An albumin-based theranostic nano-agent for dual-modal imaging guided photothermal therapy to inhibit lymphatic metastasis of cancer post surgery

A large variety of cancers are associated with a high incidence of lymph node metastasis, which leads to a high risk of cancer death. Herein, we demonstrate that multimodal imaging guided photothermal therapy can inhibit tumor metastasis after surgery by burning the sentinel lymph nodes (SLNs) with metastatic tumor cells. A near-infrared dye, IR825, is absorbed onto human serum albumin (HSA), which is covalently linked with diethylenetriamine pentaacetic acid (DTPA) molecules to chelate gadolinium. The formed HSA-Gd-IR825 nanocomplex exhibits strong fluorescence together with high near-infrared (NIR) absorbance, and in the mean time could serve as a T1 contrast agent in magnetic resonance (MR) imaging. In vivo bi-modal fluorescence and MR imaging uncovers that HSA-Gd-IR825 after being injected into the primary tumor would quickly migrate into tumor-associated SLNs through lymphatic circulation. Utilizing the strong NIR absorbance of HSA-Gd-IR825, SLNs with metastatic cancer cells can be effectively ablated under exposure to a NIR laser. Such treatment when combined with surgery to remove the primary tumor offers remarkable therapeutic outcomes in greatly inhibiting further metastatic spread of cancer cells and prolonging animal survival. Our work presents an albumin-based theranostic nano-probe with functions of multimodal imaging and photothermal therapy, together with a ‘photothermal ablation assisted surgery’ strategy, promising for future clinical cancer treatment.     

Target-specific near-IR induced drug release and photothermal therapy with accumulated Au/Ag hollow nanoshells on pulmonary cancer cell membranes

Au/Ag hollow nanoshells (AuHNSs) were developed as multifunctional therapeutic agents for effective, targeted, photothermally induced drug delivery under near-infrared (NIR) light. AuHNSs were synthesized by galvanic replacement reaction. We further conjugated antibodies against the epidermal growth factor receptor (EGFR) to the PEGylated AuHNS, followed by loading with the antitumor drug doxorubicin (AuHNS-EGFR-DOX) for lung cancer treatment. AuHNSs showed similar photothermal efficiency to gold nanorods under optimized NIR laser power. The targeting of AuHNS-EGFR-DOX was confirmed by light-scattering images of A549 cells, and doxorubicin release from the AuHNSs was evaluated under low pH and NIR-irradiated conditions. Multifunctional AuHNS-EGFR-DOX induced photothermal ablation of the targeted lung cancer cells and rapid doxorubicin release following irradiation with NIR laser. Furthermore, we evaluated the effectiveness of AuHNS-EGFR-DOX drug delivery by comparing two drug delivery methods: receptor-mediated endocytosis and cell-surface targeting. Accumulation of the AuHNS-EGFR-DOX on the cell surfaces by targeting EGFR turned out to be more effective for lung cancer treatments than uptake of AuHNS-EGFR-DOX. Taken together, our data suggest a new and optimal method of NIR-induced drug release via the accumulation of targeted AuHNS-EGFR-DOX on cancer cell membranes.     

Prussian blue coated gold nanoparticles for simultaneous photoacoustic/CT bimodal imaging and photothermal ablation of cancer

The combination of CT imaging and photoacoustic (PA) imaging represents not only high resolution and ease of forming 3D visual image for locating tissues of interest, but also good soft tissue contrast and excellent high sensitivity, which is very beneficial to the precise guidance for photothermal therapy (PTT). The near infrared (NIR) absorbing Au nanostructures take advantages to operate as a CT contrast agent due to high absorption coefficient of X-ray and outstanding biocompatibility, but show obvious deficiency for PA imaging and PTT because of low photostability. Attacking this problem head on, the Au nanoparticles (NPs) were coated with Prussian blue (PB) which is a typical FDA-approved drug in clinic for safe and effective treatment of radioactive exposure. The obtained core/shell NPs of Au@PB NPs of 17.8 ± 2.3 nm were found to be an excellent photoabsorbing agent for both PTT and PA imaging due to high photostability and high molar extinction coefficient in NIR region. Their gold core of 9.1 ± 0.64 nm ensured a remarkable contrast enhancement for CT imaging. Through a one-time treatment of NIR laser irradiation after intravenous injection of Au@PB NPs, 100 mm³ sized tumors in nude mice could be completely ablated without recurrence. Such versatile nanoparticles integrating effective cancer diagnosis with noninvasive therapy might bring opportunities to future cancer therapy.     

Semimetal nanomaterials of antimony as highly efficient agent for photoacoustic imaging and photothermal therapy

In this study we report semimetal nanomaterials of antimony (Sb) as highly efficient agent for photoacoustic imaging (PAI) and photothermal therapy (PTT). The Sb nanorod bundles have been synthesized through a facile route by mixing 1-octadecane (ODE) and oleyl amine (OAm) as the solvent. The aqueous dispersion of PEGylated Sb NPs, due to its broad and strong photoabsorption ranging from ultraviolet (UV) to near-infrared (NIR) wavelengths, is applicable as a photothermal agent driven by 808 nm laser with photothermal conversion efficiency up to 41%, noticeably higher than most of the PTT agents reported before. Our in vitro experiments also showed that cancer cell ablation effect of PEGylated Sb NPs was dependent on laser power. By intratumoral administration of PEGylated Sb NPs, 100% tumor ablation can be realized by using NIR laser irradiation with a lower power of 1 W/cm² for 5 min (or 0.5 W/cm² for 10 min) and no obvious toxic side effect is identified after photothermal treatment. Moreover, intense PA signal was also observed after intratumoral injection of PEGylated Sb NPs and NIR laser irradiation due to their strong NIR photoabsorption, suggesting PEGylated Sb NPs as a potential NIR PA agent. Based on the findings of this work, further development of using other semimetal nanocrystals as highly efficient NIR agents can be achieved for vivo tumor imaging and PTT.     

Gold nanomaterials conjugated with indocyanine green for dual-modality photodynamic and photothermal therapy

Light-exposure-mediated higher temperatures that markedly accelerate the degradation of indocyanine green (ICG) in aqueous solutions by thermal decomposition have been a serious medical problem. In this work, we present the example of using gold nanorods (Au NRs) and gold nanoparticles (Au NPs) simultaneously serving as photodynamic and photothermal agents to destroy malignant cells. Au NRs and Au NPs were successfully conjugated with hydrophilic photosensitizer, indocyanine green (ICG), to achieve photodynamic therapy (PDT) and photothermal therapy (PTT). We also demonstrated that Au NRs and Au NPs conjugated with ICG displayed high chemical stability and acted as a promising diagnostic probe. Moreover, the photochemical destruction ability would have a gradually increase depending on different sizes of Au NPs. Due to its stability even via higher temperatures mediated by laser irradiation, the combination of PTT and PDT proved to be efficiently killing cancer cells as compared to PTT or PDT treatment alone and enhanced the effectiveness of photodestruction and was demonstrated to enhance its photostability. As a result, the preparation of Au-based nanomaterials conjugated with ICG as well as their use in biomedical applications is valuable developments in multifunctional nanomaterials.     

Self-assembled PEG-IR-780-C13 micelle as a targeting,safe and highly-effective photothermal agent for in vivo imaging and cancer therapy

IR-780, a representative hydrophobic near-infrared (NIR) fluorescence dye, is capable of fluorescently imaging and photothermal therapy in vitro and in vivo. However, insolubility in all pharmaceutically acceptable solvents limits its further biological applications. To increase solubility, we developed a novel self-assembled IR-780 containing micelle (PEG-IR-780-C13) based on the structural modification of IR-780. Briefly, a hydrophilic PEG₂₀₀₀ was modified on the one side of IR-780, and the hydrophobic carbon chain on the other side was extended from C3 to C16 (additional C13 carbon chain). The modification provides a better self-assemble capability, improved water solubility and higher stability. In addition, PEG-IR-780-C13 micelles are specifically targeted to the tumor after intravenous injection and can be used for tumor imaging. The in vitro cell viability assays and in vivo photothermal therapy experiments indicated that CT-26 cells or CT-26 xenograft tumors can be effectively ablated by combining PEG-IR-780-C13 micelles with 808 nm laser irradiation. More importantly, no significant toxicity can be observed after intravenous administration of the therapeutic dose of generated micelles. Overall, our micelles may have the least safety concern while showing excellent treatment efficacy, and thus may be a new photothermal agent potentially useful in clinical applications.     

The in vitro study of Her-2 targeted gold nanoshell liquid fluorocarbon poly lactic-co-glycolic acid ultrasound microcapsule for ultrasound imaging and breast tumor photothermal therapy

Antibody-mediated targeting therapy has been successful in treating patients with breast cancer by improving the specificity and clinical efficacy. In this study, we constructed the human epidermal growth factor receptor-2 (Her2) antibody-conjugated ultrasound contrast agent with lactic-co-glycolic acid (PLGA) as film forming and perfluorocty bromide (PFOB) as internal material, which was coated by gold nanoshell (Her2-PFOB@PLGA@Au), to realize the integration of diagnosis and treatment. The contrast agent was spherical, with the diameter was 256.8 ± 53.4 nm, and had a good dispersion; Ultrasound imaging experiments in vitro showed that the gold nanoshell polylactic acid microcapsule was suitable for ultrasound contrast imaging with the exquisite and uniform dot intensive high echo. The agent had a great photothermal effect under the near-infrared (NIR) with no obvious biological toxicity for both Her2-positive and negative tumor cells; Moreover, both the results of laser scanning confocal microscope (LSCM) and flow cytometer (FCM) demonstrated the great specificity of Her2-PFOB@PLGA@Au conjugating with Her2 positive breast cancer cells (SKBR3). In conclusion, the successful synthesis of the Her2-PFOB@PLGA@Au microcapsule, offered a new therapeutic strategy of combining diagnosis with therapy for fighting against the breast cancer.     

Au capped magnetic core/mesoporous silica shell nanoparticles for combined photothermo-/chemo-therapy and multimodal imaging

Uniform Au NRs-capped magnetic core/mesoporous silica shell nanoellipsoids (Au NRs-MMSNEs) were prepared by coating a uniform layer of Au NRs on the outer surface of a magnetic core/mesoporous silica shell nanostructure, based on a two-step chemical self-assembly process. This multifunctional nanocomposite integrate simultaneous chemotherapy, photo-thermotherapy, in vivo MR-, infrared thermal and optical imaging into one single system. The obtained multifunctional nanoellipsoids showed very low cytotoxicity, and the cancer cell uptake and intracellular location of the nanoellipsoids were observed by confocal laser scanning microscopy and bio-TEM. Importantly, the prepared multifunctional nanoellipsoids showed high doxorubicin loading capacity and pH value-responsive release mainly due to the electrostatic interaction between DOX molecules and mesoporous silica surface. Besides, a synergistic effect of combined chemo- and photo-thermo therapy was found at moderate power intensity of NIR irradiation based on the DOX release and the photothermal effect of Au NRs.     

SNAIL induces epithelial-to-mesenchymal transition in a human pancreatic cancer cell line (BxPC3) and promotes distant metastasis and invasiveness in vivo

SNAIL, a potent repressor of E-cadherin expression, plays a key role in inducing epithelial-to-mesenchymal transition (EMT) in epithelial cells. During EMT, epithelial cells lose cell polarity and adhesion, and undergo drastic morphological changes acquiring highly migratory abilities. Although there is increasing evidence that EMT is involved in the progression of some human cancers, its significance in the progression of pancreatic cancer remains elusive. In Panc-1, a well-known human pancreatic cancer cell line in which EMT is triggered by TGF-β1 treatment, SNAIL and vimentin are highly expressed, whereas E-cadherin expression is scant. In contrast, another human pancreatic cancer cell line, BxPC3, in which SNAIL expression is not detected, has high levels of E-cadherin expression and does not undergo EMT upon TGF-β1 treatment. After transfecting the SNAIL gene into BxPC3, however, the cells undergo EMT with remarkable alterations in cell morphology and molecular expression patterns without the addition of any growth factors. Furthermore, in an orthotopic transplantation model using SCID mice, SNAIL-transfected BxPC3 displayed highly metastatic and invasive activities. In the immunohistochemical analysis of the tumor derived from the SNAIL-expressing BxPC3, alterations suggestive of EMT were observed in the invasive tumor front. SNAIL enabled BxPC3 to undergo EMT, endowing it with a highly malignant potential in vivo. These results indicate that SNAIL-mediated EMT may be relevant in the progression of pancreatic cancer, and SNAIL could be a molecular target for a pancreatic cancer intervention.     

转化生长因子-β1的Smad4非依赖性途径对胰腺癌细胞生长的影响

目的探讨转化生长因子(TGF)-β1过表达对Smad4纯合性缺失的胰腺癌细胞生长的影响。方法将含TGF-β1的真核表达载体转染到人胰腺癌细胞BxPC3中,通过流式细胞仪、生长曲线以及细胞迁移试验观察其对BxPC3生物学行为的影响。用Western印迹法检测TGF-β1对BxPC3细胞中p21WAF/CLIP1表达的影响。结果转染TGF-β1基因的BxPC3细胞的形态发生明显改变,其生长速度自第4天开始较转染空载体pcDNA3的阴性对照组减慢。发现BxPC3细胞组S期细胞(27.53±0.02)%与pcDNA3组(26.32±0.01)%的比例均高于TGF-β1组(17.01±0.03)%,P<0.01,表明TGF-β1阻止细胞进入S期。细胞迁移试验表明转染的细胞运动能力明显增加。Western印迹法检测表明p21WAF/CLIP1的表达也相应增高。结论TGF-β1的Smad4非依赖性途径通过增强p21WAF/CLIP1的表达使细胞阻滞于G-G期,从而抑制细胞生长,并且该通路能诱导上皮细胞向间叶细胞转变。     

Synthesis,characterization, and in vitro evaluation of targeted gold nanoshelled poly(d,l-lactide-co-glycolide) nanoparticles carrying anti p53 antibody as a theranostic agent for ultrasound contrast imaging and photothermal therapy

Breast cancer is the leading cause of cancer-related deaths in women and earlier detection can substantially reduce deaths from breast cancer. Polymers with targeted ligands are widely used in the field of molecular ultrasound imaging and targeted tumor therapy. In our study, the nanotheranostic agent was fabricated through filling perfluoropropane (C₃F₈) into poly(d,l-lactic-co-glycolic acid) nanoparticles (PLGA NPs), followed by the formation of gold nanoshell on the surface, then conjugated with anti p53 antibody which has high specificity with the p53 protein overexpressing in breast cancer. The average diameter of the gold nanoshelled PLGA NPs carrying anti p53 antibody (p53-PLGA@Au NPs) was 247 ± 108.2 nm. The p53-PLGA@Au NPs had well-defined spherical morphology and hollow interiors observed by electron microscope, and had a good photothermal effect under the irradiation of an 808 nm laser. The results of laser scanning confocal microscope (LSCM) and flow cytometer (FCM) indicated the specific targeting of p53-PLGA@Au NPs conjugating with breast cancer MCF-7 cells overexpressing p53 protein in vitro. Also the ultrasound imaging experiments in vitro showed that p53-PLGA@Au NPs were suitable for ultrasound contrast imaging. In conclusion, the p53-PLGA@Au NPs are demonstrated to be novel targeted UCAs and may have potential applications in the early diagnosis and targeted near-infrared (NIR) photothermal therapy of breast cancer in the future.     

RGD peptides and monoclonal antibodies, antagonists of alpha(v)-integrin, enter the cells by independent endocytic pathways.

Cyclic synthetic peptides containing the arginine-glycine-aspartate motif (cRGD) and monoclonal antibodies (mAbs) targeted for individual integrins have been developed as potential therapeutic drugs for the treatment of several diseases. We showed that a cRGD peptide targeted for alpha(v)beta(3) was internalized in alpha(v)-integrin expressing and nonexpressing melanoma cells by an integrin independent fluid-phase endocytosis pathway that does not alter the number of functional integrin receptors at the cell surface. In contrast, a blocking mAb directed to alpha(v) was internalized by an integrin-dependent endocytosis pathway that reduced the number of functional integrin receptors at the cell surface. We prove that melanoma cells pretreated with the mAb do not readhere to the substrate, whereas cells pretreated with cRGD peptide retain their readhesion capacity. Given the growing importance of RGD peptides, knowledge of these cellular mechanisms is required to improve the development of antiangiogenic and anti-inflammatory drugs.     

Radionuclide 131I labeled reduced graphene oxide for nuclear imaging guided combined radio- and photothermal therapy of cancer

Nano-graphene and its derivatives have attracted great attention in biomedicine, including their applications in cancer theranostics. In this work, we develop 131I labeled, polyethylene glycol (PEG) coated reduced nano-graphene oxide (RGO), obtaining 131I-RGO-PEG for nuclear imaging guided combined radiotherapy and photothermal therapy of cancer. Compared with free 131I, 131IRGO- PEG exhibits enhanced cellular uptake and thus improved radio-therapeutic efficacy against cancer cells. As revealed by gamma imaging, efficient tumor accumulation of 131I-RGO-PEG is observed after its intravenous injection. While RGO exhibits strong near-infrared (NIR) absorbance and could induce effective photothermal heating of tumor under NIR light irradiation, 131I is able to emit high-energy X-ray to induce cancer killing as the result of radio ionization effect. By utilizing the combined photothermal therapy and radiotherapy, both of which are delivered by a single agent 131IRGO- PEG, effective elimination of tumors is achieved in our animal tumor model experiments. Toxicology studies further indicate that 131I-RGO-PEG induces no appreciable toxicity to mice at the treatment dose. Our work demonstrates the great promise of combing nuclear medicine and photothermal therapy as a novel therapeutic strategy to realize synergistic efficacy in cancer treatment.     

Indocyanine Green-Glycogen Conjugates for Near-Infrared-Triggered Photothermal Cancer Therapy

Photothermal reagents sensitive to near-infrared (NIR) light are promising imaging agents and therapeutics for anticancer applications because of the deep tissue penetration of NIR light, allowing for spatiotemporal control over the therapeutic activity, with minimal damage to normal tissues. Herein, a new class of NIR-sensitive biopolymer-based nanoparticles is presented by covalently conjugating indocyanine green (ICG) onto the surface of naturally occurring glycogen nanoparticles. The resulting ICG-glycogen conjugates exhibit a markedly enhanced aqueous stability in comparison to free ICG molecules. Furthermore, an efficient light-to-heat conversion is enabled by ICG-glycogen conjugates, as evidenced by the elevated temperatures of their aqueous solutions upon exposure to NIR light. Critically, ICG-glycogen conjugates are capable of cell internalization, and under NIR irradiation the effective eradication of breast cancer cells, demonstrating their potential in photothermal therapy for cancer.     

NIR-light-induced surface-enhanced Raman scattering for detection and photothermal/photodynamic therapy of cancer cells using methylene blue-embedded gold nanorod@SiO2 nanocomposites

Methylene blue-loaded gold nanorod@SiO₂ (MB-GNR@SiO₂) core@shell nanoparticles are synthesized for use in cancer imaging and photothermal/photodynamic dual therapy. For the preparation of GNR@SiO₂ nanoparticles, we found that the silica coating rate of hexadecylcetyltrimethylammonium bromide (CTAB)-capped GNRs is much slower than that of PEGylated GNRs due to the densely coated CTAB bilayer. Encapsulated MB molecules have both monomer and dimer forms that result in an increase in the photosensitizing effect through different photochemical pathways. As a consequence of the excellent plasmonic properties of GNRs at near-infrared (NIR) light, the embedded MB molecules showed NIR light-induced SERS performance with a Raman enhancement factor of 3.0 × 10¹⁰, which is enough for the detection of a single cancer cell. Moreover, the MB-GNR@SiO₂ nanoparticles exhibit a synergistic effect of photodynamic and photothermal therapies of cancer under single-wavelength NIR laser irradiation.     

Folate-modified,indocyanine green-loaded lipid-polymer hybrid nanoparticles for targeted delivery of cisplatin

Cisplatin is a potent antitumor drug, which is widely applied in clinical cancer treatment. However, cisplatin can hardly distinguish between healthy tissue and tumor tissue, resulting in serious toxic side effects. Indocyanine green (ICG) is a FDA-approved near-infrared (NIR) fluorescence dye which has been used in photothermal therapy and optically mediated diagnostic, but the application of ICG is limited by its concentration-dependent aggregation, poor aqueous stability in vitro, lack of target specificity and rapid elimination from the body. Herein, to overcome these limitations of cisplatin and ICG, we fabricated folate-modified, cisplatin, ICG-loaded lipid-polymer hybrid nanoparticles (FCINPs) using a single-step sonication method. The FCINPs exhibited well-defined monodispersity, significant stability and excellent NIR penetration ability. The intracellular uptake experiment showed that the targeting efficacy of the FCINPs was more effective in folate receptors (FRs) over-expressing MCF-7 cells than FRs negative A549 cells. In addition, compared with chemo or photothermal treatment alone, the treatment of FCINPs in combination with 808 nm NIR laser irradiation can significantly induce the apoptosis and necrosis of MCF-7 cells. These findings indicated that the FCINPs would be a promising nanosized drug formulation for tumor-targeted therapy in the future.     

Photothermal cancer therapy and imaging based on gold nanorods

Gold nanorods (GNRs), which strongly absorb near-infrared (NIR) light, have shown great potential in fields of biomedical application. These include photothermal therapy, molecular imaging, biosensing, and gene delivery, especially for the treatment of diseased tissues such as cancer. These biomedical applications of GNRs arise from their various useful properties; photothermal (nanoheater) properties, efficient large scale synthesis, easy functionalization, and colloidal stability. In addition, GNRs do not decompose and have an enhanced scattering signal and tunable longitudinal plasmon absorption which allow them to be used as a stable contrast agent. Therefore, GNRs are also promising theranostic agents, combining both tumor diagnosis and treatment. In this review, we discuss the recent progress of in vitro and in vivo explorations of the diagnostic and therapeutic applications of GNRs as a component of cancer therapy.     

Hyaluronic acid-modified Fe3O4@Au core/shell nanostars for multimodal imaging and photothermal therapy of tumors

Development of multifunctional theranostic nanoplatforms for diagnosis and therapy of cancer still remains a great challenge. In this work, we report the use of hyaluronic acid-modified Fe₃O₄@Au core/shell nanostars (Fe₃O₄@Au-HA NSs) for tri-mode magnetic resonance (MR), computed tomography (CT), and thermal imaging and photothermal therapy of tumors. In our approach, hydrothermally synthesized Fe₃O₄@Ag nanoparticles (NPs) were used as seeds to form Fe₃O₄@Au NSs in the growth solution. Further sequential modification of polyethyleneimine (PEI) and HA affords the NSs with excellent colloidal stability, good biocompatibility, and targeting specificity to CD44 receptor-overexpressing cancer cells. With the Fe₃O₄ core NPs and the star-shaped Au shell, the formed Fe₃O₄@Au-HA NSs are able to be used as a nanoprobe for efficient MR and CT imaging of cancer cells in vitro and the xenografted tumor model in vivo. Likewise, the NIR absorption property enables the developed Fe₃O₄@Au-HA NSs to be used as a nanoprobe for thermal imaging of tumors in vivo and photothermal ablation of cancer cells in vitro and xenografted tumor model in vivo. This study demonstrates a unique multifunctional theranostic nanoplatform for multi-mode imaging and photothermal therapy of tumors, which may find applications in theranostics of different types of cancer.     

FA and cRGD dual modified lipid-polymer nanoparticles encapsulating polyaniline and cisplatin for highly effective chemo-photothermal combination therapy

A combination of chemotherapy and photothermal therapy as a promising strategy has exhibited noticeable therapeutic effect on cancer therapy. To ensure the exertion of synergistic effect on a tumor region, a multifunctional vehicle for selectively delivering therapeutic agent into tumor cells is highly desirable. Thus, folate-poly (ethylene glycol)-distearoylphosphatidylcholine (FA-PEG-DSPE), cRGD [cyclic (Arg-Gly-Asp-D-Phe-Lys)]-PEG-DSPE and lecithin were employed to develop dual modified nanoparticles (FA/cRGD-PNPs) encapsulating polyaniline and cisplatin by a film-ultrasonic dispersion method. The FA/cRGD-PNPs showed a uniform size of 102.7 nm, remarkable stability and monodispersity, and highly localized temperature respond. Compared to chemo or photothermal treatment alone, the combined treatment on cells in vitro significantly suppressed the survival rate of MDA-MB-231 cells (1.87%) and MGC-803 cells (2.37%) treated for 48 h. The results further indicated the induced cell apoptosis rate of MDA-MB-231 cells reached to 92.6% with treatment for 24 h. Hence, our research highlights the great potential in drug delivery and the combination of chemotherapy and photothermal therapy.     

Unexpected high photothemal conversion efficiency of gold nanospheres upon grafting with two-photon luminescent ruthenium(II) complexes: A way towards cancer therapy?

The design and development of functional hybrid nanomaterials is currently a topic of great interest in biomedicine. Herein we investigated the grafting of Ru(II) polypyridyl complexes onto gold nanospheres (Ru@AuNPs) to improve the particles' near infrared (NIR) absorption, and ultimately allow for application in photothermal cancer therapy. As demonstrated in this article, these ruthenium(II) complexes could indeed significantly enhance gold nanospheres' two-photon luminescence (PTL) intensity and photothermal therapy (PTT) efficiency. The best dual functional nanoparticles of this study were successfully used for real-time luminescent imaging-guided PTT in live cancer cells. Furthermore, in vivo tumor ablation was achieved with excellent treatment efficacy under a diode laser (808 nm) irradiation at the power density of 0.8 W/cm² for 5 min. This study demonstrates that the coupling of inert Ru(II) polypyridyl complexes to gold nanospheres allows for the enhancement of two-photon luminescence and for efficient photothermal effect.