Photothermal Therapy Treatment Research Articles

Autophagy Blockage Enhancing Photothermal and Chemodynamic Synergistic Therapy Based on HCQ/CuS Nanoplatform.

As an intracellular protective mechanism, autophagy has the potential to significantly impair the therapeutic effects of photothermal therapy (PTT) and chemodynamic therapy (CDT), which helps cancer cells survive under harsh conditions, such as high temperature and reactive oxygen species (ROS). In this study, an autophagy blockage enhanced PTT and CDT synergistic therapy nanoplatform is constructed by loading hydroxychloroquine (HCQ) with autophagy inhibitory effect into hollow copper sulfide (HCuS). Specifically, HCuS produces toxic ROS through Fenton-like reaction in the tumor microenvironment (TME). At the same time, PTT-mediated temperature elevation of the tumor region accelerates the Fenton-like reaction and ROS production, enhancing the therapeutic effect of CDT. Furthermore, the internal autophagy inhibitor HCQ significantly blocks the fusion of autophagosomes and lysosomes by deacidifying lysosomes, cutting off the self-protection mechanism of cancer cells, and amplifying the combined treatment of PTT and CDT. Both in vitro and in vivo results demonstrate that the combination of photothermal-enhanced chemodynamic therapy with inhibition of autophagy provides new insights into designing multifunctional therapeutic nanoagents.

Bactericidal Effect of Different Photochemical-Based Therapy Options on Implant Surfaces-An In Vitro Study.

Objectives: Photochemical systems are frequently recommended as an adjuvant treatment option in peri-implantitis therapy. The aim of the present study was to evaluate the efficacy of these treatment options, as well as a novel curcumin-based option, in a biofilm model on implants. Methods: Eighty dental implants were inoculated with an artificial biofilm of periodontal pathogens and placed in peri-implant pocket models. The following groups were analyzed: I, photodynamic therapy (PDT); II, PDT dye; III, curcumin/DMSO + laser; IV, curcumin/DMSO only; V, dimethyl sulfoxide (DMSO) only; VI, photothermal therapy (PTT); VII, PTT dye; VIII, control. After treatment, remaining bacterial loads were assessed microbiologically using quantitative real-time polymerase chain reaction analysis. Results: The PDT, PTT, and DMSO treatment methods were associated with statistically significant (p < 0.05) improvements in germ reduction in comparison with the other methods and the untreated control group. The mean percentage reductions were as follows: I (PDT) 93.9%, II (PDT dye) 62.9%, III (curcumin/DMSO + laser) 74.8%, IV (curcumin/DMSO only) 67.9%, V (DMSO) 89.4%, VI (PTT) 86.8%, and VII (PTT dye) 66.3%. Conclusions: The commercially available PDT and PTT adjuvant treatment systems were associated with the largest statistically significant reduction in periopathogenic bacteria on implant surfaces. However, activation with laser light at a suitable wavelength is necessary to achieve the bactericidal effects. The use of curcumin as a photosensitizer for 445 nm laser irradiation did not lead to any improvement in antibacterial efficacy in comparison with rinsing with DMSO solution alone.

Injectable Therapeutic Hydrogel with H2O2 Self-Supplying and GSH Consumption for Synergistic Chemodynamic/Low-Temperature Photothermal Inhibition of Postoperative Tumor Recurrence and Wound Infection.

Postoperative tumor recurrence and wound infection remain significant clinical challenges in surgery, often requiring adjuvant therapies. The combination treatment of photothermal therapy (PTT) and chemodynamic therapy (CDT) has proven to be effective in cancer treatment and wound infection. However, the hyperthermia during PTT increases the risk of normal tissue damage, severely impeding its application. Moreover, the efficacy of CDT is limited by insufficient hydrogen peroxide (H2O2) and excessive glutathione (GSH) levels at tumor or infection sites. Herein, an injectable and multifunctional CuO2@Au hydrogel system (CuO2@Au Gel) is developed for synergistic CDT and low-temperature PTT (LTPTT) to prevent tumor recurrence and bacterial wound infections. CuO2@Au Gel is constructed by embedding therapeutic CuO2@Au into low-melting point agarose hydrogel. In vitro and in vivo experiments confirm that the CuO2@Au in CuO2@Au Gel is capable of self-supplying H2O2 and depleting GSH, exhibiting effective CDT effect in acidic tumor or bacterial infected microenvironment. Additionally, it exhibits favorable photothermal conversion ability, inducing localized temperature elevation and synergistically enhancing CDT efficiency. The prepared CuO2@Au Gel demonstrates efficient tumor ablation capability in post-surgery recurrence mouse models and exhibits promising anti-infective efficiency in bacterial infection wound models, indicating significant potential in adjuvant therapy for post-surgical treatment and recovery.

NIR-II-Absorbing NDI Polymer with Superior Penetration Depth for Enhanced Photothermal Therapy Efficiency of Hepatocellular Carcinoma.

Hepatocellular carcinomas (HCC) have a high morbidity and mortality rate, and is difficult to cure and prone to recurrence when it has already developed. Therefore, early detection and efficient treatment of HCC is necessary. In this study, we synthesized a novel NDI polymer with uniform size, long-term stability, and high near-infrared two-zone (NIR-II) absorption efficiency, which can greatly enhance the effect of photothermal therapy (PTT) after intravenous injection into Huh-7-tumor bearing mice. The in vitro and in vivo studies showed that NDI polymer exhibited excellent NIR-guided PTT treatment, and the antitumor effect was approximately 88.5%, with obvious antimetastatic effects. This study developed an NDI polymer-mediated integrated diagnostic and therapeutic modality for NIR-II fluorescence imaging and photothermal therapy.

Biocompatible Copper-Based Nanocomposites for Combined Cancer Therapy.

Copper (Cu) and Cu-based nanomaterials have received tremendous attention in recent years because of their unique physicochemical properties and good biocompatibility in the treatment of various diseases, especially cancer. To date, researchers have designed and fabricated a variety of integrated Cu-based nanocomplexes with distinctive nanostructures and applied them in cancer therapy, mainly including chemotherapy, radiotherapy (RT), photothermal therapy (PTT), chemodynamic therapy (CDT), photodynamic therapy (PDT), cuproptosis-mediated therapy, etc. Due to the limited effect of a single treatment method, the development of composite diagnostic nanosystems that integrate chemotherapy, PTT, CDT, PDT, and other treatments is of great significance and offers great potential for the development of the next generation of anticancer nanomedicines. In view of the rapid development of Cu-based nanocomplexes in the field of cancer therapy, this review focuses on the current state of research on Cu-based nanomaterials, followed by a discussion of Cu-based nanocomplexes for combined cancer therapy. Moreover, the current challenges and future prospects of Cu-based nanocomplexes in clinical translation are proposed to provide some insights into the design of integrated Cu-based nanotherapeutic platforms.

Self-floating and long-term stable Ti3C2TX/polyurethane composite membranes with highly efficient photothermal conversion performances for multiple applications

Photothermal conversion has emerged as a highly effective method for converting solar energy into thermal energy for a variety of applications. In this study, we developed Ti3C2TX/PU membranes with exceptional photothermal conversion performance using a simple casting process. The Ti3C2TX/PU membranes are flexible, self-floating, and possess suitable strength and hydrophilicity. Additionally, they exhibit enhanced sunlight absorption capability and excellent thermal stability. When these membranes were applied for solar-driven seawater evaporation, they achieved an evaporation rate of 1.35 kg∙m−2 h−1 and a conversion efficiency of 84.85 % under 1 sun. In real outdoor conditions, they also displayed satisfactory evaporation performance. Impressively, the Ti3C2TX/PU membranes exhibited stable salt resistance and remarkable self-desalting properties, which are crucial for practical seawater evaporation applications. Furthermore, we observed that the photothermal performance of the Ti3C2TX/PU membranes improved with a higher Ti3C2TX content. Particularly noteworthy is the significant reduction in ice melting time when these membranes are wrapped around power wires, demonstrating their excellent photothermal deicing capabilities. The Ti3C2TX/PU membranes also showed promising application potential in low-temperature photothermal therapy treatment. We believe that such efficient and stable photothermal membranes will provide a sustainable solution for addressing challenges related to human health, life, and survival.

Promising two-dimensional rhenium diselenide nanosheets: Facile Preparation, characterization, in vivo tumor photoacoustic imaging and photothermal therapy

Nanoagent-mediated photothermal therapy (PTT) has been considered as an useful strategy for curing cancer. Nonetheless, identifying high-quality photothermal nanoagents with excellent biocompatibility testing, superior photothermal conversion efficiency (PTCE), and high treatment efficacy, is still a key dilemma for performing practical application in biomedicine field. In our work, a novel photothermal nanoagent named two-dimensional (2D) colloidal rhenium diselenide (ReSe2) nanosheets was exfoliated via a facile liqiud-assisted exfoliation approach. Owing to surface functionalization with poly-ethylene glycol (PEG), the obtained PEG-ReSe2 nanosheets demonstrated good solubility and excellent biocompatibility. Notably, the PEG-ReSe2 nanosheets showed excellent near infrared (NIR) photothermal activity. For the radiation of an NIR laser at 808 nm, an ultrahigh PTCE of 81.3% was demonstrated. Owing to its high Re element and good photoacoustic effect, the PEG-ReSe2 nanosheets can serve as good contrast nanoagents for in vivo photoacoustic (PA) imaging. Furthermore, the PEG-ReSe2 nanosheets acted as excellent photothermal agents (PTAs) for performing PTT. Thanks to high photothermal effects of PEG-ReSe2 nanosheets, in vitro photothermal effects showed that, the mortality rate of 4T1 cells was almost 100%. Meanwhile, in vivo experiments showed that mouse tumors were 100% ablated. More importantly, the PEG-ReSe2 nanosheets exhibited negligible levels of toxicity, as demonstrated by in vivo cytotoxicity assays and histological analysis. Finally, changes in micro-RNA expression level was proposed to assess PTT treatment efficacy of PEG-ReSe2 nanoagent. Interestingly, the miRNAs such as miR-125b-5p, miR-20a-5p, miR-214–3p, miR-221–3p, miR-212–3p and miR-27b-3p, were down-regulated. In addiiton, the miRNAs including miR-451a, miR200c-3p, and miR-let-7d-3p, were up-regulated. More importantly, these obtained miRNAs can work as typical indicators for screening PTT outcomes of PEG-ReSe2 nanosheets-involved PTT. Our research suggested that, the PEG-ReSe2 nanoagent may represent potential therapeutic nanoagents for in vivo photoacoustic imaging and cancer therapy.

Photoactivation Inducing Multifunctional Coupling of Fluorophore for Efficient Tumor Therapy In Situ.

Photoactivatable molecules, with high-precision spatialtemporal control, have largely promoted bioimaging and phototherapy applications of fluorescent dyes. Here, the first photoactivatable sensor (BI) is described that can be triggered by broad excitation light (405-660 nm), which further undergoes intersystem crossing and H-atom transfer processes to forming superoxide anion radicals (O2 -• ) and carbon radicals. Particularly, the photoinduced gain of carbon-centered radicals (BI•) allows for radical-radical coupling to afford the combined crosslink product (BI─BI), which would be oxidized in the presence of O2 -• to produce an extended conjugate system with near infrared emission (820 nm). Besides, the photochemically generated product (Cy─BI) possesses ultra-high photothermal conversion efficiency up to 90.9%, which optimized phototherapy potential. What's more, Western Blot assay reveals that both BI and the photoproduct Cy─BI can efficiently inhibit the expression of CHK1, and the irradiation of BI and Cy─BI further induces apoptosis and ultimately enhances the phototherapeutic effects. Thus, the combination of cell cycle block inducing apoptosis, photodynamic therapy and photothermal therapy treatments significantly suppress solid tumor in vivo antitumor efficacy explorations. This is a novel finding in developing photoactivatable molecules, as well as the broad applicability of photoimaging and phototherapy in tumor-related areas.

Dimerization extends π‐conjugation of electron donor‐acceptor structures leading to phototheranostic properties beyond the sum of two monomers

AbstractNear‐infrared (NIR)‐II fluorescence imaging‐guided photothermal therapy (PTT) has attracted great research interest, and constructing donor‐acceptor (D‐A) electronic configurations has become an established approach to lower bandgap and realize NIR‐II emission. However, very few π‐conjugated phototheranostic agents can realize efficient NIR‐II guided PTT using a clinically safe laser power density, implying that sufficient photothermal performance is still desired. In addition to the continuously refreshed photothermal conversion efficiency levels, the strategies that focus on enhancing light absorptivity have been rarely discussed and endow a new direction for enhancing PTT. Herein, a dimerization π‐extension strategy is raised to synthesize π‐conjugated dimers with A‐D‐A monomers. We observe that the light absorptivity (ε) of the dimers is strengthened three times owing to the enhanced electronic coupling effect as a result of the π‐conjugation extension, thereby surpassing the 2‐fold increase in chromophore numbers from the monomer to dimers. Thanks to the enhancement in light absorption, the dimers could generate much more photothermal heat than the monomer in in vivo PTT treatments. Therefore, an efficient anti‐tumor outcome has been fulfilled by using dimers under a low laser power (0.3 W/cm2). Moreover, the dimers with extended π‐conjugation structures become more favorable to the radiative excited state decay, thus exhibiting a distinguishing improvement in NIR‐II imaging compared with monomer. Collectively, due to the improved light absorptivity, the dimers can gain superior NIR‐II fluorescence brightness and photothermal performance over the recently reported material, which goes beyond the monomer in double doses for in vivo applications. All these results prove that dimerization is an effective strategy for designing high‐performance phototheranostic materials.

Structural engineering of mitochondria-targeted Au-Ag2S photosensitizers for enhanced photodynamic and photothermal therapy.

Much effort has been devoted to designing diverse photosensitizers for efficient photodynamic therapy (PDT) and photothermal therapy (PTT) performance. However, the effect of PS morphology on the PDT and PTT performance needs to be further explored. In this work, a photosensitizer, Au-Ag2S nanoparticles functionalized with indocyanine green, caspase-3 recognition peptides, and mitochondria-targeting peptides (AICM NPs) with different morphologies, including core-shell, eccentric core-shell-I, eccentric core-shell-II, and Janus morphologies, were synthesized to enhance PDT and PTT performance. Among them, AICM Janus NPs with enhanced charge-transfer efficiency and photothermal conversion demonstrate superior PDT and PTT performance compared to those of other morphologies. In addition, AICM NPs exhibit satisfactory surface-enhanced Raman scattering performance for in situ SERS monitoring of caspase-3 during PDT and PTT processes. After PDT and PTT treatment with AICM Janus NPs, the damaged mitochondria released caspase-3. AICM Janus NPs achieved a superior apoptosis rate in tumor cells in vitro. Furthermore, AICM Janus NPs treat the tumors in vivo within only 10 days, which is half the time reported in other work. The AICM NPs demonstrated superior therapeutic safety both in vitro and in vivo. This study investigates the effects of morphology-property-performance of photosensitizers on the PDT and PTT performances, which opens a new pathway toward designing photosensitizers for efficient PDT and PTT.

Photothermal therapy: a novel potential treatment for prostate cancer.

Prostate cancer (PCa) is a leading cause of cancer-related death in men, and most PCa patients treated with androgen deprivation therapy will progress to metastatic castration-resistant prostate cancer (mCRPC) due to the lack of efficient treatment. Recently, lots of research indicated that photothermal therapy (PTT) was a promising alternative that provided an accurate and efficient prostate cancer therapy. A photothermic agent (PTA) is a basic component of PPT and is divided into organic and inorganic PTAs. Besides, the combination of PTT and other therapies, such as photodynamic therapy (PDT), immunotherapy (IT), chemotherapy (CT), etc., provides an more efficient strategy for PCa therapy. Here, we introduce basic information about PTT and summarize the PTT treatment strategies for prostate cancer. Based on recent works, we think the combination of PPT and other therapies provides a novel possibility for PCa, especially CRPC clinical treatment.

Synthesis of organic photothermal agents for combined photothermal/enzymatic dynamic therapy of breast cancer

Nanoparticle-based photothermal therapy is an effective treatment for superficial tumors. However, due to the highly heterogeneous nature of breast cancer, photothermal therapy (PTT) used alone was unable to achieve satisfactory therapeutic results. Therefore, combining PTT with other therapies is a promising strategy for tumor treatment. Inspired by the significant elevation of lactate levels at the tumor site, we prepared a novel nanocomposite therapeutic platform (PPy-LOX) for combined PTT and enzyme dynamic treatment (EDT) of breast cancer. In detail, Polypyrrole (PPy) nanoparticles were synthesized using a simple chemical oxygenation method and polyvinylpyrrolidone (PVP) was used as a surface linker to enhance its colloidal stability. Further, the loading of lactate oxidase (LOX) is accomplished by simple physical mixing. The in vivo and in vitro results demonstrated the excellent biocompatibility of the synthesized PPy-LOX NPs. More importantly, PPy-LOX NPs has excellent photothermal conversion (η = 29.9%) and lactic acid catalytic ability. On the one hand, the temperature increase induced by near-infrared light irradiation can cause apoptosis of tumor cells; on the other hand, LOX can catalyze the generation of hydrogen peroxide from excess lactate in the tumor microenvironment to induce oxidative stress to kill tumor cells. In conclusion, the combination of PTT and EDT can effectively kill tumor cells. This work provides new ideas on how to design rational nanotherapeutic systems by exploiting the tumor microenvironment.

High-Strength Smart Microneedles with "Offensive and Defensive" Effects for Intervertebral Disc Repair.

Intervertebral disc degeneration (IVDD) is a global public health issue. The injury of annulus fibrosus (AF) caused by acupuncture or discectomy can trigger IVDD again. However, there is currently no suitable method for treating AF injury. In this study, the high-strength smart microneedles (MNs) which can penetrate the AF tissue through a local and minimally invasive method, and achieve remote control of speeded-up release of the drug and hyperthermia by the Near Infrared is developed. The PDA/GelMA composite MNs loaded with diclofenac sodium are designed to extracellularly "offend" the inflammatory microenvironment and mitigate damage to cells, and intracellularly increase the level of cytoprotective heat shock proteins to enhance the defense against the hostile microenvironment, achieving "offensive and defensive" effects. In vitro experiments demonstrate that the synergistic treatment of photothermal therapy and anti-inflammation effectively reduces inflammation, inhibits cell apoptosis, and promotes the synthesis of the extracellular matrix (ECM). In vivo experiments show that the MNs mitigate the inflammatory response, promote ECM deposition, reduce the level of apoptosis, and restore the biomechanical properties of the intervertebral disc (IVD) in rats. Overall, this high-strength smart MNs display promising "offensive and defensive" effects that can provide a new strategy for IVD repair.

Multifunctional AuPt Nanoparticles for Synergistic Photothermal and Radiation Therapy.

Photothermal therapy (PTT) has gained considerable interest as an emerging modality for cancer treatment in recent years. Radiation therapy (RT) has been widely used in the clinic as a traditional treatment method. However, RT and PTT treatments are limited by side effects and penetration depth, respectively. In addition, hypoxia within the tumor can lead to increased resistance to treatment. We synthesized multiple sizes of AuPt by modulating the reaction conditions. The smallest size of AuPt was selected and modified with folic acid (FA) for PTT and RT synergy therapy. Various methods including transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FITR) are used to determine the structure and composition of AuPt-FA (AF). In addition, we researched the photothermal properties of AF with IR cameras and infrared lasers. Flow cytometry, colony formation assays, CCK8, and fluorescent staining for probing the treatment effect in vitro. Also, we explored the targeting of AF by TEM and In Vivo Imaging Systems (IVIS). In vivo experiments, we record changes in tumor volume and weight as well as staining of tumor sections (ROS, Ki67, and hematoxylin and eosin). The AuPt with particle size of 16 nm endows it with remarkably high photothermal conversion efficiency (46.84%) and catalase activity compared to other sizes of AuPt (30 nm and 100 nm). AF alleviates hypoxia in the tumor microenvironment, leading to the production of more reactive oxygen species (ROS) during the treatment. In addition, the therapeutic effect was significantly enhanced by combining RT and PTT, with an apoptosis rate of 81.1% in vitro and an in vivo tumor volume reduction rate of 94.0% in vivo. These results demonstrate that AF potentiates the synergistic effect of PTT and RT and has the potential for clinical translation.

Glucose-responsive enzymatic biomimetic nanodots for H2O2 self-supplied catalytic photothermal/chemodynamic anticancer therapy

Photothermal therapy (PTT) combined with chemodynamic therapy (CDT) presents an appealing complementary anti-tumor strategy, wherein PTT accelerates the production of reactive oxygen species (ROS) in CDT and CDT eliminates residual tumor tissues that survive from PTT treatment. However, nanomaterials utilized in PTT/CDT are limited by non-specific damage to the entire organism. Herein, a glucose-responsive enzymatic Fe@HRP-ABTS/GOx nanodot is judiciously designed for tumor-specific PTT/CDT via a simple and clean protein-templated biomimetic mineralization synthesis. By oxidizing glucose in tumor cells, glucose oxidase (GOx) activates glucose-responsive tumor therapy and increases the concentration of H2O2 at the tumor site. More importantly, the self-supplied peroxide hydrogen (H2O2) can convert ABTS (2,2′-Hydrazine-bis(3-ethylbenzothiazoline-6-sulfonic acid) diamine salt) into oxidized ABTS (oxABTS) through horseradish peroxidase (HRP) catalysis for PTT and photoacoustic (PA) imaging. Furthermore, the Fe2+ arising from the reduction of Fe3+ by overexpressed GSH reacts with H2O2 to generate intensely reactive •OH through the Fenton reaction, concurrently depleting GSH and inducing efficient tumor CDT. The in vitro and in vivo experiments demonstrate superior cancer cell killing and tumor eradication effect of Fe@HRP-ABTS/GOx nanodot under near-infrared (NIR) laser irradiation. Collectively, the nanodots provide mutually reinforcing catalytic PTT/CDT anti-tumor strategies for treating liver cancer and potentially other malignancies. Statement of significanceCombinatorial antitumor therapy with nanomedicines presents great prospects for development. However, the limitation of non-specific damage to normal tissues hinders its further clinical application. In this work, we fabricated tumor-selective biomimetic Fe@HRP-ABTS/GOx nanodots for H2O2 self-supplied catalytic photothermal/chemodynamic therapy of tumors. The biomimetic synthesis strategy provides the nanodots with enzymatic activity in response to glucose to produce H2O2. The self-supplied H2O2 initiates photothermal therapy with oxidized ABTS and enhances chemodynamic therapy through simultaneous •OH generation and GSH depletion. Our work provides a new paradigm for developing tumor-selective catalytic nanomedicines and will guide further clinical translation of the enzymatic biomimetic synthesis strategy.

Blockage of HSP90 and IDO1 pathway by α-MSH modified nanoelicitor to dual-facilitate mild photothermal therapy

Mild photothermal therapy (PTT) kills tumors at low temperatures (<45 ​°C) with less non-specific thermal diffusion through adjacent normal tissues, making it a promising antitumor strategy. Although mild PTT can directly convert light energy into heat to kill tumors and indirectly induce immune cell death to prime the immune response, it simultaneously induces negative regulatory factors in the body to resist antitumor functions. In particular, the direct killing effects were reversed by the upregulation of heat shock protein 90 (HSP90) induced by mild PTT. The antitumor effects of T-cell-based immunotherapy counter indoleamine 2,3-dioxygenase1 (IDO1)-catalyzed kynurenine accumulation. Current studies have mainly focused on promoting direct killing effects or utilizing the priming immune response to strengthen the immunotherapy of mild PTT. Therefore, it is necessary to investigate whether the simultaneous promotion of direct killing and indirect immune activation would synergistically maximize mild PTT efficacy. This study reports on the development of a tumor-targeting nanoelicitor, α-MSH-GA/IR780/1-MT-Liposome (M-GIM-Lip), by co-loading the photothermal agent IR780, HSP90 inhibitor geldanamycin, and IDO1 inhibitor 1-MT into liposomes with a melanoma-specific target ligand α-MSH modification. After accumulating in the tumor, the M-GIM-Lip could significantly inhibit tumor progress by combinate blockage of HSP90 and IDO1 pathways at 41 ​°C treatment of mild PTT. The study offers an innovative co-regulation strategy for enhancing the antitumor effects of mild PTT.

Injectable Hydrogel Containing TiO Nanosheets for Synergistic Photothermal/Thermodynamic Therapy.

Tumors have become the biggest obstacle to human health, and there are various treatment methods at present. Photothermal therapy (PTT) is usually ineffective and does not inhibit tumor progression due to the inability of the lasers to penetrate deeply. Therefore, most existing studies chose a 1064 nm laser with stronger penetrating power; meanwhile, studies have shown that the inclusion of harmful free radicals can significantly improve the antitumor efficacy. Herein, TiO nanosheets (NSs) were creatively prepared and encapsulated with an alkyl radical generator {2,2'-azobis[2-(2-imidazoline-2-yl)propane] dihydrochloride, [AIPH]} in sodium alginate (ALG) hydrogel for effective tumor killing by PTT and pairing with dangerous free radicals. TiO NSs were obtained by the liquid-phase exfoliation method, together with AIPH, which were in situ coencapsulated multifunctional hydrogels formed by the combination of Ca2+ and ALG. This ALG hydrogel could enrich TiO NSs and AIPH at the tumor site for a long time, and through the excellent photothermal properties of TiO NSs, AIPH could slowly and effectively generate alkyl radicals at the tumor site, which, in turn, gave it a better antitumor effect compared with that of TiO NSs in the deep hypoxic environment of the tumor. The AIPH + TiO + ALG hydrogel has distinctive anticancer capabilities based on the results of both in vivo and in vitro experiments. This material also has good biosafety. By combining PTT and free radical treatment, this work provides a novel therapeutic method to achieve oxygen-independent free radical production and enhance therapeutic efficacy.

Cascade Amplification of Pyroptosis and Apoptosis for Cancer Therapy through a Black Phosphorous-Doped Thermosensitive Hydrogel.

Cell pyroptosis has a reciprocal relationship with various cancer treatment modalities such as chemotherapy. However, the tumor microenvironment, characterized by hypoxia, substantially restricts the development and application of tumor therapies that integrate cell pyroptosis. Therefore, the cascade amplification of oxidative stress by interfering with redox homeostasis in tumors may be a promising approach. In this study, black phosphorus (BP) nanosheets and a glutathione peroxidase 4 inhibitor (RSL3) were coloaded into a thermosensitive PDLLA-PEG-PDLLA (PLEL) hydrogel (RSL3/BP@PLEL). Owing to the photothermal property of BP nanosheets, the RSL3/BP@PLEL hydrogel may trigger the release of loaded drugs in a more controllable and on-demand manner. Investigation of the antitumor effect in a mouse liver tumor model demonstrated that local injection of the hydrogel formulation in combination with near infrared laser irradiation could efficiently suppress tumor growth by interfering with the redox balance in tumors. Mechanistic study indicated that the combined treatment of photothermal therapy and glutathione depletion based on this hydrogel efficiently induced cell pyroptosis through both caspase-1/GSDMD and caspase-3/GSDME pathways, thereby triggering the repolarization of tumor-associated macrophages from M2 to M1. Overall, we developed a biocompatible and biodegradable hydrogel formulation for application in combination cancer treatment, providing a new platform for enhancing the efficacy of cancer therapy by amplifying cell pyroptosis and apoptosis.

Efficient Drug Delivery of Ti3C2Tx MXenes for Synergistic Treatment of Human Hypopharyngeal Squamous Cell Carcinoma.

Ti3C2Tx MXene is a versatile two-dimensional material that exhibits exceptional properties, such as an abundance of surface functional groups that facilitate modifications. Additionally, Ti3C2Tx MXene possesses remarkable photothermal effects. In this study, ultrathin Ti3C2Tx nanosheets with dimensions (∼200 nm) suitable for biological applications were prepared by ultrasonication of larger pieces of Ti3C2Tx MXene with a cell pulverizer operating at a specific power. The ultrathin nanosheets exhibited a significant photothermal conversion efficiency (47.1%) under an 808 nm infrared laser irradiation. In addition, they showed an excellent mass extinction coefficient of 15.7 L g-1 cm-1. By exploiting the intermolecular force between these ultrathin nanosheets and doxorubicin (DOX), a drug loading efficiency of 72.8% was achieved. Through layer-by-layer surface modification of a sulfhydryl-modified polymethacrylic acid (PMAsh) shell and a transferrin (Tf) layer with targeting function, a multifunctional nanomedicine platform (Ti3C2Tx-DOX-PMAsh-Tf) was constructed. Experiments executed in vitro with cells and in vivo to inhibit tumors manifested that Ti3C2Tx is biocompatible. Furthermore, the results showed that the drug release behavior of Ti3C2Tx-DOX-PMAsh-Tf is responsive to glutathione (GSH) stimulation. The synergistic treatment of photothermal therapy and the anticancer drug DOX effectively achieved the inhibition of human hypopharyngeal squamous cell carcinoma.

ALA/Ag2S/MnO2 Hybrid Nanoparticles for Near-Infrared Image-Guided Long-Wavelength Phototherapy of Breast Cancer.

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) based on temperature increase and the formation of reactive oxygen species (ROS), respectively, is an exciting avenue to provide local and improved therapy of tumors with minimal off-site toxicity. 5-Aminolevulinic acid (ALA) is one of the most popular PDT pro-drugs, and its efficiency improves significantly when delivered to tumors with nanoparticles (NPs). But the tumor site's hypoxic environment is a handicap for the oxygen-consuming PDT process. In this work, highly stable, small, theranostic NPs composed of Ag2S quantum dots and MnO2, electrostatically loaded with ALA, were developed for enhanced PDT/PTT combination of tumors. MnO2 catalyzes endogenous H2O2 to O2 conversion and glutathione depletion, enhancing ROS generation and ALA-PDT efficiency. Ag2S quantum dots (AS QDs) conjugated with bovine serum albumin (BSA) support MnO2 formation and stabilization around Ag2S. AS-BSA-MnO2 provided a strong intracellular near-infrared (NIR) signal and increased the solution temperature by 15 °C upon laser irradiation at 808 nm (215 mW, 10 mg/mL), proving the hybrid NP as an optically trackable, long-wavelength PTT agent. In the in vitro studies, no significant cytotoxicity was observed in the absence of laser irradiation in healthy (C2C12) or breast cancer cell lines (SKBR3 and MDA-MB-231). The most effective phototoxicity was observed when AS-BSA-MnO2-ALA-treated cells were co-irradiated for 5 min with 640 nm (300 mW) and 808 nm (700 mW) due to enhanced ALA-PDT combined with PTT. The viability of cancer cells decreased to approximately 5-10% at 50 μg/mL [Ag], corresponding to 1.6 mM [ALA], whereas at the same concentration, individual PTT and PDT treatments decreased the viability to 55-35%, respectively. The late apoptotic death of the treated cells was mostly correlated with high ROS levels and lactate dehydrogenase. Overall, these hybrid NPs overcome tumor hypoxia, deliver ALA to tumor cells, and provide both NIR tracking and enhanced PDT + PTT combination therapy upon short, low-dose co-irradiation at long wavelengths. These agents that may be utilized for treating other cancer types are also highly suitable for in vivo investigations.