Photothermal Cancer Therapy Research Articles

Multishaped bio-gold polyphenols bearing nanoparticles to promote inflammatory suppression

Green synthesis from plant waste involves the generation of functional nanoparticles (NPs), offering significant potential for a wide range of applications. Numerous studies have focused on the use of plant extracts to produce AuNPs suitable for various applications in the medical field, particularly in photothermal therapy and cancer therapy, owing to their plasmonic properties. Moreover, NP-mediated immunostimulation and immunosuppression is an intriguing field of research, focusing on how manipulation of NP physicochemical properties can influence their inter-action with immune cells and immune modulation. However, to date, few investigations have been conducted on the modulation of the inflammatory response mediated by green-synthesized nanostructures. To this aim, we synthesized AuNPs using extracts of Laurus nobilis, which exhibit high crystallinity and are inherently coated by a dense network of polyphenols, thus maintaining stability on their surface through the green synthesis approach. Then, in order to explore how these green-synthesized nanostructures can enhance or suppress the inflammatory cellular responses, we investigated the response of free polyphenols and AuNPs@polyphenols in murine bone marrow derived dendritic cells (BMDCs), by means of morphomechanical analysis and biochemical assays. Our findings demonstrated that DCs exposed to both free polyphenol extract and AuNPs@polyphenols were able to inhibit the secretion of crucial inflammatory mediators in response to lipopolysaccharide (LPS) administration. Therefore, polyphenols immobilized on Au surface were more effective in the inflammation suppression. These evidence paving the way for a powerful strategy to develop edible anti-inflammatory adjuvants, overcoming the limitations associated with the use of free polyphenols in clinical practice.

Laser-activable murine ferritin nanocage for chemo-photothermal therapy of colorectal cancer

Chemotherapy, as a conventional strategy for tumor therapy, often leads to unsatisfied therapeutic effect due to the multi-drug resistance and the serious side effects. Herein, we genetically engineered a thermal-responsive murine Ferritin (mHFn) to specifically deliver mitoxantrone (MTO, a chemotherapeutic and photothermal agent) to tumor tissue for the chemotherapy and photothermal combined therapy of colorectal cancer, thanks to the high affinity of mHFn to transferrin receptor that highly expressed on tumor cells. The thermal-sensitive channels on mHFn allowed the effective encapsulation of MTO in vitro and the laser-controlled release of MTO in vivo. Upon irradiation with a 660 nm laser, the raised temperature triggered the opening of the thermal-sensitive channel in mHFn nanocage, resulting in the controlled and rapid release of MTO. Consequently, a significant amount of reactive oxygen species was generated, causing mitochondrial collapse and tumor cell death. The photothermal-sensitive controlled release, low systemic cytotoxicity, and excellent synergistic tumor eradication ability in vivo made mHFn@MTO a promising candidate for chemo-photothermal combination therapy against colorectal cancer.Graphical

Neutral Cyanine: Ultra-Stable NIR-II Merocyanines for Highly Efficient Bioimaging and Tumor-Targeted Phototheranostics.

Fluorescence imaging (FLI)-guided phototheranostics using emission from the second near-infrared (NIR-II) window show significant potential for cancer diagnosis and treatment. Clinical imaging-used polymethine ionic indocyanine green (ICG) dye is widely adopted for NIR fluorescence imaging-guided photothermal therapy (PTT) research due to its exceptional photophysical properties. However, ICG has limitations such as poor photostability, low photothermal conversion efficiency (PCE), short-wavelength emission peak, and liver-targeting issues, which restrict its wider use. In this study, two ionic ICG derivatives are transformed into neutral merocyanines (mCy) to achieve much-enhanced performance for NIR-II cancer phototheranostics. Initial designs of two ionic dyes show similar drawbacks as ICG in terms of poor photostability and low photothermal performance. One of the modified neutral molecules, mCy890, shows significantly improved stability, an emission peak over 1000nm, and a high photothermal PCE of 51%, all considerably outperform ICG. In vivo studies demonstrate that nanoparticles of the mCy890 can effectively accumulate at the tumor sites for cancer photothermal therapy guided by NIR-II fluorescence imaging. This research provides valuable insights into the development of neutral merocyanines for enhanced cancer phototheranostics.

Three musketeers of PDA-based MRI contrasting and therapy

Polydopamine (PDA) stands as a versatile material explored in cancer nanomedicine for its unique properties, offering opportunities for multifunctional drug delivery platforms. This study explores the potential of utilizing a one-pot synthesis to concurrently integrate Fe, Gd and Mn ions into porous PDA-based theranostic drug delivery platforms called Ferritis, Gadolinis and Manganis, respectively. Our investigation spans the morphology, magnetic properties, photothermal characteristics and cytotoxicity profiles of those potent nanoformulations. The obtained structures showcase a spherical morphology, robust magnetic response and promising photothermal behaviour. All of the presented nanoparticles (NPs) display pronounced paramagnetism, revealing contrasting potential for MRI imaging. Relaxivity values, a key determinant of contrast efficacy, demonstrated competitive or superior performance compared to established, used contrasting agents. These nanoformulations also exhibited robust photothermal properties under near infra-red irradiation, showcasing their possible application for photothermal therapy of cancer. Our findings provide insights into the potential of metal-doped PDA NPs for cancer theranostics.

Experimental investigation of photothermal conversion and thermal conductivity of broadband absorbing gold nanoblackbodies and graphene oxide nanoparticles for plasmonic photothermal cancer therapy

The choice of nanomaterial is crucial for achieving desired thermal ablation of a tumors, considering nanoparticle dose/concentration and near-infrared (NIR) irradiation parameters during plasmonic photothermal therapy (PPTT). Most studies prioritize use of nanoparticles with high photothermal conversion efficiency (η) for PPTT without emphasizing the thermal conductivity (κ) within a solid tumor. Herein, two broadband absorbing nanoparticles, i.e., gold nanoblackbodies (AuNBs) and graphene oxide (GO) nanoparticles, are compared for η under similar NIR irradiation and nanoparticles dose. Further, the effect of photothermal conversion and κ are studied through tumor-tissue mimicking phantoms mimicking invasive ductal carcinoma embedded with nanoparticles, surrounded by normal tissue region. Under similar conditions, η is higher in AuNBs (73.2%) than GO nanoparticles (63.7%), while κ of GO nanoparticles embedded phantom (0.62 W/mK) surpasses AuNBs embedded phantom (0.59 W/mK) by 5.08%. Photothermal response through tumor-tissue mimicking phantoms shows that GO nanoparticles achieve higher temperatures within the entire tumor region than AuNBs due to their high κ, despite having lower η. This finding suggests that η is not the sole parameter, and it is the coupled effect of η and κ for the choice/suitability of a nanoparticle to attain desired temperatures throughout the tumor for PPTT.

Structure-Inherent Tumor-Targeted IR-783 for Near-Infrared Fluorescence-Guided Photothermal Therapy.

IR-783, a commercially available near-infrared (NIR) heptamethine cyanine dye, has been used for selective tumor imaging in breast, prostate, cervical, and brain cancers in vitro and in vivo. Although the molecular mechanism behind the structure-inherent tumor targeting of IR-783 has not been well-demonstrated, IR-783 has unique properties such as a good water solubility and low cytotoxicity compared with other commercial heptamethine cyanine dyes. The goal of this study is to evaluate the phototherapeutic efficacy of IR-783 as a tumor-targeted photothermal agent in human colorectal cancer xenografts. The results demonstrate that IR-783 shows both the subcellular localization in HT-29 cancer cells and preferential accumulation in HT-29 xenografted tumors 24 h after its intravenous administration. Furthermore, the IR-783 dye reveals the superior capability to convert NIR light into heat energy under 808 nm NIR laser irradiation in vitro and in vivo, thereby inducing cancer cell death. Taken together, these findings suggest that water-soluble anionic IR-783 can be used as a bifunctional phototherapeutic agent for the targeted imaging and photothermal therapy (PTT) of colorectal cancer. Therefore, this work provides a simple and effective approach to develop biocompatible, hydrophilic, and tumor-targetable PTT agents for targeted cancer phototherapy.

NIR-Responsive Methotrexate-Modified Iron Selenide Nanorods for Synergistic Magnetic Hyperthermic, Photothermal, and Chemodynamic Therapy.

Breast cancer is a malignant tumor with a high mortality rate among women. Therefore, it is necessary to develop novel therapies to effectively treat this disease. In this study, iron selenide nanorods (FeSe2 NRs) were designed for use in magnetic hyperthermic, photothermal, and chemodynamic therapy (MHT/PTT/CDT) for breast cancer. To illustrate their efficacy, FeSe2 NRs were modified with the chemotherapeutic agent methotrexate (MTX). MTX-modified FeSe2 (FeSe2-MTX) exhibited excellent controlled drug release properties. Fe2+ released from FeSe2 NRs induced the release of •OH from H2O2 via a Fenton/Fenton-like reaction, enhancing the efficacy of CDT. Under alternating magnetic field (AMF) stimulation and 808 nm laser irradiation, FeSe2-MTX exerted potent hyperthermic and photothermal effects by suppressing tumor growth in a breast cancer nude mouse model. In addition, FeSe2 NRs can be used for magnetic resonance imaging in vivo by incorporating their superparamagnetic characteristics into a single nanomaterial. Overall, we presented a novel technique for the precise delivery of functional nanosystems to tumors that can enhance the efficacy of breast cancer treatment.

NIR-II Absorbed Dithienopyrrole-Benzobisthiadiazole Based Nanosystems for Autophagy Inhibition and Calcium Overload Enhanced Photothermal Therapy.

Although the current cancer photothermal therapy (PTT) can produce a powerful therapeutic effect, tumor cells have been proved a protective mechanism through autophagy. In this study, a novel hybrid theranostic nanoparticle (CaCO3@CQ@pDB NPs, CCD NPs) is designed and prepared by integrating a second near-infrared (NIR-II) absorbed conjugated polymer DTP-BBT (pDB), CaCO3, and autophagy inhibitor (chloroquine, CQ) into one nanosystem. The conjugated polymer pDB with asymmetric donor-acceptor structure shows strong NIR-II absorbing capacity, of which the optical properties and photothermal generation mechanism of pDB are systematically analyzed via molecular theoretical calculation. Under NIR-II laser irradiation, pDB-mediated PTT can produce powerful killing ability to tumor cells. At the same time, heat stimulates a large amount of Ca2+ inflow, causing calcium overload induced mitochondrial damage and enhancing the apoptosis of tumor cells. Besides, the released CQ blocks the self-protection mechanism of tumor cells and greatly enhances the attack of PTT and calcium overload therapy. Both in vitro and in vivo experiments confirm that CCD NPs possess excellent NIR-II theranostic capacity, which provides a new nanoplatform for anti-tumor therapy and builds great potential for future clinical research.

Ti3C2Tx MXene nanosheet-based drug delivery/cascaded enzyme system for combination cancer therapy and anti-inflammation

Photothermal therapy (PTT)-based combination therapy is an effective approach to cancer treatment. However, there is a possibility of tumor development due to the inflammation caused by PTT. In addition, hyperthermia can cause damage to normal tissues. This work reported a drug delivery/cascade enzyme system based on Ti3C2Tx MXene nanosheets. Ultra-small, degradable mesoporous silica nanoparticles (DS-MSN) were prepared to load phloretin (Phl), which has anti-inflammatory, antioxidant, and anticancer properties. Subsequently, glucose oxidase (GOx) was adsorbed on the surface of DS-MSN. The nanoparticles were then modified on Ti3C2Tx MXene nanosheets and finally treated with polyethylene glycol (PEG) to obtain the multifunctional system named Ti3C2Tx-Phl@DS-MSN-GOx-PEG (TPDMGP). The high near-infrared photothermal conversion efficiency of Ti3C2Tx made it suitable for PTT. GOx and Ti3C2Tx formed a cascade enzyme system inside cancer cells: Ti3C2Tx exhibited catalase (CAT)-like activity that decomposed intracellular hydrogen peroxide (H2O2) into O2, which was provided to GOx for enhanced starvation therapy. GOx in the presence of O2 produces H2O2, for the oxygen production of Ti3C2Tx. Meanwhile, DS-MSN could be degraded in the reducing environment inside cancer cells as it contains disulfide bonds in its backbone, thus releasing Phl for chemotherapy. Such a combination therapy strategy could achieve a satisfactory therapeutic outcome by low-temperature PTT while evading normal tissue damage by high temperature. The anti-inflammatory effects of both Ti3C2Tx and Phl enabled TPDMGP to eliminate the inflammation caused by PTT via the scavenging of reactive oxygen species (ROS). The multifunctional system is expected to generate new paradigms for cancer PTT.

Abstract PO5-27-08: Cytotoxicity and motility inhibitory effect of FA-Hep-CuS nanoparticles on breast cancer cells

Abstract In spite of a decreased rate of cancer onset, by about 33%, since 1991, it is still as dreadful and a major cause of death globally. After heart disease, cancer continues to be the second most prevalent cause of death in the US. According to the American Cancer Society, there will be around 2 million new cases of cancer identified in Americans in 2023, along with approximately 610,000 cancer-related deaths. Breast cancer will continue to be the most common invasive cancer diagnosed in women. Each year about 2.3 million women are diagnosed with breast cancer. In consideration of the severity of breast cancer, herein we designed and synthesized a multimode photothermal agent, FA-Hep-CuS, for the advancement of photothermal therapy of cancer. CuS nanoparticles deposited on heparin-conjugated folic acid (FA-Hep-CuS) were prepared by gently heating unfractionated heparin in dimethyl formamide (DMF), then adding N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (EDC), and finally adding the aminated folic acid in DMF and stirring for four days. Further, FA-Hep was dispersed in DI water, then citrated CuS nanoparticles dispersed in DI water were added, and the mixture was stirred for 8 hours to prepare FA-Hep-CuS. Moreover, the activation of the nanoparticles by non-ionizing radiation (NIR; l= 808 nm) was also evaluated for increased anti-cancer efficiency. In MDA-MB-231 (Triple-negative or TNBC or ER⁻/PR⁻/Her2⁻) breast cancer cell lines, the cytotoxic effects of FA, CuS, and FA-Hep-CuS, as well as their ability to impede motility, have been investigated. They have also been examined to determine how they affect the expression of mesenchymal indicators and clonogenicity. All these demonstrated significant dose-dependent in-vitro cytotoxicity against MDA-MB- 231 breast cancer cells. The cell viability assay showed that the FA-CuS was more effective than FA and CuS. Activation of the nanoparticles with NIR resulted in the significantly enhanced dose-dependent inhibitory potential of the nanoparticles against the migratory properties of the aggressive TNBC cells. In agreement, the clonogenicity of the TNBC cells was also inhibited dose-dependently. We are now focusing on its inhibitory potential on the EMT markers of the TNBC cells. We further aim to investigate the effects of FA-Hep-CuS in in-vivo models of breast cancers. Citation Format: David Arreola. Cytotoxicity and motility inhibitory effect of FA-Hep-CuS nanoparticles on breast cancer cells [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-27-08.

Chasing Graphene-Based Anticancer Drugs: Where are We Now on the Biomedical Graphene Roadmap?

Graphene and graphene-based materials have attracted growing interest for potential applications in medicine because of their good biocompatibility, cargo capability and possible surface functionalizations. In parallel, prototypic graphene-based devices have been developed to diagnose, imaging and track tumor growth in cancer patients. There is a growing number of reports on the use of graphene and its functionalized derivatives in the design of innovative drugs delivery systems, photothermal and photodynamic cancer therapy, and as a platform to combine multiple therapies. The aim of this review is to introduce the latest scientific achievements in the field of innovative composite graphene materials as potentially applied in cancer therapy. The "Technology and Innovation Roadmap" published in the Graphene Flagship indicates, that the first anti-cancer drugs using graphene and graphene-derived materials will have appeared on the market by 2030. However, it is necessary to broaden understanding of graphene-based material interactions with cellular metabolism and signaling at the functional level, as well as toxicity. The main aspects of further research should elucidate how treatment methods (e.g., photothermal therapy, photodynamic therapy, combination therapy) and the physicochemical properties of graphene materials influence their ability to modulate autophagy and kill cancer cells. Interestingly, recent scientific reports also prove that graphene nanocomposites modulate cancer cell death by inducing precise autophagy dysfunctions caused by lysosome damage. It turns out as well that developing photothermal oncological treatments, it should be taken into account that near-infrared-II radiation (1000-1500 nm) is a better option than NIR-I (750-1000 nm) because it can penetrate deeper into tissues due to less scattering at longer wavelengths radiation.

Camptothecin-loaded and IR780-doped polydopamine nanomedicine used for multifunctional chemo-photothermal-photodynamic therapy for lung cancer

Lung cancer poses a major threat to human health. Camptothecin (CPT), a cytotoxic alkaloid derived from pyrroloquinoline, ranks alongside paclitaxel as the most widely studied natural broad-spectrum antitumor drug. However, poor water solubility and instability of the lactone ring hinder its clinical application. To improve the efficacy of CPT in lung cancer, we developed a polydopamine (PDA) nanoparticle formulation combined with photothermal therapy (PTT). Although PDA nanocrystals have good biocompatibility and excellent PTT conversion ability, their high-temperature PTT application tends to adversely affect normal tissues. By doping the surface of PDA nanoparticles with IR780, a near-infrared photosensitiser, a CPT-loaded PDA nanoparticle (CPT-PDA-IR780) was designed that was easy to modify and had strong adhesion. This formulation was used for lung cancer treatment. Due to the incorporation of a photosensitiser, CPT-PDA-IR780 nanomaterials showed better low temperature PTT properties and demonstrated significant anti-lung cancer effects both in vivo and in vitro. By combining chemotherapy and photodynamic therapy (PDT), this nanomedicine achieved better efficacy in low-temperature PTT for lung cancer. These findings provide a scientific basis for the development of CPT nanomaterials and for the treatment of lung cancer with low-temperature PTT through combination therapy.

Dynamic tracking of onion-like carbon nanoparticles in cancer cells using limited-angle holographic tomography with self-supervised learning

This research presents a novel approach for the dynamic monitoring of onion-like carbon nanoparticles inside colorectal cancer cells. Onion-like carbon nanoparticles are widely used in photothermal cancer therapy, and precise 3D tracking of their distribution is crucial. We proposed a limited-angle digital holographic tomography technique with unsupervised learning to achieve rapid and accurate monitoring. A key innovation is our internal learning neural network. This network addresses the information limitations of limited-angle measurements by directly mapping coordinates to measured data and reconstructing phase information at unmeasured angles without external training data. We validated the network using standard SiO2 microspheres. Subsequently, we reconstructed the 3D refractive index of onion-like carbon nanoparticles within cancer cells at various time points. Morphological parameters of the nanoparticles were quantitatively analyzed to understand their temporal evolution, offering initial insights into the underlying mechanisms. This methodology provides a new perspective for efficiently tracking nanoparticles within cancer cells.

Eco-friendly Synthesis of WO3 Nanostructures for Near-Infrared Laser Improved Photothermal Therapy of Breast Cancer

Eco-friendly Synthesis of WO3 Nanostructures for Near-Infrared Laser Improved Photothermal Therapy of Breast Cancer

Cell Membrane-Coated Biomimetic Nanoparticles in Cancer Treatment.

Nanoparticle-based drug delivery systems hold promise for cancer treatment by enhancing the solubility and stability of anti-tumor drugs. Nonetheless, the challenges of inadequate targeting and limited biocompatibility persist. In recent years, cell membrane nano-biomimetic drug delivery systems have emerged as a focal point of research and development, due to their exceptional traits, including precise targeting, low toxicity, and good biocompatibility. This review outlines the categorization and advantages of cell membrane bionic nano-delivery systems, provides an introduction to preparation methods, and assesses their applications in cancer treatment, including chemotherapy, gene therapy, immunotherapy, photodynamic therapy, photothermal therapy, and combination therapy. Notably, the review delves into the challenges in the application of various cell membrane bionic nano-delivery systems and identifies opportunities for future advancement. Embracing cell membrane-coated biomimetic nanoparticles presents a novel and unparalleled avenue for personalized tumor therapy.

Photothermal and ferroptosis synergistic therapy for liver cancer using iron-doped polydopamine nanozymes

An innovative nanozyme, iron-doped polydopamine (Fe-PDA), which integrates iron ions into a PDA matrix, conferred peroxidase-mimetic activity and achieved a substantial photothermal conversion efficiency of 43.5 %. Fe-PDA mediated the catalysis of H2O2 to produce toxic hydroxyl radicals (•OH), thereby facilitating lipid peroxidation in tumour cells and inducing ferroptosis. Downregulation of solute carrier family 7 no. 11 (SLC7A11) and solute carrier family 3 no. 2 (SLC3A2) in System Xc- resulted in decreased intracellular glutathione (GSH) production and inactivation of the nuclear factor erythroid 2-related factor 2 (NRF2)-glutathione peroxidase 4 (GPX4) pathway, contributing to ferroptosis. Moreover, the application of photothermal therapy (PTT) enhanced the effectiveness of chemodynamic therapy (CDT), accelerating the Fenton reaction for targeted tumour eradication while sparing adjacent non-cancerous tissues. In vivo experiments revealed that Fe-PDA significantly hampered tumour progression in mice, emphasizing the potential of the dual-modality treatment combining CDT and PTT for future clinical oncology applications.

Facile construction of gold- and BODIPY-coordinated liposomal nanocomplexes for enhanced photothermal therapy of cancer

Photothermal therapy (PTT) has attracted extensive attention in cancer treatment because of its advantages of non-invasive and few side effects. Gold nanoparticles and boron-fluorine-dipyrrole (BODIPY) dye have been used as photothermal agents (PTAs), but they have problems such as easy aggregation, poor water solubility and low photothermal conversion efficiency. In this work, we used conventional liposomes for in situ generation of small gold nanoparticles and sequentially loading BODIPY to overcome the drawbacks of the two PTAs and simultaneously realize enhanced PTT. Gold- and BODIPY-coordinated liposomal nanocomplexes LAB with small gold nanoparticles adsorbed on the surface and BODIPY entrapped inside showed uniform size of about 100 nm with good stability. LAB demonstrated laser-responsive drug release property, good cellular uptake efficiency and tumor accumulation ability. After laser irradiation, LAB can exert enhanced PTT in cancer cell lines by reducing mitochondrial membrane potential and increase intracellular reactive oxygen species level to promote cell apoptosis. In tumor-bearing mice, LAB showed fantastic tumor inhibition effect with good biosafety. This work provides a convenient method to develop PTA combinations for enhanced PTT, which could lay the foundation for the green construction of new PTAs for PTT by employing clinically used formulations and PTAs.

Golgi Apparatus Targeted Graphene Oxide Nanocomposites for Synergistic Chemotherapy, Photothermal Therapy, and Photodynamic Therapy of Metastatic Breast Cancer

Golgi Apparatus Targeted Graphene Oxide Nanocomposites for Synergistic Chemotherapy, Photothermal Therapy, and Photodynamic Therapy of Metastatic Breast Cancer

Acceptor-donor-acceptor type organic photothermal agents with enhanced NIR absorption and photothermal conversion effect for cancer photothermal therapy

Numerous photothermal agents (PTAs) require high-intensity and long-duration laser excitation for photothermal therapy (PTT), resulting in light damage to healthy skin and tissue as well as limiting their biomedical applications. Integrating desirable near-infrared (NIR) absorption and high photothermal conversion efficiency (PCE) into a single small-molecule PTA is an important prerequisite for realizing efficient PTT, but is a serious challenge. Herein, through molecular engineering strategy, an acceptor-donor-acceptor (A-D-A) type PTA (ADA3) was readily developed for 808 nm laser-driving photothermal imaging and PTT of tumor. Theoretical calculations and experiment results show molecular engineering strategy is significant in regulating the structure and energy gap of PTAs, so as to effectively induce a narrow band gap for NIR absorption and further optimize photothermal properties. ADA3 possesses molar extinction coefficient of 3.1 × 104 M−1 cm−1 at 808 nm, followed being assembled into nanoparticles, ADA3-NPs show high PCE of 80.3%. In vivo experiments indicate that ADA3-NPs have excellent antitumor capability under one-time, low-intensity and short-duration (808 nm, 330 mW/cm2, 3 min) laser irradiation. Therefore, this work definitely exemplifies the enormous potential of molecular engineering strategy and provides an effective method for developing small-molecule PTAs.

A novel combined therapeutic strategy of Nano-EN-IR@Lip mediated photothermal therapy and stem cell inhibition for gastric cancer

Recurrence and metastasis of gastric cancer is a major therapeutic challenge for treatment. The presence of cancer stem cells (CSCs) is a major obstacle to the success of current cancer therapy, often leading to treatment resistance and tumor recurrence and metastasis. Therefore, it is important to develop effective strategies to eradicate CSCs. In this study, we developed a combined therapeutic strategy of photothermal therapy (PTT) and gastric cancer stem cells (GCSCs) inhibition by successfully synthesizing nanoliposomes loaded with IR780 (photosensitizer) and EN4 (c-Myc inhibitor). The nanocomposites are biocompatible and exhibit superior photoacoustic (PA) imaging properties. Under laser irradiation, IR780-mediated PTT effectively and rapidly killed tumor cells, while EN4 synergistically inhibited the self-renewal and stemness of GCSCs by suppressing the expression and activity of the pluripotent transcription factor c-Myc, preventing the tumor progression of gastric cancer. This Nano-EN-IR@Lip is expected to be a novel clinical nanomedicine for the integration of gastric cancer diagnosis, treatment and prevention.