PEGylated Gold Nanorods Research Articles

490 A CTS team approach to Gold Nanorod (GNR) Theranostics in Adoptive Cell Therapy (ACT)

OBJECTIVES/GOALS: The objective ofthis study is to use GNR technology to track immune cells infiltrating malignant brain tumors that are delivered as part of a novel immunotherapeutic strategy. We seek to implement this new platform to elucidate the underlying mechanisms of therapeutic benefit from ACT via correlation between biodistribution and efficacy. METHODS/STUDY POPULATION: Utilizing the inherent two-photon luminescent signal of GNRs, we will identify uptake and phenotype of lineage negative hematopoietic stem cells (HSCs) in vitro. HSCs will be isolated from the bone marrow of 6-week-old C57bl/6 female mice. Following isolation, HSCs will be co-cultured with varying concentrations of GNRs in DMEM w/o sodium pyruvate for 24 hours, tested for viability, and images to quantify uptake and identify phenotyping. CT contrast of our novel Iodine-capped PEGylated gold nanorods will be confirmed through microCT and biodistribution of HSCs at time points after injection will be identified via CT visualizationin vivo. RESULTS/ANTICIPATED RESULTS: We expect that increased GNR signaling 24 hours post-transplant in the tumors of glioma-bearing mice will be positively correlated with long term survival following ACT. Published data from our labs have revealed that CCR2+ lineage-negative HSCs significantly accumulate in tumor of glioma-bearing mice12. Importantly, CCR2+ lineage-negative HSCs promote differentiation to dendritic cells in the tumor, increase antitumor T cell responses mediated by cross-priming and cross-presentation, and improve efficacy of immune checkpoint inhibition12. Given that HSCs are important in mediating immunotherapy efficacy, we seek to correlate the accumulation of GNR signaling within the tumor as a marker of treatment response. DISCUSSION/SIGNIFICANCE: Adoptively transferred cells have been imaged using numerous published methods. While promising to the field of immunotherapy, these methods lack significant clinical validation. GNRs have not been used to study hematopoietic stem cells in the context of ACT and brain malignancies. Our research is poised to address this gap.

Radiotherapy Metastatic Prostate Cancer Cell Lines Treated with Gold Nanorods Modulate miRNA Signatures.

MicroRNA (miRNA) modulation has been identified as a promising strategy for improving the response of human prostate cancer (PCa) to radiotherapy (RT). Studies have shown that mimics or inhibitors of miRNAs could modulate the sensitivity of PCa cells to RT. In addition, pegylated gold nanoparticles have been studied as a therapeutic approach to treat PCa cells and/or vehicles for carrying miRNAs to the inside of cells. Therefore, we evaluated the capacity of hypofractionated RT and pegylated gold nanorods (AuNPr-PEG) to modulate the miRNA signature on PCa cells. Thus, RT-qPCR was used to analyze miRNA-95, miRNA-106-5p, miRNA-145-5p, and miRNA-541-3p on three human metastatic prostate cell lines (PC3, DU145, and LNCaP) and one human prostate epithelial cell line (HprEpiC, a non-tumor cell line) with and without treatment. Our results showed that miRNA expression levels depend on cell type and the treatment combination applied using RT and AuNPr-PEG. In addition, cells pre-treated with AuNPr-PEG and submitted to 2.5 Gy per day for 3 days decreased the expression levels of miRNA-95, miRNA-106, miRNA-145, and miRNA-541-3p. In conclusion, PCa patients submitted to hypofractionated RT could receive personalized treatment based on their metastatic cellular miRNA signature, and AuNPr-PEG could be used to increase metastatic cell radiosensitivity.

Near-Infrared Remotely Controllable Shape Memory Biodegradable Occluder Based on Poly(l-lactide-co-ε-caprolactone)/Gold Nanorod Composite.

Biodegradable occluders, which can efficiently eliminate the complications caused by permanent foreign implants, are considered to be the next-generation devices for the interventional treatment of congenital heart disease. However, the controllability of the deployment process of degradable occluders remains a challenge. In this work, a near-infrared (NIR) remotely controllable biodegradable occluder is explored by integrating poly(l-lactide-co-ε-caprolactone) (PLCL) with poly(ethylene glycol)-modified gold nanorods (GNR/PEG). The caprolactone structural units can effectively increase the toughness of poly(l-lactide) and reduce the shape-memory transition temperature of the occluder to a more tissue-friendly temperature. Gold nanorods endow the PLCL-GNR/PEG composite with an excellent photothermal effect. The obtained occluder can be easily loaded into a catheter for transport and spatiotemporally expanded under irradiation with near-infrared light to block the defect site. Both in vitro and in vivo biological experiments showed that PLCL-GNR/PEG composites have good biocompatibility, and the PEGylated gold nanorods could improve the hemocompatibility of the composites to a certain extent by enhancing their hydrophilicity. As a thermoplastic shape-memory polymer, PLCL-GNR/PEG can be easily processed into various forms and structures for different patients and lesions. Therefore, PLCL-GNR/PEG has the potential to be considered as a competitive biodegradable material not only for occluders but also for other biodegradable implants.

A simple and robust nanosystem for photoacoustic imaging of bladder cancer based on α5β1-targeted gold nanorods

BackgroundEarly detection and removal of bladder cancer in patients is crucial to prevent tumor recurrence and progression. Because current imaging techniques may fail to detect small lesions of in situ carcinomas, patients with bladder cancer often relapse after initial diagnosis, thereby requiring frequent follow-up and treatments.ResultsIn an attempt to obtain a sensitive and high-resolution imaging modality for bladder cancer, we have developed a photoacoustic imaging approach based on the use of PEGylated gold nanorods (GNRs) as a contrast agent, functionalized with the peptide cyclic [CphgisoDGRG] (Iso4), a selective ligand of α5β1 integrin expressed by bladder cancer cells. This product (called GNRs@PEG-Iso4) was produced by a simple two-step procedure based on GNRs activation with lipoic acid-polyethyleneglycol(PEG-5KDa)-maleimide and functionalization with peptide Iso4. Biochemical and biological studies showed that GNRs@PEG-Iso4 can efficiently recognize purified integrin α5β1 and α5β1-positive bladder cancer cells. GNRs@PEG-Iso4 was stable and did not aggregate in urine or in 5% sodium chloride, or after freeze/thaw cycles or prolonged exposure to 55 °C, and, even more importantly, do not settle after instillation into the bladder. Intravesical instillation of GNRs@PEG-Iso4 into mice bearing orthotopic MB49-Luc bladder tumors, followed by photoacoustic imaging, efficiently detected small cancer lesions. The binding to tumor lesions was competed by a neutralizing anti-α5β1 integrin antibody; furthermore, no binding was observed to healthy bladders (α5β1-negative), pointing to a specific targeting mechanism.ConclusionGNRs@PEG-Iso4 represents a simple and robust contrast agent for photoacoustic imaging and diagnosis of small bladder cancer lesions.Graphical

Effect of PEGylated gold nanorods on the circulating vascular endothelial growth factor, platelet-derived growth factor, and miR-29a in CD-1 mice

The Journal of the National Science Foundation of Sri Lanka publishes the results of research in all aspects of Science and Technology. The journal also has a website at http://www.nsf.gov.lk/. 2021 Impact Factor: 0.682The JNSF provides immediate open access to its content on the principle that making research freely available to the public supports a greater global exchange of knowledge.

Pathways Related to NLRP3 Inflammasome Activation Induced by Gold Nanorods.

The widespread and increasing use of engineered nanomaterials (ENM) increases the risk of human exposure, generating concern that ENM may provoke adverse health effects. In this respect, their physicochemical characteristics are critical. The immune system may respond to ENM through inflammatory reactions. The NLRP3 inflammasome responds to a wide range of ENM, and its activation is associated with various inflammatory diseases. Recently, anisotropic ENM have become of increasing interest, but knowledge of their effects on the immune system is still limited. The objective of the study was to compare the effects of gold ENM of different shapes on NLRP3 inflammasome activation and related signalling pathways. Differentiated THP-1 cells (wildtype, ASC- or NLRP3-deficient), were exposed to PEGylated gold nanorods, nanostars, and nanospheres, and, thus, also different surface chemistries, to assess NLRP3 inflammasome activation. Next, the exposed cells were subjected to gene expression analysis. Nanorods, but not nanostars or nanospheres, showed NLRP3 inflammasome activation. ASC- or NLRP3-deficient cells did not show this effect. Gene Set Enrichment Analysis revealed that gold nanorod-induced NLRP3 inflammasome activation was accompanied by downregulated sterol/cholesterol biosynthesis, oxidative phosphorylation, and purinergic receptor signalling. At the level of individual genes, downregulation of Paraoxonase-2, a protein that controls oxidative stress, was most notable. In conclusion, the shape and surface chemistry of gold nanoparticles determine NLRP3 inflammasome activation. Future studies should include particle uptake and intracellular localization.

Optimizing SERS performance through aggregation of gold nanorods in Langmuir-Blodgett films

Nanoparticles with a high degree of anisotropy are characterized by large electromagnetic field enhancements at the single-particle level; however, their arrangement into aggregated structures does not lead to significantly better performance. Surprisingly, for nanorods a superior accumulation of hot spots is present at surface coverages above 60%, which ensures a higher efficiency for surface-enhanced Raman spectroscopy (SERS). In this study, we produced pegylated gold nanorods in Langmuir-Blodgett layers in order to optimize SERS performance for the ultrasensitive detection of molecules, by tuning plasmonic coupling and nanoparticle surface coverage. To understand the arrangement of the nanorods in Langmuir and Langmuir-Blodgett layers, we performed spectroscopic and microscopic analysis of the obtained films. Based on the compression isotherms of the nanorods, we proposed the best conditions for nanoplatform design. The Raman enhancement factor was around 2·105 with a deposition surface pressure equal to 12 mN·m−1. Due to the polymer’s presence at the surface of the nanorods and the dewetting process, specific dendritic-like aggregates were observed on the solid substrate. The results obtained indicate the significance of further studies on the arrangement of metallic nanoparticles in monolayers, taking into account the size and shape of the nanoparticles, as well as the type of stabilizing ligands at their surface.

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.

Photothermal Transfection for Effective Nonviral Genome Editing.

The efficient nonviral delivery of nucleic acids into the cytoplasm is needed to fully realize the potential of gene therapy. Although cationic lipids and nanoparticles have been widely used to improve the intracellular delivery of nucleic acids, they suffer from cytotoxicity and poor endosomal escape, thus limiting the transfection efficacy. Here, we developed a photothermal transfection platform for efficient and biosafe intracellular delivery of nucleic acids. Photothermal transfection was carried out by irradiation of cells co-treated with Lipofectamine-plasmid DNA complexes and PEGylated gold nanorods (GNRs) using an NIR laser for 30 min and subsequent incubation of the cells for 30 min without laser irradiation. Compared to conventional Lipofectamine-based transfection, our photothermal transfection platform significantly improved the transfection efficiency in difficult-to-transfect human primary cells including human dermal fibroblasts while maintaining the cell viability. The photothermal heating did not leave the GNRs inside the cell, thereby minimizing the cellular damage. Furthermore, the photothermal transfection platform showed superior genome editing abilities (both gene cleavage and insertion) in human dermal fibroblasts than conventional Lipofectamine-based transfection.

Controlled Synthesis and Surface Engineering of Janus Chitosan‐Gold Nanoparticles for Photoacoustic Imaging‐Guided Synergistic Gene/Photothermal Therapy

The unsymmetrical morphology and unique properties of Janus nanoparticles (JNPs) provide superior performances for biomedical applications. In this work, a general and facile strategy is developed to construct a series of symmetrical and unsymmetrical chitosan/gold nanoparticles. Taking advantage of the active motion derived from Janus structure, selective surface functionalization of polysaccharide domain, and photothermal effect of gold nanorods, Janus chitosan/gold nanoparticles (J-Au-CS) are selected as a model system to construct Janus-structured chitosan/gold nanohybrids (J-ACP). Near-infrared (NIR)-responsive J-ACP composed of polycationic chitosan nanospheres and PEGylated gold nanorods hold great potential to realize photoacoustic (PA) imaging-guided complementary photothermal therapy (PTT)/gene therapy for breast cancer. The morphology effect of chitosan/gold nanostructures on enhanced PTT, cellular uptake, and gene transfection is investigated. The feasibility of PA imaging to track the accumulation of J-ACP and guide PTT is also explored. Notably, synergistic therapy is achieved based on PTT-enhanced gene therapy. In addition, the loading function of chitosan/gold nanoparticles for fluorescence imaging is demonstrated. The current work extends the application of JNPs for imaging-guided synergistic cancer therapy and provides flexible candidates with distinct structures for diverse biomedical applications.

Cytotoxicity and genotoxicity of gold nanorods assisted photothermal therapy against Ehrlich carcinoma in-vivo

AimPreparation of pegylated gold nanorods (PEG-AuNRs) that are capable of converting near infrared (NIR) light into heat. Evaluation of cancer therapeutic efficacy and long-term toxicity of the proposed photothermal therapy in comparison with other conventional modalities. Materials and methodsPrepared PEG-AuNRs were characterized by measuring their absorption spectra, zeta potential, and transmission electron microscope (TEM). Cancer therapeutic efficacy was assessed by monitoring tumor growth, measuring DNA damage and superoxide dismutase (SOD) and malondialdehyde (MDA) levels in addition to examining tumor histopathology. Further analysis concerning the toxicity of all the proposed treatment modalities was also assessed by evaluating the cytotoxicity and genotoxicity in liver and kidney tissues. Key findingsThe results demonstrated that both photothermal therapy (PEG-AuNRs + NIR laser) and chemotherapy (cisplatin) have higher efficacy in diminishing Ehrlich tumor growth with significance DNA damage over the other treatment modalities.Concerning the biosafety issue, mice treated photothermally exhibited lower MDA level and higher SOD activity in liver and kidney tissues compared with other treated groups. DNA damage represented by tail moment and olive moment of kidney tissues exhibited lower values for photothermal treated group and higher values for cisplatin treated group. SignificancePhotothermal therapy (PEG-AuNRs + NIR laser) potentiates higher efficacy in treating Ehrlich tumor with minimum toxicity in comparison with other conventional treatment modalities.

PEGylated gold nanorods with a broad absorption band in the first near-infrared window for in vivo multifunctional photoacoustic imaging.

Nanoparticles with absorbances in the near-infrared window (NIR, 700–1300 nm) are ideal contrast agents for in vivo imaging of deep tissue with high signal-to-noise ratios. By using CTAB and l(+)-ascorbic acid (AA) as ligands to effectively balance particle nucleation and growth, PEGylated Au nanorods (NRs) with broad absorption bands (from 650 to 1100 nm) in the first NIR window could be successfully realized. The morphologies, crystal structures, absorption and biotoxicities of the samples were determined by TEM, TGA, UV-vis and MTT assay. The results indicated that the presence of a thin poly(ethylene glycol) (PEG) shell could greatly improve the biocompatibility of the Au NRs (1.7 times that of non-PEGylated Au NRs), making them harmless to living cells. Moreover, the prepared PEGylated Au NRs displayed the highest image contrast and SNR values (1.1–1.5 times that of commercial Au nanospheres and NRs), with excitation lasers of 532, 680 and 828 nm, showing their great potential for use in multicolor photoacoustic imaging in vivo. With the prepared PEGylated Au NRs, a functional image of oxygen saturation was constructed in a single step without changing the contrast agent.

Supercrystal Formation of Gold Nanorods by High Pressure Stimulation

We demonstrate the pressure-induced formation of supercrystals made from PEGylated gold nanorods (NRs) in aqueous suspension. Utilizing the combined effect of hydrostatic pressure and salt on the solubility of the organic poly(ethylene glycol) (PEG) shell that passivates the NRs, the reversible formation of two-dimensional hexagonal supercrystals has been observed by means of small-angle X-ray scattering. The pressure dependence of the crystal lattice’s structural parameters is determined. By time-resolved measurements performed after a pressure jump, the growth process of the crystals is found to be completed already after a few seconds. The presented results demonstrate that by PEGylating nanoparticles, pressure-induced homogeneous supercrystals can be formed for different particle shapes, in particular, anisotropic NRs, which determine the resulting lattice type.

PEGylated gold nanorods are not cytotoxic to human endothelial cells but affect kruppel-like factor signaling pathway

Gold (Au) nanomaterials (NMs), particularly those with PEG surface functionalization, are generally considered to be biocompatible for biomedical applications due to relatively low cytotoxicity. Herein, we investigated the toxicity of PEGylated Au nanorods (NRs) to human umbilical vein endothelial cells (HUVECs), a commonly used in vitro model for human endothelium. We found a previously unknown effect that up to 10 μg/mL Au NRs, albeit not cytotoxic, decreased the mRNA and protein levels of kruppel-like factor 2 (KLF2), a transcription factor with well-documented vasoprotective effects. The results from PCR array showed that a number of genes associated with risk of cardiovascular diseases were altered by Au NRs, and several genes are downstream genes of KLF2 according to ingenuity pathway analysis (IPA). These effects could be observed with or without the presence of inflammatory stimuli lipopolysaccharide (LPS), which suggests a pre-existing inflammatory state is not required for Au NRs to alter KLF2 signaling pathway. We further identified that Au NRs significantly decreased eNOS mRNA/p-eNOS proteins as well as increased MCP-1 mRNA/sMCP-1 release, which are targets of KLF2. Combined, our data revealed a novel pathway that PEGylated Au NPs at non-cytotoxic concentrations might alter KLF leading to the increase of risk of cardiovascular diseases in human endothelial cells. Given the importance of KLF in vascular homeostasis, our data indicate that it is necessary to evaluate the influence of engineered NPs to KLF signaling pathways, especially for NPs with biomedical uses.

DNA Damage in Ehrlich Carcinoma induced by Gold Nanorods Mediated Photothermal Therapy

Gold nanorods (AuNRs) are promising nanoplatforms for cancer photothermal therapy due to their capability to absorb light in the near-infrared (NIR) window. This work was conducted to evaluate the DNA damage in Ehrlich tumor tissues associated with photothermal therapy mediated with very small sized pegylated gold nanorods (PEG-AuNRs). The accumulated gold nanorods inside tumor tissues were photo-excited with 300 mW NIR laser for 50 min. The physical properties of PEG-AuNRs were investigated using transmission electron microscopy, size distribution measurement, and UV-vis absorption spectroscopy. The efficacy of the in-vivo photothermal therapy of intravenously injected PEG-AuNRs was assessed using tumor size measurements. Also, oxidative stress and comet assay were performed to measure the percentage of DNA damage. The results showed that PEG-AuNRs were successfully prepared with a length of 8 nm and a longitudinal absorption peak at 800 nm. FTIR study confirmed the successful coating of polyethylene glycol on the surface of the gold nanorods. The in vivo experiment showed that PEG-AuNRs elicited tumoral growth arrest by producing free radicals in addition to its photo heat conversion which was sufficient to induce cellular damage by causing DNA damage

Photothermal effects on protein adsorption dynamics of PEGylated gold nanorods

The effect of thermoplasmonic heating on the dynamics of the protein corona around polyethylene glycol (PEG) coated gold nanorods (GNRs) is reported. GNRs were surface-modified with densely packed shells composed of thiolated PEGs bearing carboxyl and/or amine end-terminal groups, which led to negatively, positively or neutral charged GNRs. The three types of PEGylated GNRs, although with subtle differences among them, present weak interactions (binding dissociation constants in the μM range) with the model protein bovine serum albumin (BSA), as determined by different methods including gel electrophoresis, laser Doppler anemometry and isothermal titration calorimetry (ITC). In general, plasmonic photothermal heating significantly changed the composition of the protein corona around GRNs, particularly, on the positively charged ones. Moreover, a pre-formed BSA corona on the PEGylated GNRs further decreased their already reduced uptake by cells. However, photothermal treatment of BSA-coated GNRs only produced a significant decreased internalization in the case of non-PEGylated control samples. Overall, our results indicate that differently surface charged PEGylations on GNRs affects the dynamics of protein corona formation, which is particularly relevant after photothermal treatment. Such effects are nonetheless non-significant concerning cellular uptake.

Photoacoustic molecular imaging using combined acupuncture and gold nanorods as a composite contrast agent

In this study, we developed a novel photoacoustic imaging technique based on poly (ethyleneglycol)-coated (PEGylated) gold nanorods (PEG-GNRs) (as the contrast agent) combined with traditional Chinese medicine (TCM) acupuncture (as the auxiliary method) for quantitatively monitoring contrast enhancement in the vasculature of a mouse brain in vivo. This study takes advantage of the strong near-infrared absorption (peak at [Formula: see text][Formula: see text]nm) of GNRs and the ability to adjust the hemodynamics of acupuncture. Experimental results show that photoacoustic tomography (PAT) successfully reveals the optical absorption variation of the vasculature of the mouse brain in response to intravenous administration of GNRs and acupuncture at the Zusanli acupoint (ST36) both individually and combined. The quantitative measurement of contrast enhancement indicates that the composite contrast agents (integration of acupuncture and GNRs) would greatly enhance the photoacoustic imaging contrast. The quantitative results also have the potential to estimate the local concentration of GNRs and even the real-time effects of acupuncture.

Development of anisamide-targeted PEGylated gold nanorods to deliver epirubicin for chemo-photothermal therapy in tumor-bearing mice.

BackgroundGold nanorods (AuNRs), due to the optical and electronic properties namely the surface plasma resonance, have been developed to achieve the light-mediated photothermal therapy (PTT) for cancer. However, PTT alone may suffer from inefficient tumor killing. Recently, the combination of PTT and chemotherapy has been utilized to achieve synergistic anticancer effects.MethodsIn this study, AuNRs capped with hexadecyltrimethylammonium bromide (CTAB), poly(acrylic acid) (PAA), and PEGylated anisamide (a ligand known to target the sigma receptor) have been developed to produce a range of negatively charged anisamide-targeted PEGylated AuNRs (namely Au-CTAB-PAA-PEG-AA) for the combination of PTT and chemotherapy (termed as chemo-photothermal therapy [CPTT]). Epirubicin (EPI, an anthracycline drug) was efficiently loaded onto the surface of Au800-CTAB-PAA-PEG-AA via the electrostatic interaction forming Au800-CTAB-PAA-PEG-AA.EPI complex.ResultsThe resultant complex demonstrated pH-dependent drug release, facilitated nucleus trafficking of EPI, and induced antiproliferative effects in human prostate cancer PC-3 cells. When Au800-CTAB-PAA-PEG-AA.EPI complex was further stimulated with desired laser irradiation, the synergistic outcome was evident in PC-3 xenograft mice.ConclusionThese results demonstrate a promising strategy for clinical application of CPTT in cancer.

Confined growth of multiple gold nanorices in dual-mesoporous silica nanospheres for improved computed tomography imaging and photothermal therapy.

IntroductionIn this work, we have developed a novel “confined-growth” strategy to synthesize PEGylated multiple gold nanorices-encapsulated dual-mesoporous silica nanospheres (designated as PEGylated MGNRs@DMSSs) containing both small mesopores (2.5 nm) in the shell and large mesopores (21.7 nm) in the core based on a well-established, seed-mediated growth method. The photothermal effect and CT imaging ability were also studied.MethodsThe nanoparticles were characterized by Fourier transform infrared (FT-IR) spectra, N2 absorption isotherms, Field-emission scanning electron microscopy (FE-SEM), Transmission electron microscopy (TEM), Inductively coupled plasma atomic emission spectroscopy (ICP-AES) and Confocal microscopy.ResultsThe longitudinally-localized surface (LSPR) absorption properties of MGNRs@DMSSs can be easily tuned by altering the amount of HAuCl4 in the gold growth solution. Additionally, the resultant PEGylated MGNRs@DMSSs have monodispersed, spherical morphology and good colloidal stability in an aqueous solution. More importantly, when exposed to NIR irradiation, the PEGylated MGNRs@DMSSs exhibit both higher temperature increments and better photothermal effects than that of single PEGylated gold nanorods at nearly an equivalent LSPR absorption. In addition, as CT contrast agents, the PEGylated MGNRs@DMSSs display a better CT imaging performance, in comparison with single PEGylated gold nanorods at the same Au concentration.ConclusionTaken together, results indicate the potential for MGNRs@DMSSs used in CT imaging-guided photothermal therapy. Such a simple “confined-growth” strategy within a porous matrix offers a promising platform to design and prepare novel metal(s) oxide@silica nanocomposites for use in further cancer bio-imaging and therapy.

Transforming Weakness into Strength: Photothermal-Therapy-Induced Inflammation Enhanced Cytopharmaceutical Chemotherapy as a Combination Anticancer Treatment.

A new synergistic treatment that combines photothermal therapy (PTT) and inflammation-mediated active targeting (IMAT) chemotherapy based on cytopharmaceuticals is developed. During PTT, the photothermal tumor ablation is accompanied by an inflammatory effect and upregulation of inflammatory factors at the tumor site, which may accelerate tumor regeneration. Moreover, PTT-induced inflammation can also recruit neutrophils (NEs) to the tumor site. To convert the disadvantages of PTT-induced inflammation into strengths, NEs are investigated as cytopharmaceuticals for IMAT chemotherapy to further inhibit the tumor recurrence after PTT due to the chemotaxis of NEs to the inflammatory sites. In this study, PEGylated gold nanorods (PEG-GNRs) are explored as the photothermal agent and paclitaxel-loaded cytopharmaceuticals of NEs as the IMAT chemotherapeutic agent. PTT is conducted at 72 h postinjection of PEG-GNRs, followed by cytopharmaceuticals for IMAT chemotherapy. It is demonstrated that the cytopharmaceuticals effectively accumulate in the tumor sites after PTT, which leads to a significant enhancement of antitumor efficacy and a reduction in systemic toxicity. These studies suggest that PTT-induced inflammation further enhances the chemotherapy of cytopharmaceuticals, and the combination of PTT and IMAT chemotherapy may be a promising synergistic strategy for targeted cancer therapy.