nanocarriers had outstanding inhibitory effects on 4T1 cells because of synergistic chemo-photo therapies, with no substantial toxicity by the carriers. In addition, cellular uptake evaluations revealed that UiO-DOX-ICG@PDA-TF could specifically target 4T1 cells on the basis of receptor-mediated internalization of transferrin receptors. Additionally, in vivo toxicity studies in Wistar rats indicated no signs of significant toxicity. The UiO-based nanoformulations effectively inhibited and destroyed cancer cells under 808 nm laser irradiation because of their minimal toxicity, strong biocompatibility, and outstanding synergistic chemo/photothermal/photodynamic treatment.

Glutathione-responsive biodegradable nanohybrid for cancer photoacoustic imaging and gas-assisted photothermal therapy

Photothermal therapy (PTT), particularly in the near-infrared-II (NIR-II) range, has attracted widespread attention over the past years. However, the accompanied inflammatory responses can result in undesirable side effects and contribute to treatment ineffectiveness. Herein, we introduced a novel biodegradable nanoplatform (CuS/HMON-PEG) capable of PTT and hydrogen sulfide (H2S) generation, aimed at modulating inflammation for improved cancer treatment outcomes. The embedded ultrasmall copper sulphide (CuS) nanodots (1–2 nm) possessed favorable photoacoustic imaging (PAI) and NIR-II photothermal capabilities, rendering CuS/HMON-PEG an ideal phototheranostic agent. Upon internalization by 4T1 cancer cells, the hollow mesoporous organosilica nanoparticle (HMON) component could react with the overproduced glutathione (GSH) to produce H2S. In addition to the anticipated photothermal tumor ablation and H2S-induced mitochondrial dysfunction, the anti-inflammatory regulation was also been demonstrated by the downregulation of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1beta (IL-1β). More importantly, the modulation of inflammation also promoted wound healing mediated by PTT. This work not only presents a H2S-based nanomodulator to boost NIR-II PTT but also provides insights into the construction of novel organic/inorganic hybrid nanosystems.

Genetic Engineering Bacillus thuringiensis Enable Melanin Biosynthesis for Anti-Tumor and Anti-Inflammation.

Collaboration between cancer treatment and inflammation management has emerged as an integral facet of comprehensive cancer care. Nevertheless, the development of interventions concurrently targeting both inflammation and cancer has encountered significant challenges stemming from various external factors. Herein, a bioactive agent synthesized by genetically engineering melanin-producing Bacillus thuringiensis (B. thuringiensis) bacteria, simultaneously achieves eco-friendly photothermal agent and efficient reactive oxygen/nitrogen species (RONS) scavenger benefits, perfectly tackling present toughies from inflammation to cancer therapies. The biologically derived melanin exhibits exceptional photothermal-conversion performance, facilitating potent photonic hyperthermia that effectively eradicates tumor cells and tissues, thereby impeding tumor growth. Additionally, the RONS-scavenging properties of melanin produced by B. thuringiensis bacteria contribute to inflammation reduction, augmenting the efficacy of photothermal tumor repression. This study presents a representative paradigm of genetic engineering in B. thuringiensis bacteria to produce functional agents tailored for diverse biomedical applications, encompassing inflammation and cancer therapy.

Docetaxel-Encapsulated Catalytic Pt/Au Nanotubes for Synergistic Chemo-Photothermal Therapy of Triple-Negative Breast Cancer.

The combination of photothermal therapy with chemotherapy has emerged as a promising therapeutic modality for addressing triple-negative breast cancer (TNBC). This manuscript describes a novel hybrid nanoplatform comprising ultrathin catalytic platinum/gold (Pt/Au) nanotubes encapsulated with docetaxel and phase-change materials (PCMs) for the photoacoustic imaging-guided synergistic chemo-photothermal therapy of TNBC. Upon irradiation of near-infrared laser, the photothermal heating of nanotubes converts solid-state PCM into liquid, triggering the controlled release of the encapsulated docetaxel. The thin Pt layer within nanotubes enhances the nanotube's thermal stability, thus prolonging the photothermal ablation of tumors. Furthermore, platinum effectively mitigates tumor hypoxia by catalyzing the decomposition of hydrogen peroxides to generate oxygen in the tumor microenvironment, thus improving the efficiency of chemotherapy. It is demonstrated that the drug-loaded nanotubes achieve significant tumor inhibition rates of 75.4% in vivo on 4T1 tumor-bearing mice, significantly surpassing control groups. These nanotubes also notably extend survival, attributable to the synergistic effects of prolonged photothermal therapy facilitated by platinum and oxygenation-enhanced chemotherapy. This combination leverages the unique properties of the Pt/Au NTs-DTX/PCM nanoplatform, optimizing therapeutic outcomes. It is envisioned that this nanoplatform may find important applications in managing superficial malignant solid tumors in general.

Synergistic Photothermal Tumor Immunotherapy by 1-MT Based on Zeolitic Imidazolate Framework-8 with pH-High Sensitivity.

A successful immune response against tumors depends on various cellular processes. Hence, there is an urgent need to construct a proficient nanoplatform for immunotherapy that can concurrently regulate the activities of various cells participating in the immune process. We have developed zeolitic imidazolate framework-8 (ZIF-8) formula, with good pH sensitivity, which is conducive to the release of drugs in the tumor site (acidic environment) and significantly improves immunotherapy. This is achieved through the coordinated action of different therapeutic agents, such as the photothermal agent polydopamine (PDA), the chemodrug camptothecin (CPT), and the immunomodulator 1-methyl-D-tryptophan (1-MT). In this study, we evaluated the antitumor effect of PDA/(CPT + 1-MT) @ZIF-8 (PCMZ) nanoparticles (NPs) in vitro and in vivo and investigated the molecular mechanism of PCMZ NPs in tumor suppression via photothermal-chemo-immunotherapy. MTT and Annexin V-FITC/PI double staining apoptosis test showed that PCMZ NPs could induce apoptosis of 4T1 cell, and PCMZ NPs could cause 4T1 cell necrosis under 808 nm laser irradiation. The objective is to establish a unilateral breast cancer model in mice and investigate the effect of PCMZ NPs on tumor growth and tumor suppression in tumor bearing mice. The results showed that PCMZ NPs showed good heating effect in vivo and effectively inhibited tumor growth under 808 nm laser irradiation. In addition, PCMZ NPs could induce the immunogenic death of tumor cells, promote the maturation of DCs, inhibit IDO pathway, and finally differentiate T cells into cytotoxic T cells and helper T cells, so as to effectively activate the anti-tumor immune response. The PCMZ NPs, possessing good photothermal conversion capabilities due to join of PDA, effectively overcome two main challenges in immunotherapy: insufficient stimulation of the immune response and evasion of the immune system. This provides a robust platform against invasive cancer and recurrent tumors.

Supramolecular Modulator Assisted Cryo-Engineered Porous Cu-DNA Nano-Vehicles for Versatile Theranostic Agent Delivery.

DNA nanotechnology combines structural design with therapeutic functions via programmable DNA motifs, but faces challenges in drug loading capacity. Herein a pore-engineering strategy is reported to develop a highly porous, universal DNA nano-vehicle through coordination self-assembly, cryo-engineering, and supramolecular chemistry, adapting to diverse cargo loading with desired theranostic agents. Thus, the complex synthesis and compatibility challenges typically associated with switching between different drug carriers are avoided. To this end, Cu2+ and nucleic acid therapeutic G3139 self-assemble into a prefabricated solid nanostructure, which subsequently undergoes ultrafast freezing and sublimation to introduce porosity, forming highly porous Cu-G3139 nanoparticles (CG NPs). The porous CG NPs efficiently accommodate diverse therapeutic molecules, from chemotherapeutics to non-chemotherapeutic agents, facilitated by positively-charged cyclodextrin. As a proof-of-concept, the photosensitizer indocyanine green (ICG) is loaded and coated with tannic acid (TA) to form CICG@TA, enabling remarkable photothermal and fluorescence imaging-guided synergistic tumor ablation. This work represents the first demonstration of sublimation-induced pore formation in metal-DNA hybrid nanoparticles without chemical etching, offering a scalable "plug-and-play" platform for personalized cancer therapy without redesign. This versatile pore-engineering strategy, merging supramolecular chemistry with cryo-engineered porosity, opens up new avenues for efficient, customized multidrug delivery for diverse tumor theranostic applications.

Pyrrolopyrrole Cyanine J-Aggregate Nanoparticles with High Near-Infrared Fluorescence Brightness and Photothermal Performance for Efficient Phototheranostics.

Advanced photosensitizers for high-performance fluorescence imaging-guided photothermal therapy demand excellent near-infrared (NIR) brightness [molar absorption coefficient (ε) × quantum yield (QY)] and exceptional photothermal performance [ε × photothermal conversion efficiency (PCE)]. However, integrating high brightness and potent photothermal performance within a single molecule faces a formidable challenge. This article proposes a method to address this issue by preparing J-aggregate nanoparticles (NPs) using molecules with high ε. J-aggregates effectively improve QY and induce molecular emission redshift, while high ε molecules play a crucial role in improving the brightness and photothermal performance. By optimizing the molecular structure based on the pyrrolopyrrole cyanine (PPCy), precise control over the QY and PCE of PPCy J-aggregates is achieved. Ultimately, PDDO NPs exhibiting superior brightness (ε × QY = 3.32 × 104 M-1 cm-1) and photothermal performance (ε × PCE = 1.21 × 105 M-1 cm-1) are identified as high-performance photosensitizers. Notably, each parameter represents one of the highest levels among the reported fluorescence or photothermal probes to date. The in vivo studies demonstrate that PDDO NPs possess exceptional NIR imaging capabilities and remarkable photothermal tumor inhibition rates. This study provides innovative insights into the development of high-performance multifunctional photosensitizers.

Self-Regenerating Photothermal Agents for Tandem Photothermal and Thermodynamic Tumor Therapy.

Small molecule-based photothermal agents (PTAs) hold promising future for photothermal therapy; however, unexpected inactivation exerts negative impacts on their application clinically. Herein, a self-regenerating PTA strategy is proposed by integrating 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS•+) with a thermodynamic agent (TDA) 2,2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH). Under NIR laser, the photothermal effect of ABTS•+ accelerates the production of alkyl radicals by AIPH, which activates the regeneration of ABTS•+, thus creating a continuous positive feedback loop between photothermal and thermodynamic effects. The combination of ABTS•+ regeneration and alkyl radical production leads to the tandem photothermal and thermodynamic tumor therapy. In vitro and in vivo experiments confirm that the synergistic action of thermal ablation, radical damage, and oxidative stress effectively realizes tumor suppression. This work offers a promising approach to address the unwanted inactivation of PTAs and provides valuable insights for optimizing combination therapy.

Isoindigo nanoparticles for photoacoustic imaging-guided tumor photothermal therapy

The key factor in photothermal therapy lies in the selection of photothermal agents. Traditional photothermal agents generally have problems such as poor photothermal stability and low photothermal conversion efficiency. Herein, we have designed and synthesized an isoindigo (IID) dye. We used isoindigo as the molecular center and introduced common triphenylamine and methoxy groups as rotors. In order to improve the photothermal stability and tumor targeting ability, we encapsulated IID into nanoparticles. As a result, the nanoparticles exhibited high photothermal stability and photothermal conversion efficiency (67%) upon 635 nm laser irradiation. Thus, the nanoparticles demonstrated a significant inhibitory effect on live tumors in photothermal therapy guided by photoacoustic imaging and provided a viable strategy to overcome the treatment challenges.

Tailored Covalent Organic Framework Platform: From Multistimuli, Targeted Dual Drug Delivery by Architecturally Engineering to Enhance Photothermal Tumor Therapy.

Engineering bulk covalent organic frameworks (COFs) to access specific morphological structures holds paramount significance in boosting their functions in cancer treatment; nevertheless, scant effort has been dedicated to exploring this realm. Herein, silica core-shell templates and multifunctional COF-based reticulated hollow nanospheres (HCOFs) are novelly designed as a versatile nanoplatform to investigate the simultaneous effect of dual-drug chemotherapy and photothermal ablation. Taking advantage of the distinct structural properties of the template, the resulting two-dimensional (2D) HCOF, featuring large internal voids and a peripheral interconnected mesoporous shell, presents intriguing benefits over its bulk counterparts for cancer treatment, including a well-defined morphology, an outstanding drug loading capability (99.6%) attributed to its ultrahigh surface area (2087 m2/g), great crystallinity, improved tumor accumulation, and an adjustable drug release profile. After being loaded with hydrophilic doxorubicin with a remarkable loading capacity, the obtained drug-loaded HCOFs were coated with gold nanoparticles (Au NPs) to confer them with three properties, including pore entrance blockage, active-targeting capability, and improved biocompatibility via secondary modification, besides high near infrared (NIR) absorption for efficient photothermal hyperthermia cancer suppression. The resultant structure was functionalized with mono-6-thio-β-cyclodextrin (β-CD) as a second pocket to load docetaxel as the hydrophobic anticancer agent (combination index = 0.33). The dual-drug-loaded HCOF displayed both pH- and near-infrared-responsive on-demand drug release. In vitro and in vivo evaluations unveiled the prominent synergistic performance of coloaded HCOF in cancer elimination upon NIR light irradiation. This work opens up a new avenue for exciting applications of structurally engineered HCOFs as hydrophobic/hydrophilic drug carriers as well as multimodal treatment agents.

A targeting multiple-stimuli responsive POSS-based smart nanomaterial for enhanced chemo-photothermal synergistic therapy

The combination of chemotherapy and photothermal therapy has garnered significant attention in the field of multimodal cancer therapy. However, achieving precise and controllable delivery of therapeutic agents remains a challenge. In this study, we designed a biocompatible smart nanomaterial (PSD-FA) for efficient loading of doxorubicin (DOX) through dynamic chemical bonding, with the aim of achieving responsive behavior to both the tumor microenvironment (TME) and external laser irradiation. The incorporation of PEG into the nanoplatform enhanced hydrophilicity of PSD-FA NPs. Folic acid (FA) served as a targeting ligand to guide the nanoparticles tumor sites. On one hand, SQ-N acted as an effective photothermal agent that efficiently converted light energy into heat energy upon stimulation by exogenous near-infrared light. This localized increase in temperature at the tumor site facilitated targeted killing of tumor cells. On the other hand, after photothermal therapy-induced tumor ablation, DOX was released in response to redox stimuli due to significantly higher concentrations of glutathione (GSH), an antioxidant presents in TME. This allowed deep penetration into the tumor tissue, expanding the attack area and inhibiting nucleic acid synthesis in tumor cells, ultimately leading to cell death. Both in vitro and in vivo experiments demonstrated excellent anticancer efficacy of PSD-FA NPs. Overall, this intelligent nanomaterial successfully achieved targeted drug delivery with redox-responsive release capabilities while synergistically combining chemo-photothermal therapies, thus exhibiting great potential for clinical applications.