Natural MOF-Like Photocatalytic Nanozymes Alleviate Tumor Pressure for Enhanced Nanodrug Penetration.

In oncological nanomedicine, overcoming the dual-phase high interstitial pressure in the tumor microenvironment is pivotal for enhancing the penetration and efficacy of nanotherapeutics. The elevated tumor interstitial solid pressure (TISP) is largely attributed to the overaccumulation of collagen in the extracellular matrix, while the increased tumor interstitial fluid pressure (TIFP) stems from the accumulation of fluid due to the aberrant vascular architecture. In this context, metal-organic frameworks (MOFs) with catalytic efficiency have shown potential in degrading tumor interstitial components, thereby reducing interstitial pressure. However, the potential biotoxicity of the organic components of MOFs limits their clinical translation. To circumvent this, a MOF-like photocatalytic nanozyme, RPC@M, using naturally derived cobalt phytate (CoPA) and resveratrol (Res) is developed. This nanozyme not only facilitates the decomposition of water in the tumor interstitium under photoactivation to reduce TIFP, but also generates an abundance of reactive oxygen species through its peroxidase-like activity to exert cytotoxic effects on tumor cells. Moreover, Res contributes to the reduction of collagen deposition, thereby lowering TISP. The concurrent diminution of both TISP and TIFP by RPC@M leads to enhanced tumor penetration and potent antitumor activity, presenting an innovative approach in constructing tumor therapeutic nanozymes from natural products.

Achieving deep intratumoral penetration and multimodal combined therapy for tumor through algal photosynthesis.

BACKGROUND: Elevated interstitial fluid pressure within tumors, resulting from impaired lymphatic drainage, constitutes a critical barrier to effective drug penetration and therapeutic outcomes. RESULTS: In this study, based on the photosynthetic characteristics of algae, an active drug carrier (CP@ICG) derived from Chlorella pyrenoidosa (CP) was designed and constructed. Leveraging the hypoxia tropism and phototropism exhibited by CP, we achieved targeted transport of the carrier to tumor sites. Additionally, dual near-infrared (NIR) irradiation at the tumor site facilitated photosynthesis in CP, enabling the breakdown of excessive intratumoral interstitial fluid by generating oxygen from water decomposition. This process effectively reduced the interstitial pressure, thereby promoting enhanced perfusion of blood into the tumor, significantly improving deep-seated penetration of chemotherapeutic agents, and alleviating tumor hypoxia. CONCLUSIONS: CP@ICG demonstrated a combined effect of photothermal/photodynamic/starvation therapy, exhibiting excellent in vitro/in vivo anti-tumor efficacy and favorable biocompatibility. This work provides a scientific foundation for the application of microbial-enhanced intratumoral drug delivery and tumor therapy.

A universal nanoreactor triggering butterfly effect for encouraging Fenton/Fenton-like reactions and chemodynamic therapy.

Fenton/Fenton-like reaction induced chemical dynamic therapy (CDT) has been widely recognized in tumor therapy. Due to the low efficiency of conversion from high-valent metal ions (M(n+1)+) to low-valent ions (Mn+) in the Fenton/Fenton-like catalytic process, enhancing the conversion efficiency safely and effectively would create a great opportunity for the clinical application of CDT. In the study, a universal nanoreactor (NR) consisting of liposome (Lip), tumor cell membrane (CM), and bis(2,4,5-trichloro-6-carboxyphenyl) oxalate (CPPO) is developed to tackle this challenge. The CPPO was first discovered to decompose under weak acidity and H2O2 conditions to generate carboxylic acids (R'COOH) and alcohols (R'OH) with reducibility, which will reduce M(n+1)+ to Mn+ and magnify the effect of CDT. Furthermore, glucose oxidase (GOx) was introduced to decompose glucose in tumor and generate H2O2 and glucose acid, which promote the degradation of CPPO, further strengthening the efficiency of CDT, leading to a butterfly effect. This demonstrated that the butterfly effect triggered by NR and GOx encourages Fenton/Fenton-like reactions of Fe3O4 and MoS2, thereby enhancing the tumor inhibition effect. The strategy of combining GOx and CPPO to strengthen the Fenton/Fenton-like reaction is a universal strategy, which provides a new and interesting perspective for CPPO in the application of CDT, reflecting the exquisite integration of Fenton chemistry and catalytic medicine.

Nanomedicine alleviates doxorubicin-induced cardiotoxicity and enhances chemotherapy synergistic chemodynamic therapy.

Doxorubicin (DOX) is widely used in clinic as a broad-spectrum chemotherapy drug, which can enhance the efficacy of chemodynamic therapy (CDT) by interfering tumor-related metabolize to increase H2O2 content. However, DOX can induce serious cardiomyopathy (DIC) due to its oxidative stress in cardiomyocytes. Eliminating oxidative stress would create a significant opportunity for the clinical application of DOX combined with CDT. To address this issue, we introduced sodium ascorbate (AscNa), the main reason is that AscNa can be catalyzed to produce H2O2 by the abundant Fe3+ in the tumor site, thereby enhancing CDT. While the content of Fe3+ in heart tissue is relatively low, so the oxidation of AscNa had tumor specificity. Meanwhile, due to its inherent reducing properties, AscNa could also eliminate the oxidative stress generated by DOX, preventing cardiotoxicity. Due to the differences between myocardial tissue and tumor microenvironment, a novel nanomedicine was designed. MoS2 was employed as a carrier and CDT catalyst, loaded with DOX and AscNa, coating with homologous tumor cell membrane to construct an acid-responsive nanomedicine MoS2-DOX/AscNa@M (MDA@M). In tumor cells, AscNa enhances the synergistic therapy of DOX and MoS2. In cardiomyocytes, AscNa could effectively reduce the cardiomyopathy induced by DOX. Overall, this study enhanced the clinical potential of chemotherapy synergistic CDT.

Flexocatalytic Reduction of Tumor Interstitial Fluid/Solid Pressure for Efficient Nanodrug Penetration.

The practical efficacy of nanomedicines for treating solid tumors is frequently low, predominantly due to the elevated interstitial pressure within such tumors that obstructs the penetration of nanomedicines. This increased interstitial pressure originates from both liquid and solid stresses related to an undeveloped vascular network and excessive fibroblast proliferation. To specifically resolve the penetration issues of nanomedicines for tumor treatment, this study introduces a holistic "dual-faceted" approach. A treatment platform predicated on the WS2/Pt Schottky heterojunction was adopted, and flexocatalysis technology was used to disintegrate tumor interstitial fluids, thus producing oxygen and reactive oxygen species and effectively mitigating the interstitial fluid pressure. The chemotherapeutic agent curcumin was incorporated to further suppress the activity of cancer-associated fibroblasts, minimize collagen deposition in the extracellular matrix, and alleviate solid stress. Nanomedicines achieve homologous targeting by enveloping the tumor cell membrane. It was found that this multidimensional strategy not only alleviated the high-pressure milieu of the tumor interstitium─which enhanced the efficiency of nanomedicine delivery─but also triggered tumor cell apoptosis via the generated reactive oxygen species and modulated the tumor microenvironment. This, in turn, amplified immune responses, substantially optimizing the therapeutic impacts of nanomedicines.

Piezoelectric Catalysis Induces Tumor Cell Senescence to Boost Chemo-Immunotherapy.

Cellular senescence, a vulnerable state of growth arrest, has been regarded as a potential strategy to weaken the resistance of tumor cells, leading to dramatic improvements in treatment efficacy. However, a selective and efficient strategy for inducing local tumor cellular senescence has not yet been reported. Herein, piezoelectric catalysis is utilized to reduce intracellular NAD+ to NADH for local tumor cell senescence for the first time. In detail, a biocompatible nanomedicine (BTO/Rh-D@M) is constructed by wrapping the piezoelectric BaTiO3/(Cp*RhCl2)2 (BTO/Rh) and doxorubicin (DOX) in the homologous cytomembrane with tumor target. After tumors are stimulated by ultrasound, negative and positive charges are generated on the BTO/Rh by piezoelectric catalysis, which reduce the intracellular NAD+ to NADH for cellular senescence and oxidize H2O to reactive oxygen species (ROS) for mitochondrial damage. Thus, the therapeutic efficacy of tumor immunogenic cell death-induced chemo-immunotherapy is boosted by combining cellular senescence, DOX, and ROS. The results indicate that 23.9% of the piezoelectric catalysis-treated tumor cells senesced, and solid tumors in mice disappeared completely after therapy. Collectively, this study highlights a novel strategy to realize cellular senescence utilizing piezoelectric catalysis and the significance of inducing tumor cellular senescence to improve therapeutic efficacy.

Cascaded Antitumor Therapy Excited by Dual Nanozymes Based on Energy Restriction and Photocatalysis.

In nanocatalytic medicine, drugs can be transformed into toxic components through highly selective and highly specific catalytic reactions in the tumor microenvironment, avoiding toxic side effects on normal tissues. Due to the coexistence of Ce3+ and Ce4+, CeO2 is endowed with dual nanozyme activities. Herein, CeO2 nanoparticles served as templates to construct a biomimetic nanodrug delivery system (C/CeO2@M) by electrostatic adsorption of carbon quantum dots (CQDs) and coating a homologous tumor cytomembrane. After homologous targeting to tumors, the CQDs emitted 350-600 nm light under 660 nm laser irradiation by upconversion luminescence, which caused a CeO2-mediated photocatalytic reaction to generate reactive oxygen species. The catalase-like activity of CeO2-enabled converting excess H2O2 to O2, which not only alleviated tumor hypoxia and promoted intratumor drug delivery but also provided substrates for subsequent catalytic reactions. Meanwhile, the phosphatase activity of CeO2 could consume adenosine triphosphate (ATP) to block the energy supply for tumor cells, thus limiting cell proliferation and metastasis. The strategy of energy restriction and photocatalysis of dual nanozyme stimulation offers great potentials in enhancing drug penetration and eradicating solid tumors.

Decrease in Tumor Interstitial Pressure for Enhanced Drug Intratumoral Delivery and Synergistic Tumor Therapy.

Currently, one of the main reasons for the ineffectiveness of tumor treatment is that the abnormally high tumor interstitial pressure (TIP) hinders the delivery of drugs to the tumor center and promotes intratumoral cell survival and metastasis. Herein, we designed a "nanomotor" by in situ growth of Ag2S nanoparticles on the surface of ultrathin WS2 to fabricate Z-scheme photocatalytic drug AWS@M, which could rapidly enter tumors by splitting water in interstitial liquid to reduce TIP, along with O2 generation. Moreover, the O2 would be further converted to reactive oxygen species (ROS), accompanied by increased local temperature of tumors, and the combination of ROS with thermotherapy could eliminate the deep tumor cells. Therefore, the "nanomotor'' could effectively reduce the TIP levels of cervical cancer and pancreatic cancer (degradation rates of 40.2% and 36.1%, respectively) under 660 nm laser irradiation, further enhance intratumor drug delivery, and inhibit tumor growth (inhibition ratio 95.83% and 87.61%, respectively), and the related mechanism in vivo was explored. This work achieves efficiently photocatalytic water-splitting in tumor interstitial fluid to reduce TIP by the nanomotor, which addresses the bottleneck problem of blocking of intratumor drug delivery, and provides a general strategy for effectively inhibiting tumor growth.

Dual-activity nanozyme to initiate tandem catalysis for doubly enhancing ATP-depletion anti-tumor therapy.

Nanozymes can regulate metabolism to achieve precise anti-tumor therapy. However, the application of nanozymes with single catalytic properties is limited by complex tumor microenvironment (TME). Herein, we report a rarely discovered nanozyme ruthenium (Ru), which has double catalytic activity of glucose-oxidase-like (GOx-like) activity and peroxidase-like (POD-like) activity. Importantly, the GOx-like activity of Ru was proposed for the first time, which can catalyze glucose and O2 to product H2O2. And then, Ru nanozyme can connect the tandem catalysis to enhance various tumor therapy. Firstly, the atovaquone (ATO) and Ru NPs were covered with a hybrid membrane of tumor cells and liposomes to obtain Ru@ATO-Lip/M with homologous targeting. Due to the enhanced permeability and retention (EPR) effect and the tumor targeting, the Ru@ATO-Lip/M NPs could be efficiently delivered to tumor and taken up by tumor cells. Subsequently, the acidic environment of tumor activated Ru to catalyze H2O2 producing OH (Fenton-like reaction). Meanwhile, newly discovered ability of Ru catalyzed glucose and O2 to produce gluconic acid and H2O2, which provided sufficient substrates (H2O2) for continuously generating more OH. Therefore, Ru nanozyme aggravated the starvation and chemodynamic therapy (CDT). Further, ATO improved the hypoxia of the tumor microenvironment, achieving steadily synergistic anti-tumor effect. This study verified the glucose oxidase-like properties of Ru NPs for the first time, and the strategy enhanced the synergistic anti-tumor effects by CDT and starvation therapy, which provided a basis for further exploration of Ru nanozyme activity and application on antitumor.

A dual-responsive "Yin-Yang" photothermal delivery system to accelerate Parthenolide anti-tumor efficacy.

Parthenolide (PTL), a germacrane sesquiterpene lactone extracted from the "Yin" Chinese traditional herb feverfew, has gained interest due to its lethal effects on tumor cells and its pharmacological effects within traditional Chinese medicine theory. To overcome low, non-targeted accumulation and uncontrolled release of PTL administration, a dual-responsive PTL-liposomes@chitosan@gold nanoshells (PTL-Lips@CS@GNS) system was fabricated. Hyperthermia generated under light irradiation in the near-infrared region via local surface plasmon resonance of gold nanoshells induced photothermal therapy, which also stimulated PTL release due to the liposomes gel-to-liquid crystalline phase transition. Additionally, PTL-Lips@CS@GNS exhibited a pH-responsive release in the acidic tumor microenvironment. Collectively, this study provides a realistic strategy for an effective combination of traditional Chinese medicine and current nanotechnology for tumor therapy.

Diagnostic and therapeutic nanoenzymes for enhanced chemotherapy and photodynamic therapy.

Nanozymes, as a kind of artificial mimic enzymes, have superior catalytic capacity and stability. As lack of O2 in tumor cells can cause resistance to drugs, we designed drug delivery liposomes (MnO2-PTX/Ce6@lips) loaded with catalase-like nanozymes of manganese dioxide nanoparticles (MnO2 NPs), paclitaxel (PTX) and chlorin e6 (Ce6) to consume tumor's native H2O2 and produce O2. Based on the catalysis of MnO2 NPs, a large amount of oxygen was produced by MnO2-PTX/Ce6@lips to burst the liposomes and achieve a responsive release of the loaded drug (paclitaxel), and the released O2 relieved the chemoresistance of tumor cells and provided raw materials for photodynamic therapy. Subsequently, MnO2 NPs were decomposed into Mn2+ in an acidic tumor environment to be used as contrast agents for magnetic resonance imaging. The MnO2-PTX/Ce6@lips enhanced the efficacy of chemotherapy and photodynamic therapy (PDT) in bearing-tumor mice, even achieving complete cure. These results indicated the great potential of MnO2-PTX/Ce6@lips for the modulation of the TME and the enhancement of chemotherapy and PDT along with MRI tracing in the treatment of tumors.

Pyroelectric Catalysis-Based "Nano-Lymphatic" Reduces Tumor Interstitial Pressure for Enhanced Penetration and Hydrodynamic Therapy.

Because of the deficiency of lymphatic reflux in the tumor, the retention of tumor interstitial fluid causes aggravation of the tumor interstitial pressure (TIP), which leads to unsatisfactory tumor penetration of nanomedicine. It is the main inducement of tumor recurrence and metastasis. Herein, we design a pyroelectric catalysis-based "Nano-lymphatic" to decrease the TIP for enhanced tumor penetration and treatments. It realizes photothermal therapy and decomposition of tumor interstitial fluid under NIR-II laser irradiation after reaching the tumor, which reduces the TIP for enhanced tumor penetration. Simultaneously, reactive oxygen species generated during the pyroelectric catalysis can further damage deep tumor stem cells. The results indicate that the "Nano-lymphatic" relieves 52% of TIP, leading to enhanced tumor penetration, which effectively inhibits the tumor proliferation (93.75%) and recurrence. Our finding presents a rational strategy to reduce TIP by pyroelectric catalysis for enhanced tumor penetration and improved treatments, which is of great significance for drug delivery.

A magnetically responsive drug-loaded nanocatalyst with cobalt-involved redox for the enhancement of tumor ferrotherapy.

Herein, cobalt-involved redox in a magnetically responsive drug-loaded nanocatalyst (PTX/Co-Lips@Fe3O4) was used to convert Fe(iii) to Fe(ii) for enhancing tumor ferrotherapy for the first time. Moreover, this work highlighted an "all in one" strategy: (1) targeting, chemotherapy, and ferrotherapy in one nanomedicine, and (2) a decrease in GSH quantity, increase in the quantity of efficient catalytic ions, and use of a magnetic field, all in one tumor ferrotherapy enhancement approach.

Nano magnetic liposomes-encapsulated parthenolide and glucose oxidase for ultra-efficient synergistic antitumor therapy.

Multifunctional nanoplatforms yield extremely high synergistic therapeutic effects on the basis of low biological toxicity. Based on the unique tumor microenvironment (TME), a liposomes (Lips)-based multifunctional antitumor drug delivery system known as GOD-PTL-Lips@MNPs was synthesized for chemotherapy, chemodynamic therapy (CDT), starvation therapy, and magnetic targeting synergistic therapy. Evidence has suggested that parthenolide (PTL) can induce apoptosis and consume excessive glutathione (GSH), thereby increasing the efficacy of chemodynamic therapy. On the other hand, glucose oxidase (GOD) can consume intratumoral glucose, lower pH and increase the level of H2O2 in the tumor tissue. Integrated Fe3O4 magnetic nanoparticles (MNPs) containing Fe2+ and Fe3+ effectively catalyzes H2O2 to a highly toxic hydroxyl radical (•OH) and provide magnetic targeting. During the course of in vitro and in vivo experiments, GOD-PTL-Lips@MNPs demonstrated remarkable synergistic antitumor efficacy. In particular, in mice receiving a 14 day treatment of GOD-PTL-Lips@MNPs, tumor growth was significantly inhibited, as compared with the control group. Moreover, toxicology study and histological examination demonstrated low biotoxicity of this novel therapeutic approach. In summary, our data suggests great antitumor potential for GOD-PTL-Lips@MNPs which could provide an alternative means of further improving the efficacy of anticancer therapies.

Seedless synthetic branched gold nanoshells for chemo-thermal antitumor therapy.

Gold nanomaterials (GNMs) are used in photothermal therapy due to their superior optical properties and excellent biocompatibility. However, the complex preparation process involving seed-mediated growth limits further clinical applications of GNMs. Herein, a novel one-pot approach to rapidly prepare liposome-based branched gold nanoshells (BGNS) as an antitumor drug nanocarrier is reported. This efficient seedless synthesis realized tunable absorption peaks of BGNS through controlling the concentration of the Au precursor solution, obtaining high absorbance in the near-infrared (NIR) window to achieve a superior photothermal effect. Hyperthermia during NIR laser irradiation can ablate the tumor and trigger drug release to achieve combined treatment. After laser irradiation, the nanocarriers disintegrated into individual gold nanoparticles (size: about 8 nm), which can be metabolized by the kidneys. Cell experiments in vitro and experiments involving mice with tumors have confirmed that the nanodrugs have strong antitumor effects. Such a flexible method provides a universal approach for rapidly preparing liposome-based gold nanoshells, which have the potential for large-scale preparation for further clinical applications.

Nanomagnetic liposome-encapsulated parthenolide and indocyanine green for targeting and chemo-photothermal antitumor therapy.

Aim: To synthesize a drug-delivery system with chemo-photothermal function and magnetic targeting, to validate its antitumor effect. Materials & methods: Parthenolide (PTL), employing chemotherapy and indocyanine green (ICG) providing phototherapy, were encased separately in the lipid and aqueous phases of liposomes (Lips). The Fe3O4 nanoparticles (MNPs), endowing magnetic targeting, were modified on the surface of Lips. The antitumor effects were investigated in vitro and in vivo. Results: ICG-PTL-Lips@MNPs showed outstanding synergistic antitumor efficacy in vitro and in vivo. Especially, after 14-day treatment, the tumor volumes decreased significantly and the biotoxicity was very low. Conclusion: The designed ICG-PTL-Lips@MNPs possess synergistic effects of chemotherapy, photothermal and targeting therapy, which are expected to provide an alternative way to further improve antitumor efficacy.

Sensitive measurement of tumor markers somatostatin receptors using an octreotide-directed Pt nano-flakes driven electrochemical sensor.

Tumor markers play an important role in the early diagnosis and therapeutic effect monitoring of tumors. An electrochemical biosensor was developed based on multi-branched gold nanoshells (BGSs) and octreotide (OCT) functionalized Pt nano-flakes (PtNFs) modified electrodes, which was used for detection of tumor-specific markers to evaluate tumor cells. Sandwich-type nano-hybrid materials were prepared by layer-by-layer modification. First, reduced graphene oxide (RGO) and BGSs were modified as electronic materials onto glassy carbon electrodes (GCE). This modified electrode has strong electron transfer capability and large electrode surface area. The OCT was then anchored to the surface of BGSs to sensitively detect Somatostatin receptors (SSTRs) on the surface of HeLa cells. In addition, PtNFs were synthesized using a dual-template method, and OCT template on the surface of PtNFs, as an adsorption bioprobe, was used to reduce the H2O2 and amplify the electrochemical signal of biosensor. The proposed biosensor can be applied to the quantitative broad linear range of HeLa cells covering from 10 to 1 × 106 cells mL-1 (R2 = 0.9998) and the limit of detection (LOD) was 2 cells mL-1. The experimental results also show that the sensor has good stability, biocompatibility and high selectivity, which has great potential for clinical application.

A chemo-photothermal synergetic antitumor drug delivery system: Gold nanoshell coated wedelolactone liposome.

In this study, an antitumor drug delivery system, gold nanoshell coated wedelolactone liposomes (AuNS-Wed-Lip), were designed and synthesized. In the drug delivery system, wedelolactone liposome and gold-nanoshell were linked by l-cysteine, which had been shown an effective nanocarrier for antitumor drug delivery, on-demand drug release, and phototherapy under near-infrared (NIR) light irradiation. It was capable of absorbing 780-850 nm NIR light and converting light energy to heat rapidly. The hyperthermia promoted wedelolactone release rapidly from the systems. The release amount of AuNS-Wed-Lip under NIR irradiation reached up to 97.34% over 8 h, achieving the on-demand drug release. Moreover, a high inhibition rate up to 95.73% for 143B tumor cells by AuNS-Wed-Lip upon laser irradiation at 808 nm was observed. The excellent inhibition efficacy was also displayed in vivo antitumor study with S180 tumor-bearing mice. The results demonstrated that AuNS-Wed-Lip, as an antitumor drug delivery system, achieved chemo-photothermal synergetic effect, which has great potential in cancer therapy.

A novel exoelectrogen from microbial fuel cell: Bioremediation of marine petroleum hydrocarbon pollutants.

In the past decades, the microbial fuel cell (MFC) technology has caught the attention of the scientific community for its potential in transforming petroleum hydrocarbon (PHC) pollutants directly into electricity through microbial catalyzed anodic. The microbe was one of the most important factors that both influence MFCs and PHC degradation. Here we aimed to identify new microbes to expand the list of microbial species which are both electrogenic and diesel hydrocarbon degrading. In this text, we depicted a strain of microbe named E2, isolated from on the anode surface of MFC, and using diesel as sole carbon source. E2 exhibited electrochemical activity in cyclic voltammetry curve, implicating that it had electrogenic ability. E2 degraded about 50% diesel (3.26 g/L) in maximum during 8 days. Pyrosequencing of 16S rRNA gene of E2 revealed E2 was a sub-strain of Vibrio. Corresponding to salt and alkali tolerant properties of vibrio, the optimal condition for E2 in degrading diesel was 3%-4% in salinity, and pH 8-9 in mineral medium. Collectively, as a member of Gammaproteobacteria class, E2 was novel marine microbe both electricity generation and diesel degradation, which may attract its future application toward artificial microbial community construction in MFC in promoting the PHC pollution removal.

Dual Stimuli-Responsive Peptide-Based Palladium Nano-Lychee Spheres for Synergistic Antitumor Therapy.

The application of peptide-based biomaterials in nanocarriers can effectively reduce toxicity and improve the biocompatibility. In our study, a dual stimuli-responsive peptide-based drug delivery system was designed and synthesized, which was nontoxic and achieved the chem-photothermal therapy synergistic effect. Lanreotide (Lan), a kind of somatostatin analogue, was used as internal template to prepared lychee-shaped palladium (Pd) nanoparticles (Lan-PdNPs). Glutathione (GSH) and doxorubicin (DOX) were combined on the surface of Lan-PdNPs to obtain the nanosystem of Lan-PdNPs@GSH/DOX. Based on the lychee-shaped structures, the system demonstrated higher photothermal conversion performance and photothermal stability. Under NIR laser irradiation, Lan-PdNPs@GSH/DOX could convert light energy to heat in effect and accelerate drug release. Moreover, in acidic conditions, the system also exhibited the pH-responsive drug release. Owing to the synergism, the antitumor effects of Lan-PdNPs@GSH/DOX in vitro and in vivo were superior, and the inhibition ratio was much higher than that of chemotherapy or photothermal therapy alone. The good biocompatibility and nontoxicity of the system also provide the possibility for serving as an antitumor drug candidate.