Monodisperse Sub-100 nm Au Nanoshells for Low-Fluence Deep-Tissue Photoacoustic Imaging.

Nanoparticles with high absorption cross sections will advance therapeutic and bioimaging nanomedicine technologies. While Au nanoshells have shown great promise in nanomedicine, state-of-the-art synthesis methods result in scattering-dominant particles, mitigating their efficacy in absorption-based techniques that leverage the photothermal effect, such as photoacoustic (PA) imaging. We introduce a highly reproducible synthesis route to monodisperse sub-100 nm Au nanoshells with an absorption-dominant optical response. Au nanoshells with 48 nm SiO2 cores and 7 nm Au shells show a 14-fold increase in their volumetric absorption coefficient compared to commercial Au nanoshells with dimensions commonly used in nanomedicine. PA imaging with Au nanoshell contrast agents showed a 50% improvement in imaging depth for sub-100 nm Au nanoshells compared with the smallest commercially available nanoshells in a turbid phantom. Furthermore, the high PA signal at low fluences, enabled by sub-100 nm nanoshells, will aid the deployment of low-cost, low-fluence light-emitting diodes for PA imaging.

Ablation of Venous Malformations by Photothermal Therapy with Intravenous Gold Nanoshells.

Venous malformations (VMs) consist of hugely enlarged and dysmorphic veins. These lesions cause significant disfigurement, pain, and complications such as bleeding and coagulopathy. Pharmacotherapy for the treatment of VMs has limited efficacy and potentially limiting toxicity. Current treatment for patients with VMs entails life-long pharmacotherapy or surgical procedures. Here we explored whether intravenously administered agents can be used to destroy VMs by photothermal therapy (PTT), using gold nanoshells (AuNSs) that generated heat following irradiation with near-infrared (NIR) light. In a murine model of VMs, intravenous AuNSs accumulated within the VMs. Irradiation of the VMs induced marked regression and even elimination. Nanoparticle-based photothermal therapy can provide effective therapy for VMs, which are otherwise relatively refractory to treatment.

Biomimetic Gold Nanoshell-Loaded Macrophage for Photothermal Biomedicine.

The purpose of this study was to investigate the effect of photothermal treatment (PTT) with gold nanoshell (ANS) using a macrophage-mediated delivery system in a head and neck squamous cell carcinoma (HNSCC) cell line. To achieve this, ANS-loaded rat macrophages (ANS-MAs) were prepared via the coculture method with ANS. The human HNSCC (FaDu cell) and macrophage (rat macrophage; NR8383 cell) hybrid spheroid models were generated by the centrifugation method to determine the possibility of using ANS-MAs as a cancer therapy. These ANS-MAs were set into the tumor and macrophage hybrid spheroid model to measure PTT efficacy. Kinetic analysis of the spheroid growth pattern revealed that this PTT process caused a decreasing pattern in the volume of the hybrid model containing ANS-MAs (p < 0.001). Comparison with empty macrophages showed harmony between ANS and laser irradiation for the generation of PTT. An annexin V/dead cell marker assay indicated that the PTT-treated hybrid model induced increasing apoptosis and dead cells. Further studies on the toxicity of ANS-MAs are needed to reveal whether it can be considered biocompatible. In summary, the ANS was prepared with a macrophage as the delivery method and protective carrier. The ANS was successfully localized to the macrophages, and their photoabsorption property was stationary. This strategy showed significant growth inhibition of the tumor and macrophage spheroid model under NIR laser irradiation. In vivo toxicology results suggest that ANS-MA is a promising candidate for a biocompatible strategy to overcome the limitations of fabricated nanomaterials. This ANS-MA delivery and PTT strategy may potentially lead to improvements in the quality of life of patients with HNSCC by providing a biocompatible, minimally invasive modality for cancer treatment.

Synthetic Immunogenic Cell Death Mediated by Intracellular Delivery of STING Agonist Nanoshells Enhances Anticancer Chemo-immunotherapy.

Many favorable anticancer treatments owe their success to the induction immunogenic cell death (ICD) in cancer cells, which results in the release of endogenous danger signals along with tumor antigens for effective priming of anticancer immunity. We describe a strategy to artificially induce ICD by delivering the agonist of stimulator of interferon genes (STING) into tumor cells using hollow polymeric nanoshells. Following intracellular delivery of exogenous adjuvant, subsequent cytotoxic treatment creates immunogenic cellular debris that spatiotemporally coordinate tumor antigens and STING agonist in a process herein termed synthetic immunogenic cell death (sICD). sICD is indiscriminate to the type of chemotherapeutics and enables colocalization of exogenously administered immunologic adjuvants and tumor antigens for enhanced antigen presentation and anticancer adaptive response. In three mouse tumor models, sICD enhances therapeutic efficacy and restrains tumor progression. The study highlights the benefit of delivering STING agonists to cancer cells, paving ways to new chemo-immunotherapeutic designs.

Smart Plasmonic Nanozyme Enhances Combined Chemo-photothermal Cancer Therapy and Reveals Tryptophan Metabolic Apoptotic Pathway.

Regulation of the tumor microenvironment is considered to be an intelligent strategy for cancer therapeutics, but the related metabolic pathways of cell apoptosis still remain a great challenge. Herein, by applying multifunctional carbon dot-decorated Ag/Au bimetallic nanoshells (CDs-Ag/Au NSs, CAANSs) nanoprobes as smart plasmonic nanozymes for combined chemo-photothermal cancer therapy, we achieved a high efficiency in cancer cell therapy and revealed a tryptophan (Trp) metabolic apoptotic pathway. In addition to high photothermal conversion efficiency, the CAANSs can act as a smart nanozyme to catalyze intracellular H2O2 to the cytotoxic reactive oxygen species (ROS) of superoxide anion (·O2-), in response to mild acidic cancerous cell microenvironment to damage cellular DNA. More importantly, the Trp metabolic pathway during the combined chemo-photothermal therapy has revealed that the Trp participates in an oxidative stress process, which can be decomposed to produce H2O2 and further formed into superoxide anions to kill cells under the catalytic nanomedicine process. The current work provides an effective platform for cancer therapeutics and is promising for cancer-related molecular biology studies.

Selective radiofrequency ablation of tumor by magnetically targeting of multifunctional iron oxide-gold nanohybrid.

PURPOSE: Radiofrequency (RF) ablation therapy is of great interest in cancer therapy as it is non-ionizing radiation and can effectively penetrate into the tissue. However, the current RF ablation technique is invasive that requires RF probe insertion into the tissue and generates a non-specific heating. Recently, RF-responsive nanomaterials such as gold nanoparticles (AuNPs) and iron oxide nanoparticles (IONPs) have led to tremendous progress in this area. They have been found to be able to absorb the RF field and induce a localized heating within the target, thereby affording a non-invasive and tumor-specific RF ablation strategy. In the present study, for the first time, we used a hybrid core-shell nanostructure comprising IONPs as the core and AuNPs as the shell (IO@Au) for targeted RF ablation therapy. Due to the magnetic core, the nanohybrid can be directed toward the tumor through a magnet. Moreover, IONPs enable the nanohybrid to be used as a magnetic resonance imaging (MRI) contrast agent. RESULTS: In vitro cytotoxicity experiment showed that the combination of IO@Au and 13.56-MHz RF field significantly reduced the viability of cancer cells. Next, during an in vivo experiment, we demonstrated that magnetically targeting of IO@Au to the tumor and subsequent RF exposure dramatically suppressed the tumor growth. CONCLUSION: Therefore, the integration of targeting, imaging, and therapeutic performances into IO@Au nanohybrid could afford the promise to improve the effectiveness of RF ablation therapy.

Comprehensive Evaluation of Degradable and Cost-Effective Plasmonic Nanoshells for Localized Photothermolysis of Cancer Cells.

Integrating the concept of biodegradation and light-triggered localized therapy in a functional nanoformulation is the current approach in onco-nanomedicine. Morphology control with an enhanced photothermal response, minimal toxicity, and X-ray attenuation of polymer-based nanoparticles is a critical concern for image-guided photothermal therapy. Herein, we describe the simple design of cost-effective and degradable polycaprolactone-based plasmonic nanoshells for the integrated photothermolysis as well as localized imaging of cancer cells. The gold-deposited polycaprolactone-based plasmonic nanoshells (AuPCL NS) are synthesized in a scalable and facile way under ambient conditions. The synthesized nanoshells are monodisperse, fairly stable, and highly inert even at five times (250 µg/mL) the therapeutic concentration in a week-long test. AuPCL NS are capable of delivering standalone photothermal therapy for the complete ablation of cancer cells without using any anticancerous drugs and causing toxicity. It delivers the same therapeutic efficacy to different cancer cell lines, irrespective of their chemorefractory status and also works as a potential computed tomography contrast agent for the integrated imaging-directed photothermal cancer therapy. High biocompatibility, degradability, and promising photothermal efficacy of AuPCL NS are attractive aspects of this report that could open new horizons of localized plasmonic photothermal therapy for healthcare applications.

Inorganic Nanoshell-Stabilized Liquid Metal for Targeted Photonanomedicine in NIR-II Biowindow.

Gallium and gallium-based alloys, typical types of liquid metals with unique physiochemical properties, are emerging as a next generation of functional materials in versatile biomedical applications. However, the exploration of their biomedical performance is currently insufficient, and their intrinsic low oxidative resistance is a key factor blocking their further clinical translation. Herein, we report on the surface engineering of liquid metal-based nanoplatforms by an inorganic silica nanoshell based on a novel but facile sonochemical synthesis for highly efficient, targeted, and near-infrared (NIR)-triggered photothermal tumor hyperthermia in the NIR-II biowindow. The inorganic silica-shell engineering of liquid metal significantly enhances the photothermal performance of the liquid metal core as reflected by enhanced NIR absorption, improved photothermal stability by oxidation protection, and abundant surface chemistry for surface-targeted engineering to achieve enhanced tumor accumulation. Systematic in vitro cell-level evaluation and in vivo tumor xenograft assessment demonstrate that (Arg-Gly-Asp) RGD-targeted and silica-coated nanoscale liquid metal substantially induces phototriggered cancer-cell death and photothermal tumor eradication, accompanied by high in vivo biocompatibility and easy excretion out of the body. This work provides the first paradigm for surface-inorganic engineering of liquid metal-based nanoplatforms for achieving multiple desirable therapeutic performances, especially for combating cancer.

Rodlike MSN@Au Nanohybrid-Modified Supermolecular Photosensitizer for NIRF/MSOT/CT/MR Quadmodal Imaging-Guided Photothermal/Photodynamic Cancer Therapy.

Recently, rodlike nanomaterials with specific aspect ratio for efficient cellular uptake have received enormous attention. For functional nanomaterials, such as photothermal agents, large surface areas for their rod-shaped exterior that increase the amount of light absorbed would lead to a higher absorption coefficient as well as drug-loading property. In this project, we coated rodlike mesoporous silica with gold nanoshells (MSNR@Au hybrid), modifying them with ultrasmall gadolinium (Gd)-chelated supramolecular photosensitizers, TPPS4 (MSNR@Au-TPPS4(Gd)), which could be applied to near-infrared fluorescence/multispectral optoacoustic tomography/computed tomography/magnetic resonance imaging and imaging-guided remotely controlled photothermal (PTT)/photodynamic (PDT) combined antitumor therapy. Gold nanoshells, as a perfect PTT agent, were used to assemble the rodlike mesoporous silica nanoparticles with larger superficial area and higher drug loading, thus obtaining the MSNR@Au hybrid. HS-ß-CD, which was used as the host, was adsorbed on the gold nanoshell (MSNR@Au-ß-CD) to link TPPS4(Gd) through the host-guest reaction, thus forming CD-TPPS4 supramolecular photosensitizers (supraPSs). Compared with conventional PSs, supraPSs have host screens, which could reduce the self-aggregation of TPPS4, and consequently generate 1O2 with high efficiency. The in vivo quadmodal imaging of MSNR@Au-TPPS4(Gd) nanoparticles revealed an intensive tumor uptake effect after injection. The in vivo antitumor efficacy further testified that the synergistic therapy, which was more efficient than any other monotherapy, exhibited an excellent tumor inhibition therapeutic effect. As a result, this encourages to further explore multifunctional theranostic nanoparticles based on gold shells for combined cancer therapy.

Dual-template cascade synthesis of highly multi-branched Au nanoshells with ultrastrong NIR absorption and efficient photothermal therapeutic intervention.

With the rapid development of photothermal therapy (PTT) in cancer treatment, it is necessary to obtain effective plasma-responsive tunable photothermal transducing agents. Inspired by the peptide-directed hierarchical mineralized Ag nanocages (Ag NCs), scientists designed a new duel-template cascade preparation method, and novel unique multi-branched gold nanoshells (BGSs) were successfully prepared under mild conditions using green strategy. The length, density and diameter of the branches were tuned, which led to the adjustment of the surface plasma response of the nanostructure. Because of the hierarchical structure and anisotropic surface, an obvious red shift of the local surface plasmon resonance spectrum was observed for the branched Au nanoshells. The excellent photothermal conversion efficiency (70.9%) and photo-induced heating responsive curves proved the superior photothermal conversion performance and photothermal stability of BGSs. The in vitro and in vivo results indicated that the heat generated by the intense NIR absorption of BGSs can selectively destroy cancer cells under laser irradiation. The nanostructures with ultrastrong absorption have promising prospects in tumor therapy.

Evaluation of theranostic perspective of gold-silica nanoshell for cancer nano-medicine: a numerical parametric study.

Using gold-silica nanoshell as a reference nano-agent, this work has performed preliminary numerical parametric study to investigate the feasibility and if feasible the efficiency of using a single nano-agent to achieve theranostic goals. In total, seven generics of gold-silica nanoshells have been tested including the R[50,10] (radius of the silica core is 50 nm and thickness of the gold shell is 10 nm), R[40,15], R[55,25], R[40,40], R[75,40], R[104,23], and R[154,24] nanoshells. A planar tissue model has been constructed as the platform for parametric study. For mathematical modeling, radiant transport equation (RTE) has been applied to describe the interactions among laser lights, the hosting tissue, and the hosted nanoshells and Penne's bio-heat equation has been applied to describe the hyperthermia induced by such interactions. Effects of different nanoshell generics on the diffuse reflectance signal and hyperthermia temperature transition have been simulated, basing on which the potential of a certain nanoshell generic as theranostic nano-agent has been evaluated. It has been found that it is highly feasible for gold-silica nanoshells to be engineered for theranostic purpose and nanoshell generics that are preferentially scattering should be explored for good theranostic candidates. On the condition that nanoshell generic with the right optical properties has been located, a moderate nanoshell retention in the target tissue site is already sufficient to induce effective theranostic effects, which indicates that theranostic nano-medicine might not have a stringent requirement for the delivery technique. Among nanoshells that have been tested, the R[55,25] nanoshell seems to be a promising candidate as theranostic nano-agent. Further testing on it is highly recommended. Nanoshells that are preferentially absorbing such as the R[50,10] and R[40,15] nanoshells are efficient photothermal agent and could be used for therapeutic purpose only. However, it is not recommended that preferentially absorbing nanoshells being used for theranostic purpose due to possible negative effects such nanoshells might bring to the diffuse reflectance signal.

Total Aqueous Synthesis of Au@Cu2-x S Core-Shell Nanoparticles for In Vitro and In Vivo SERS/PA Imaging-Guided Photothermal Cancer Therapy.

Both accurate tumor navigation and nanostructures with high photothermal (PT) conversion efficiency are important but remain challenging to achieve in current biomedical applications. This study reports an anion exchange-based facile and green approach for synthesizing Au@Cu2-x S core-shell nanoparticles (NPs) in an aqueous system. In addition to the PT effect of the suggested NPs, the surface-enhanced Raman scattering (SERS) is also significantly improved due to the tailored localized surface plasmon resonance coupling between the Au metal core and the Cu2-x S semiconductor shell. Using an epitaxial strategy, Au@Cu2 O NPs are first obtained by the in situ reduction of cupric hydroxide on a cresyl violet acetate-coated Au core; then, Au@Cu2-x S NPs are obtained via anion exchange between the S2- and Cu2 O shell. Both the Cu/S atomic ratio and the Cu2-x S shell thickness can be adjusted conveniently. Hence, the ideal integration of the plasmonic Au core and Cu2-x S shell into a single unit is conducive not only to highly efficient PT conversion but also to the construction of a SERS-based navigator. This new type of SERS-guided NP, with enhanced photoacoustic signals, is an important candidate for both accurate tumor navigation and nondestructive PT treatment guided in vivo by two modes of optical imaging.

Detection and Inhibition of Bacteria on a Dual-Functional Silver Platform.

Detection and inhibition of bacteria are universally required in clinics and daily life for health care. Developing a dual-functional material is challenging and in demand, engaging advanced applications for both defined bioanalysis and targeted biotoxicity. Herein, magnetic silver nanoshells are designed as a multifunctional platform for the detection and inhibition of bacteria. The optimized magnetic silver nanoshells enable direct laser desorption/ionization mass spectrometry based metabolic analysis of bacteria (≈10 µL-1 ), in complex biofluids. The serum infection process (0-10 h) is monitored by statistics toward clinical classification. Moreover, magnetic silver nanoshells facilitate surface adhesion on bacteria due to nanoscale surface roughness and thus display long-term antibacterial effects. Bacteria metabolism is studied with metabolic biomarkers (e.g., malate and lysine) identified during inhibition, showing cell membrane destruction and dysfunctional protein synthesis mechanisms. This work not only guides the design of material-based approaches for bioanalysis and biotoxicity, but contributes to bacteria-related diagnosis by using specific metabolic biomarkers for sensitive detection and new insights by monitoring metabolomic change of bacteria for antibacterial applications.

Biodegradable hypocrellin derivative nanovesicle as a near-infrared light-driven theranostic for dually photoactive cancer imaging and therapy.

Photoactive agents based on natural products have attracted substantial attention in clinical applications because of their distinct biological activity, molecular structure multiformity, and low biotoxicity. Herein, we initially modify hypocrellin B (HB) with 1,2-diamino-2-methyl propane to form near-infrared (NIR) light (>700 nm)-responsive amino-substituted HB derivative (DPAHB). The DPAHB exhibit broad absorption (400-800 nm), NIR emission (maximum emission peak at 710 nm), and high singlet oxygen (1O2) quantum yield (∼0.33) under NIR light (721 nm) irradiation. After self-assembly by using DPAHB with PEG-PLGA, the as-prepared nanovesicles (DPAHB NVs) retain efficient 1O2 generation, more interestingly, show high photothermal conversion efficiency (∼0.24) under NIR light (721 nm) irradiation for synergistic photodynamic therapy (PDT) and photothermal therapy toward hypoxic tumor. The DPAHB NVs can not only be as a fluorescence/photoacoustic imaging agent but also exhibit an even stronger PDT efficiency than that of chlorin e6 (a widely used classic photosensitizer). In vitro and in vivo studies demonstrate that DPAHB NVs possess high photothermal stability, enhanced tumor accumulation, and suitable biodegradation rate, thus, show a highly promising clinical potential as a new photoactive agent for cancer therapy.

Multifunctional Porous Iron Oxide Nanoagents for MRI and Photothermal/Chemo Synergistic Therapy.

Nanoagents of integrating multiple imaging and therapeutic modalities have attracted tremendous attention for biomedical applications. Herein, we synthesize porous hollow Fe3O4 as a theranostic agent for MRI and combined photothermal/chemo cancer therapy. The as-prepared porous iron oxide nanoagents allow for T2-weighted MR imaging. Interestingly, we demonstrate that the porous structure endows the nanoagents an outstanding photothermal property for cancer cell killing, in comparison with other types of iron oxide nanomaterials. Under the exposure of an NIR laser, the heat produced by porous Fe3O4 can accelerate the release of the loaded drug (e.g., DOX) to enhance chemotherapeutic efficacy, promoting the ablation of cancer cells with synergistic photothermal/chemotherapy.

Glycol chitosan assisted in situ reduction of gold on polymeric template for anti-cancer theranostics.

Multifunctional biodegradable nanomaterials that could be used for both imaging and therapy are being researched extensively. A simple technique to synthesize multifunctional nanoparticles without compromising on any of their functionality is a challenge. We have attempted to optimize a two-step procedure of gold coated polymeric template involving 1) Single pot synthesis of PLGA nanoparticles with cationic surface charge using glycol chitosan and 2) in situ gold coating for formation of gold coated PLGA nanoshell (AuPLGA-NS). These gold-coated PLGA nanoparticles were explored for photothermal therapy (PTT) and as X-ray/CT contrast agents. Biocompatibility and photothermal cytotoxicity of AuPLGA-NS were evaluated in-vitro and results confirmed the therapeutic efficacy of these particles resulting in 80% cancer cell death. Besides, it also showed potential X-ray/CT imaging ability with contrast equivalent to that of Iodine. The results demonstrated that these gold-coated PLGA nanoparticles synthesized by a simple approach could be used as a multifunctional nanosystem for cancer theranostics.

Rational Design of Branched Nanoporous Gold Nanoshells with Enhanced Physico-Optical Properties for Optical Imaging and Cancer Therapy.

Reported procedures on the synthesis of gold nanoshells with smooth surfaces have merely demonstrated efficient control of shell thickness and particle size, yet no branch and nanoporous features on the nanoshell have been implemented to date. Herein, we demonstrate the ability to control the roughness and nanoscale porosity of gold nanoshells by using redox-active polymer poly(vinylphenol)-b-(styrene) nanoparticles as reducing agent and template. The porosity and size of the branches on this branched nanoporous gold nanoshell (BAuNSP) material can be facilely adjusted by control of the reaction speed or the reaction time between the redox-active polymer nanoparticles and gold ions (Au3+). Due to the strong reduction ability of the redox-active polymer, the yield of BAuNSP was virtually 100%. By taking advantage of the sharp branches and nanoporous features, BAuNSP exhibited greatly enhanced physico-optical properties, including photothermal effect, surface-enhanced Raman scattering (SERS), and photoacoustic (PA) signals. The photothermal conversion efficiency can reach as high as 75.5%, which is greater than most gold nanocrystals. Furthermore, the nanoporous nature of the shells allows for effective drug loading and controlled drug release. The thermoresponsive polymer coated on the BAuNSP surface serves as a gate keeper, governing the drug release behavior through photothermal heating. Positron emission tomography imaging demonstrated a high passive tumor accumulation of 64Cu-labeled BAuNSP. The strong SERS signal generated by the SERS-active BAuNSP in vivo, accompanied by enhanced PA signals in the tumor region, provide significant tumor information, including size, morphology, position, and boundaries between tumor and healthy tissues. In vivo tumor therapy experiments demonstrated a highly synergistic chemo-photothermal therapy effect of drug-loaded BAuNSPs, guided by three modes of optical imaging.

Gold nanoshell-based betulinic acid liposomes for synergistic chemo-photothermal therapy.

A novel synthesis approach is first developed to fabricate a multifunctional smart nanodrug delivery system: gold nanoshell-coated betulinic acid liposomes (AuNS-BA-Lips) mediated by a glutathione. The AuNS-BA-Lips exhibited good size distribution (149.4±2.4nm), preferable photothermal conversion ability and synergistic chemo-photothermal therapy. Additionally, the absorption wavelength of AuNS-BA-Lips showed a significantly red-shifted to near infrared (NIR) region, which can strongly absorbed NIR laser and efficiently convert it into localized heat, thus providing controlled drug release and antitumor thermotherapy. Moreover, the nanocarriers excited by NIR light significantly promoted cell uptake compared to those without irradiation, resulting in an enhanced intracellular drug accumulation. Upon NIR irradiation, the AuNS-BA-Lips showed highly efficient antitumor effects on tumor-bearing mice with an inhibition rate of 83.02%, thus demonstrating a remarkable synergistic therapeutic effect of chemotherapy and thermotherapy. Therefore, this work provides new insight into developing a multifunctional antitumor drug.

New Perspectives in Glioblastoma: Nanoparticles-based Approaches.

Glioblastoma multiforme represents one of the most aggressive tumor of central nervous system. Current therapy includes surgery, radiation and chemotherapy. These treatments are rarely curative and glioma are associated with a poor prognosis. Nanomedicine represents the most innovative branch of medicine since many studies demonstrated great advantage in the diagnosis and therapy of several diseases. In this review we will summarize the results obtained by the use of nanoparticles and extracellular vesicles in glioblastoma. A great interest is raising from these studies that underlined the efficacy and specificity of this treatment for glioma, reducing side-effects associated with conventional therapies.

Numerical investigation of thermal response of laser-irradiated biological tissue phantoms embedded with gold nanoshells.

The work presented in this paper focuses on numerically investigating the thermal response of gold nanoshells-embedded biological tissue phantoms with potential applications into photo-thermal therapy wherein the interest is in destroying the cancerous cells with minimum damage to the surrounding healthy cells. The tissue phantom has been irradiated with a pico-second laser. Radiative transfer equation (RTE) has been employed to model the light-tissue interaction using discrete ordinate method (DOM). For determining the temperature distribution inside the tissue phantom, the RTE has been solved in combination with a generalized non-Fourier heat conduction model namely the dual phase lag bio-heat transfer model. The numerical code comprising the coupled RTE-bio-heat transfer equation, developed as a part of the current work, has been benchmarked against the experimental as well as the numerical results available in the literature. It has been demonstrated that the temperature of the optical inhomogeneity inside the biological tissue phantom embedded with gold nanoshells is relatively higher than that of the baseline case (no nanoshells) for the same laser power and operation time. The study clearly underlines the impact of nanoshell concentration and its size on the thermal response of the biological tissue sample. The comparative study concerned with the size and concentration of nanoshells showed that 60nm nanoshells with concentration of 5×1015mm-3 result into the temperature levels that are optimum for the irreversible destruction of cancer infected cells in the context of photo-thermal therapy. To the best of the knowledge of the authors, the present study is one of the first attempts to quantify the influence of gold nanoshells on the temperature distributions inside the biological tissue phantoms upon laser irradiation using the dual phase lag heat conduction model.