External Laser Irradiation Research Articles

Chemiexcitation-Triggered Photosensitizer Activation for Photooxidation of Aβ1-42 Aggregates.

Oxidative degradation of the pathogenic amyloid-β-peptide (Aβ) aggregation is an effective and promising method to treat Alzheimer's disease under light irradiation. However, the limited penetration of external light sources into deep tissues has hindered the development of this treatment. Therefore, we have designed an unprecedented chemiluminescence-initiated photodynamic therapy system to replace external laser irradiation, primarily composed of d-glucose-based polyoxalate (G-poly(oxalate)), the novel photosensitizer (BD-Se-QM), and bis [2,4,5-trichloro-6-(pentoxy-carbonyl) phenyl] ester. BD-Se-QM possesses excellent singlet oxygen (1O2) generation efficiency and the ability to photooxidize Aβ1-42 aggregates under white light. G-poly(oxalate) not only helps the nanosystem to cross the blood-brain barrier but also has sufficient oxalate ester groups to significantly enhance the efficiency of chemiluminescence resonance energy transfer. The oxalate ester groups in BD-Se-QM/NPs can chemically react with H2O2 to produce high-energy intermediates that activate BD-Se-QM, which can generate 1O2 to inhibit Aβ1-42 aggregates and also promote microglial uptake of Aβ1-42, reducing the Aβ1-42-induced neurotoxicity. The chemically stimulated nanoplatform not only solves the drug delivery problem but also eliminates the need for external light sources. We anticipate that this chemically excited nanosystem could also be used for targeted delivery of other small molecule drugs.

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.

Electro-osmotic transport and thermal energy dynamics of tetra-hybrid nano fluid in complex peristaltic flows

BackgroundThis study explores the use of tetra-hybrid nanoparticles consisting of gold, silver, alumina, and titania nanocomposites dispersed in a non-Newtonian Casson fluid modelled as blood. The motivation lies in harnessing the synergistic optical, electrical, thermal, and physicochemical properties of the multimodal nanoscale assembly to advance electrokinetic pumping processes. ObjectivesThe study aims to computationally investigate the complex transport assisted by tailored gold, silver, alumina, and titania dioxide nanoparticles in the tetra-hybrid nanofluid, with potential applications in targeted drug delivery, hyperthermia cancer treatment, Lab-on-Chip devices, and miniaturized biosensors. MethodologyThe constructed streaming flow model examines the cumulative influence of viscous heating, Joule heating, conductive thermal, and external laser irradiation. Current simulations examine Casson flows with the integrated nanoparticles by modelling two- and three-dimensional conduits subject to transverse magnetohydrodynamics and localized laser irradiation. Key findingsThe solutions provide mathematical predictions and physical insights into the fully coupled velocity, temperature, concentration, and pressure gradient contours. Additional plots examining dimensionless analytes against pertinent profiles, combined with streamlined visualization, further elucidate the multifaceted transport and complex trapping patterns stemming from non-Newtonian rheology. Applications/implicationsThis multiscale examination reveals performance improvements realizable by leveraging biocompatible tetra-hybrid nanocomposites in electrokinetic flows vital for next-generation biomedical technologies.

A laser free self-luminous nanosystem for photodynamic therapy of cervical cancer cells

Photodynamic therapy is a tumor treatment strategy. However, most of the photodynamic therapies rely on laser irradiation triggering, which limits their application in deep tissues. This study designed a self-luminescent nano system, hybrid protein oxygen nanocarrier coated graphene quantum dots (GQDs@HPOC) and mesoporous silica nanoparticles coated Luminol (L@MSNs), which self-assembled into GQDs@HPOC/L@MSNs without laser irradiation. The system utilized the weak acidic environment of tumors to trigger the release of Luminol and the chemiluminescence was catalyzed by HPOC. Next CRET occurred between Luminol and GQDs, producing 1O2, which could generate photodynamic damage to cervical cancer cells without the need for external laser irradiation. The system achieved the peak uptake in primary cervical cancer cells in 3 h, and had good biosafety before self-assembly. The system could significantly kill cells at a concentration of 16 μg/ml. The system will be further applied in in vivo experiments to investigate its therapeutic ability, providing a new strategy for the clinical treatment of cervical cancer.

An Intelligent Laser-Free Photodynamic Therapy Based on Endogenous miRNA-Amplified CRET Nanoplatform.

Laser-free photodynamic therapy (PDT) is a promising noninvasive therapeutic modality for deep-seated tumor, yet is constrained by low efficiency due to the limited stimulation strategies. Herein, a novel miRNA-responsive laser-free PDT was developed through metal-organic frameworks (MOFs)-mediated chemiluminescence resonance energy transfer (CRET) nanoplatform. The photosensitizer chlorin e6 (Ce6)-loaded MOFs were functionalized with hairpin nucleic acids for sensitive responsiveness of tumor biomarker miRNA through catalytic hairpin assembly (CHA), which enabled the amplified assembly of horseradish peroxidase (HRP)-mimicking hemin/G-quadruplex DNAzyme on MOFs. Simultaneously, the on-MOF assembled DNAzymes efficiently catalyzed chemiluminescence reaction to stimulate adjacent Ce6 in the presence of luminol and H2 O2 , thus allowing the CRET-mediated Ce6 luminescence and reactive oxygen species (ROS) generation for self-illuminating PDT. The CRET nanoplatform achieved significant malignant cell apoptosis and tumor inhibition effects without external laser irradiation. It is envisioned that the miRNA-amplified CRET nanoplatform might be a selective and highly efficient antitumor nanomedicine for precise theranostic.

A Smart Benzothiazole-Based Conjugated Polymer Nanoplatform with Multistimuli Response for Enhanced Synergistic Chemo-Photothermal Cancer Therapy

The combination of chemotherapy and phototherapy has received tremendous attention in multimodal cancer therapy. However, satisfactory therapeutic outcomes of chemo-photothermal therapy (chemo-PTT) still remain challenging. Herein, a biocompatible smart nanoplatform based on benzothiazole-linked conjugated polymer nanoparticles (CPNs) is rationally designed, for effectively loading doxorubicin (DOX) and Mo-based polyoxometalate (POM) through both dynamic chemical bond and intermolecular interactions, with an expectation to obtain new anticancer drugs with multiple stimulated responses to the tumor microenvironment (TME) and external laser irradiation. Controlled drug release of DOX from the obtained nanoformulation (CPNs-DOX-PEG-cRGD-BSA@POM) triggered by both endogenous stimulations (GSH and low pH) and exogenous laser irradiation has been well demonstrated by pharmacodynamics investigations. More intriguingly, incorporating POM into the nanoplatform not only enables the nanomedicine to achieve mild hyperthermia but also makes it exhibit self-assembly behavior in acidic TME, producing enhanced tumor retention. Benefiting from the versatile functions, the prepared CPNs-DOX-PEG-cRGD-BSA@POM exhibited excellent tumor targeting and therapeutic effects in murine xenografted models, showing great potential in practical cancer therapy.

Anti‐PD‐L1 DNAzyme Loaded Photothermal Mn2+/Fe3+ Hybrid Metal‐Phenolic Networks for Cyclically Amplified Tumor Ferroptosis‐Immunotherapy (Adv. Healthcare Mater. 8/2022)

Tumor Therapy In article number 2102315 by Wenhu Zhou and co-workers, a metal-phenolic network (MPN) nanoplatform with all-active components is constructed via coordination between tannic acid (TA) and metal ion complex of Fe3+/Mn2+, through which a PD-L1 inhibiting DNAzyme (DZ) is loaded. With external laser irradiation, PTT is initiated to synergize with ferroptosis for enhanced ICD, and the combination of DZ-mediated PD-L1 suppression results in a cyclically amplified tumor ferroptosis-immunotherapy.

SnSe-Coated Microfiber Resonator for All-Optical Modulation.

In this study, a tin monoselenide (SnSe)-based all-optical modulator is firstly demonstrated with high tuning efficiency, broad bandwidth, and fast response time. The SnSe nanoplates are deposited in the microfiber knot resonator (MKR) on MgF2 substrate and change its transmission spectra by the external laser irradiation. The SnSe nanoplates and the microfiber are fabricated using the liquid-phase exfoliation method and the heat-flame taper-drawing method, respectively. Due to the strong absorption and enhanced light–matter interaction of the SnSe nanoplates, the largest transmitted power tunability is approximately 0.29 dB/mW with the response time of less than 2 ms. The broad tuning bandwidth is confirmed by four external pump lights ranging from ultraviolet to near-infrared. The proposed SnSe-coated microfiber resonator holds promising potential for wide application in the fields of all-optical tuning and fiber sensors.

Tumor Microenvironment Activated Chemodynamic–Photodynamic Therapy by Multistage Self‐Assembly Engineered Protein Nanomedicine

AbstractWhile cytotoxic reactive oxygen species (ROS) play an important role in fighting cancer, developing an activable ROS‐generating system to achieve highly specific cancer therapy with minimum side effects to normal tissues remains challenging. This work reports the development of a tumor microenvironment‐activable ROS‐generating system via multistage self‐assembly engineered protein‐based nanomedicine containing cascade enzymes and photosensitizers. The multistage self‐assembly‐induced aggregation not only prevents the premature exposure of cascade enzymes to produce toxic by‐products in noncancerous sites, but also quenches the photosensitizers to diminish skin phototoxicity, contributing to effective self‐protection of normal tissues. Once triggered by the intratumoral reduction microenvironment, the aggregation effect is unlocked to expose cascade enzymes and recover the photosensitivity, which can decompose intratumor glucose for hydroxyl radical generation and respond to external laser irradiation for singlet oxygen production respectively, realizing tumor‐specific chemodynamic–photodynamic combinational therapy. This work demonstrates a protein‐based multistage self‐assembly approach for ROS‐mediated cancer‐specific therapy with effective self‐protection, offering a powerful strategy for nanomedicine design and more precise cancer therapy.

Anti-PD-L1 DNAzyme Loaded Photothermal Mn2+ /Fe3+ Hybrid Metal-Phenolic Networks for Cyclically Amplified Tumor Ferroptosis-Immunotherapy.

Ferroptosis can activate immune response via inducing tumor cells immunogenic cell death (ICD), and antitumor immunity in turn boosts the efficacy of ferroptosis by excreting interferon gamma (IFN-γ), which shows a promising combo for synergistically amplified tumor treatment. However, their combination is strictly limited by the complexity of tumor microenvironment, including poor ferroptosis response and immunosuppressive factors in tumor. Herein, a metal-phenolic networks (MPNs) nanoplatform with all-active components is constructed to favor the ferroptosis-immunotherapy cyclical synergism. The photothermal MPNs are assembled via coordination between tannic acid (TA) and metal-ion complex of Fe3+ /Mn2+ , through which a PD-L1 inhibiting DNAzyme (DZ) is loaded to regulate the immunosuppressive PD-1/PD-L1 pathway. After intracellular delivery, each component of MPNs exerts their respective functions: Fe2+ is in situ generated from Fe3+ by TA reduction to trigger ferroptosis, while DZ is activated by Mn2+ to effectively silence PD-L1. With external laser irradiation, photothermal therapy is initiated to synergize with ferroptosis for enhanced ICD, which induces strong antitumor immunes. Combined with DZ-mediated PD-L1 suppression, a cyclically amplified tumor ferroptosis-immunotherapy is achieved, resulting in obliteration of both primary and distant tumor. This work provides a smart, simple, yet robust nanomedicine-based combination for self-amplified tumor treatment.

Visible light photostriction in Kagome staircase zinc ortho-vanadate

Ferroelectric materials have been widely explored for photostrictive action, but their high performance being limited to ultra violet light demands to look for efficient visible light photostrictive materials. Transition metal vanadates, exhibiting the Kagome structural features besides being active in visible light, are the interesting materials for the photostriction study. Here, we investigate the photostriction of the non-magnetic member zinc ortho-vanadate Zn3(VO4)2 or Zn3V2O8. Corresponding to the photostriction response of ∼10−3 under a 405 nm laser (response time, τ = 5.7 s) and ∼10−4 (τ = 5.8 s) under a 665 nm laser, it exhibits a large photostriction efficiency of ∼10−11 and ∼10−12 m3/W, respectively. Thermal expansion investigation indicates that the non-thermal strain dominants the photostriction of Zn3V2O8 ceramics. The peak shift in x-ray diffraction (XRD) pattern as well as in Raman spectra under external laser irradiance revealing, increased anisotropic distortions with increasing stretching and vibrations in the bonds of ZnO6 octahedrons and VO4 tetrahedrons, is proposed as the underlying mechanism of the photostriction response in Zn3V2O8. The good visible light photostriction, rapid response time, and stability functionalities make it a potential candidate for future generation optoelectronics, such as light driven micro-actuators, robots, relays, and other optomechanical devices.

The Therapeutic Effect of Second Near-Infrared Absorbing Gold Nanorods on Metastatic Lymph Nodes via Lymphatic Delivery System.

Photothermal therapy has been established recently as a non-invasive treatment protocol for cancer metastatic lymph nodes. Although this treatment approach shows efficient tumour ablation towards lymph node metastasis, the monitoring and reporting of treatment progress using the lymphatic delivery channel still need to be explored. Herein, we investigated the anti-tumour effect of pegylated gold nanorods with a high aspect ratio (PAuNRs) delivered via the lymphatic route in a mouse model. In this study, breast carcinoma (FM3A-Luc) cells were inoculated in the subiliac lymph node (SiLN) to induce metastasis in the proper axillary lymph node (PALN). The treatment was initiated by injecting the PAuNRs into the accessory axillary lymph node (AALN) after tumour metastasis was confirmed in the PALN followed by external NIR laser irradiation under a temperature-controlled cooling system. The anti-tumour impact of the treatment was evaluated using an in vivo bioluminescence imaging system (IVIS). The results showed a time-dependent reduction in tumour activity with significant treatment response. Tumour growth was inhibited in all mice treated with PAuNRs under laser irradiation; results were statistically significant (** p < 0.01) even after treatment was concluded on day 3. We believe that this non-invasive technique would provide more information on the dynamics of tumour therapy using the lymphatically administered route in preclinical studies.

Optical and thermal fields induced in the bone marrow by external laser irradiation

In regenerative medicine, the problem of growing mesenchymal stem cells from the bone marrow often arises. In such cases is important that the number of initial cells was large enough and their proliferative activity was high. We believe that this problem can be solved by short-term heating of local areas of the bone marrow in vivo with laser radiation. In this regard, it is of interest to study the optical and temperature fields induced inside the tubular bone under external laser irradiation. In this work, we obtained experimental data on the spatial distribution of temperature in the bone marrow of the rat femur in vitro under external exposure to laser radiation with wavelengths of 970 and 1940nm. Radiation delivery was carried out using an optical fiber which tip contacted the surface of the femur bone. A thin thermocouple was used to measure the temperature in a local area of the bone marrow. By moving the optical fiber tip discretely along the longitudinal axis of the bone, and the thermocouple in the perpendicular direction, the spatial temperature distributions in dynamics were measured. Similarly, the spatial distributions of the laser radiation intensity were measured by replacing thermocouple with optical fiber probe. A thermal camera was used to control the temperature of the bone surface near the tip of the fiber. It was shown that the marrow could be heated from the outside by about 5-10°C during 10s without significant overheating of the bone tissue. The data obtained make it possible to estimate the volume of the bone marrow heated by the laser to a predetermined temperature and to make a reasonable choice of laser exposure modes to stimulate the proliferative activity of bone marrow mesenchymal stem cells in vivo.

Infrared Responsive Choline Phosphate Lipids for Synergistic Cancer Therapy.

Choline phosphate lipids have been designed and developed as new-generation zwitterionic nanocarriers with excellent biocompatibility and bioorthogonality to provide a more programmable performance for cancer therapy. However, there is a lack of spatiotemporal and reversible control for drug release at target tumor cells, which can lead to severe adverse effects to normal tissue and discounted treatment outcome. Here, light-inducible Lip-cRGDfk/ICG/Dox liposomes were developed for synergistic cancer therapy. ICG can effectively convert light energy into selective heating in a local environment upon laser irradiation, thus inducing thermal ablation of tumor cells, and further reversibly trigger the spatiotemporal release of anticancer drugs (Dox) at tumor cells due to the conformation transformation of CP lipids to synergistically kill tumor cells. That Lip-cRGDfk/ICG/Dox exhibited a significant improvement for breast cancer therapy in vitro and in vivo is also demonstrated, thus it can serve as an efficient platform to noninvasively and spatiotemporally control the activation of cytotoxicity at tumor cells for precision cancer therapy.

On thermal regime of nanoparticles in synthesis flame

Flame Synthesis conditions significantly affect nanoparticles properties. Understanding thermal regime in flames can be very useful for tuning nanoparticles with specific properties. In this work, information on thermal status is obtained through the analysis of light emission from nanoparticles during synthesis and under an external laser irradiation. We focus on the dependence of the particle temperature on laser fluence as reported in our previous work. We discuss temperature plateau observed in the low laser fluence regime as attributed to non-isothermality, that means the local coexistence of partially solidified particles at melting point and much hotter particles in a flame spray.

О возможности применения фторидных неодим-активированных кристаллов в качестве светоуправляемого затворв для излучения ArF-лазера (193 nm)

Сообщено об оптических свойствах кристаллов фторидов KY3F10:Nd3+, Na3Y6F22:Nd3+, SrF2:Nd3+ и CaF2:Nd3+ в УФ и ВУФ областях спектра. Спектры поглощения из основного (4I9/2) и из возбужденного (4F3/2) состояний зарегистрированы в диапазоне длин волн от 190 до 240 nm. Спектры поглощения из возбужденного состояния показывают существенное приращение коэффициентов поглощения исследованных образцов в области длин волн 193 nm при накачке состояния 4F3/2 ионов Nd3+ ИК излучением. Полученные результаты демонстрируют возможность применения этих кристаллов в качестве оптических затворов для УФ и ВУФ диапазона, управляемых внешним лазерным ИК излучением, например для излучения эксимерного ArF-лазера с длиной волны 193 nm, которое начало применяться в фотолитографии. Ключевые слова: фторидный кристалл, ионы неодима, ВУФ, УФ, спектр поглощения, поглощение из возбужденного состояния, оптический затвор, 193 nm, эксимерный ArF-лазер.

Bi2O2Se for broadband terahertz wave switching.

Many modern terahertz systems require dynamic manipulation of a terahertz wave. We proposed a terahertz wave switch based on a Bi2O2Se/Si structure. The transmittance and conductivity characteristics of the Bi2O2Se in a terahertz region have been measured by terahertz time-domain spectroscopy and analyzed using the Drude model. An ON-OFF switching speed as fast as 2 MHz and an extinction ratio as high as 17.7 dB was achieved at an external laser irradiance of 1.3W/cm2. The switching characteristics of the device can be explained by the accumulation of carriers at the interface that induces terahertz wave intense absorption. Our approach can effectively be used to realize a wide range of dynamically tunable terahertz functional devices. This makes its use viable for a range of communication, imaging, and sensing applications.

Tumor microenvironment triple-responsive nanoparticles enable enhanced tumor penetration and synergetic chemo-photodynamic therapy

A novel combined chemo/photodynamic therapy has been developed to use pH/ROS/MMP-2 triple-responsive drug nanocarriers for treating solid tumor with an extraordinarily high efficiency. The designed poly(ethylene glycol)-peptide-poly(ω-pentadecalactone-co-N-methyldiethyleneamine-co-3,3′-thiodipropionate) (PEG-M-PPMT) nanoparticles (NPs) encapsulating anticancer drug sorafenib (SRF) and photosensitizer chlorin e6 (Ce6) are stable in serum-containing aqueous media and can effectively accumulate in tumor as a result of the EPR effect after intravenous administration in vivo. In the presence of MMP-2 overexpressed in extracellular tumor matrix, the PEG-M-PPMT NPs can partially shed PEG corona to form smaller particles and penetrate deep into tumor tissue. After uptake by tumor cells, the acidic endosomal pH and high intracellular ROS level would trigger substantial swelling of the NPs to accelerate the drug release for rapid killing of the cancer cells. In the current combined chemo/photodynamic therapy, the intracellular ROS generation in tumor is amplified by photosensitizer Ce6 activated with external laser irradiation. As the result, the highly elevated intracellular ROS concentration can both directly induce apoptosis of ROS-stressed tumor cells and magnify acceleration of the drug release from the ROS-responsive PEG-M-PPMT NPs to gain extraordinary therapeutic efficacy. In particular, after the chemo-photodynamic therapeutic treatment with SRF/Ce6-loaded PEG-M-PPMT nanoparticles, all human lung tumors (A549) xenografted in nude mice shrank substantially with approximately 29% of the tumors being completely eradicated. Additionally, SRF/Ce6-loaded PEG-M-PPMT NPs show negligible in vivo toxicity toward major organs such as heart, liver, spleen, lung and kidney. These results demonstrate great potential of the combined chemo/photodynamic therapy based on the stimuli-responsive PEG-M-PPMT nanoparticles for efficient tumor treatment.

Stepwise-activatable hypoxia triggered nanocarrier-based photodynamic therapy for effective synergistic bioreductive chemotherapy

Tumor cell populations are highly heterogeneous, which limit the homogeneous distribution and optimal delivery of nanomedicines, thereby inducing insufficient therapeutic benefits. We develop tumor microenvironment activatable and external stimuli-responsive drug delivery system (TAT+AzoNPs), which can improve photodynamic therapy (PDT) induced bioreductive chemotherapy in different tumor cells both proximal and distal to vessels. The TAT peptide on the surface of TAT+AzoNPs can both facilitate the cell uptake and the penetration of TAT+AzoNPs, owing to its responsiveness to tumor stimuli pH. TAT+AzoNPs can keep the cargoes (photosensitizer chlorine e6 (Ce6) and hypoxia activatable prodrug tirapazamine (TPZ)) and highly accumulate within tumor cells proximity and distal to vessels. The Azo-benzene bonds as the linkers between amphiphilic polymers remain stable under normoxia, but quite break at hypoxic conditions. Upon external laser irradiation, the intratumoral fate of TAT+AzoNPs involved two processes: 1) TAT+AzoNPs achieve efficient PDT on tumor cells proximal to vessel, since sufficient O2 supply; and 2) PDT-induced more hypoxia can trigger TPZ release by breakage of Azo-benzene bond as well as accelerate the activation of TPZ for improvingcombination therapy efficacy in tumor cells distal to vessel. This study gives a direction for the development of stepwise-activatable hypoxia triggered nanosystem for PDT-induced bioreductive chemotherapy for tumor cells in different distances to vessels.

A multifunctional nanoplatform based on MoS2-nanosheets for targeted drug delivery and chemo-photothermal therapy

Synergistic tumor treatment has recently attracted more and more attention due to its remarkable therapeutic effect. Herein, a multifunctional drug delivery system based on hyaluronic acid (HA) targeted dual stimulation responsive MoS2 nanosheets (HA-PEI-LA-MoS2-PEG, HPMP) for active interaction with CD44 receptor positive MCF-7 cells is reported. Melanin (Mel), a new type of photothermal agent and doxorubicin (DOX) are both loaded onto the HPMP nanocomposite and can be released by mild acid or hyperthermia. The prepared HPMP nanocomposite has a uniform hydrodynamic diameter (104 nm), a high drug loading (944.3 mg.g−1 HPMP), a remarkable photothermal effect (photothermal conversion efficiency: 55.3%) and excellent biocompatibility. The DOX release from HPMP@(DOX/Mel) can be precisely controlled by the dual stimuli of utilizing the acidic environment in the tumor cells and external laser irradiation. Meanwhile, loading of Mel onto the surface can enhance the photothermal effect of the MoS2 nanosheets. In vitro experiments showed that the HPMP@(DOX/Mel) nanoplatform could efficiently deliver DOX into MCF-7 cells and demonstrated enhanced cytotoxicity compared to that of the non-targeted nanoplatform. In vivo experiments in a breast cancer model of nude mice further confirmed that the HPMP@(DOX/Mel) significantly inhibited tumor growth under near infrared (NIR) laser irradiation, which is superior to any single therapy. In summary, this flexible nanoplatform, based on multi-faceted loaded MoS2 nanosheets, exhibits considerable potential for efficient pH/NIR-responsive targeted drug delivery and chemo-photothermal synergistic tumor therapy.