Biogenic Cluster-Encased Gold Nanorods as a Targeted Three-in-One Theranostic Nanoenvelope for SERS-Guided Photochemotherapy against Metastatic Melanoma (original) (raw)
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Targeted Chemo-Photothermal Therapy: A Nanomedicine Approximation to Selective Melanoma Treatment
Particle & Particle Systems Characterization, 2018
Melanoma is one of the most severe public health issues worldwide, not only because of the high number of cases but also for its poor prognosis in late stages. Therefore, early diagnosis and efficient treatment are key toward a future solution. However, melanoma is highly resistant to cytotoxicity in its metastatic form. In this context, a therapeutic strategy based on a targeted chemo-photothermal nanotransporter for cytotoxic compounds is proposed. This approach comprises the use of core–multishell gold nanorods, coated with mesoporous silica and further covered with a thermosensitive polymer, which is vectorized for selective internalization in melanoma cells. Theproposed nanoformulation is capable of releasing the transported cytotoxic compounds on demand, in response to near-IR irradiation, with high selectivity and efficacy against malignant cells, even at low concentrations, thereby providing a new tool against melanoma disease.
Journal of Nanomaterials, 2014
Photothermal therapy (PTT) treatments have shown strong potential in treating tumors through their ability to target destructive heat preferentially to tumor regions. In this paper we demonstrate that PTT in a murine melanoma model using gold nanorods (GNRs) and near-infrared (NIR) light decreases tumor volume and increases animal survival to an extent that is comparable to the current generation of melanoma drugs. GNRs, in particular, have shown a strong ability to reach ablative temperatures quickly in tumors when exposed to NIR light. The current research tests the efficacy of GNRs PTT in a difficult and fast growing murine melanoma model using a NIR light-emitting diode (LED) light source. LED light sources in the NIR spectrum could provide a safer and more practical approach to photothermal therapy than lasers. We also show that the LED light source can effectively and quickly heat in vitro and in vivo models to ablative temperatures when combined with GNRs. We anticipate that this approach could have significant implications for human cancer therapy.
Materials Science and Engineering: C, 2018
The chemo-photothermal therapy performance of a novel theranostic nanoparticles that fabricated through the conjugation of HS-poly(ε-caprolactone)-block-poly(Nisopropylacrylamide)-block-poly(acrylic acid) (HS-PCL-b-PNIPAAm-b-PAA) and gold nanoparticles (GNPs) was extensively investigated. The GNPs@polymer conjugate theranostic NPs was loaded with doxorubicin hydrochloride (DOX) as an anticancer drug through electrostatic interactions to afford GNPs@polymer-DOX theranostic nanomedicine. Temperature and pH triggered in vitro drug release behavior of the developed theranostic nanomedicine was also examined. The biocompatibility of the synthesized GNPs@polymer theranostic NPs was confirmed through the assessing survival rate of breast cancer cell line (MCF7) using MTT assay. In vitro cytotoxic effects of the GNPs@polymer-DOX theranostic nanomedicine was also evaluated against MCF7 cells in both with or without laser irradiation (532 nm, 145 mJ per pulse, 5 minutes) conditions, and the results obtained were compared with free DOX as the reference. As the results, the developed GNPs@polymer-DOX can be considered as theranostic nanomedicine for chemo-photothermal therapy of solid tumors.
Nanomaterials for photothermal and photodynamic cancer therapy
Applied Physics Reviews, 2022
In recent years, the role of optically sensitive nanomaterials has become powerful moieties in therapeutic techniques and has become particularly emphasized. Currently, by the extraordinary development of nanomaterials in different fields of medicine, they have found new applications. Phototherapy modalities, such as photothermal therapy (PTT) by toxic heat generation and photodynamic therapy (PDT) by reactive oxygen species, are known as promising phototherapeutic techniques, which can overcome the limitations of conventional protocols. Moreover, nanomaterial-based PDT and PTT match the simultaneous immune therapy and increase the immune system stimulation resulting from the denaturation of cancer cells. Nevertheless, nanomaterials should have sufficient biocompatibility and efficiency to meet PDT and PTT requirements as therapeutic agents. The present review focuses on the therapeutic potency of PDT, PTT, and also their combined modalities, which are known alternative protocols wi...
2021
Photodynamic therapy (PDT) and photothermal therapy (PTT) are promising therapeutic methods for cancer treatment; however, as single modality therapies, either PDT or PTT are still limited in their success rate. A dual application of both PDT and PTT, in a combined protocol, has gained immense interest. In this study, gold nanoparticles (AuNPs) are conjugated with a PDT agent, meso-tetrahydroxyphenylchlorin (mTHPC) photosensitizer, designed as nanotherapeutic agents that can activate a dual photodynamic/photothermal therapy. The AuNP-mTHPC complex is biocompatible, soluable, and photostable. PDT efficiency is high because of immediate reactive oxygen species (ROS) production upon mTHPC activation by the 650 nm laser which decreased mitochondrial membrane potential (∆ψm). Likewise, the AuNP-mTHPC complex is used as a photoabsorbing (PTA) agent for PTT, due to efficient plasmon absorption and excellent photothermal conversion characteristics of AuNPs under laser irradiation at 532 nm....
Acta Biomaterialia, 2019
The poor delivery of nanoparticles to target cancer cells hinders their success in the clinical setting. In this work, an alternative target readily available for circulating nanoparticles has been selected to eliminate the need for nanoparticle penetration in the tissue: the tumor blood vessels. A tumor endothelium-targeted nanoparticle (employing an RGD-containing peptide) capable of co-delivering two anti-vascular drugs (one anti-angiogenic drug and one vascular disruption agent) is here presented. Furthermore, the nanodevice presents two additional anti-vascular capabilities upon activation by Near-Infrared light: provoking local hyperthermia (by gold nanorods in the system) and generating toxic reactive oxygen species (by the presence of a photosensitizer). RGD-targeting is shown to increase uptake by HUVEC cells, and while the nanoparticles are shown not to be toxic for these cells, upon Near-Infrared irradiation their almost complete killing is achieved. The combination of all four therapeutic modalities is then evaluated in an ex ovo fibrosarcoma xenograft model, which shows a significant reduction in the number of blood vessels irrigating the xenografts when the nanoparticles are present, as well as the destruction of the existing blood vessels upon irradiation. These results suggest that the combination of different anti-vascular therapeutic strategies in a single nanocarrier appears promising and should be further explored in the future. Statement of significance MVR2019 The combination of antivascular drugs with different mechanisms of action (such as antiangiogenic drugs and vascular disruption agents) has been recently proposed as a promising approach to maximize the therapeutic potential of anti-vascular therapeutics. Given the capacity of nanoparticles to co-deliver different drugs in optimizable ratios, nanomedicine appears to have a huge potential for the development of this kind of multimodal antivascular. To showcase this, an multimodal anti-vascular nanode-vice for cancer therapy is here presented. This tumor endothelium-targeted nanosystem is capable of co-delivering two anti-vascular drugs (anti-angiogenic and vascular disruption agent) while also providing two additional therapeutic modalities that can be activated by Near-Infrared light: provoking local hyperthermia (photothermal therapy) and generating toxic reactive oxygen species (photodynamic therapy).
Mediterranean Journal of Chemistry
The advanced skin cancer melanoma, which is primarily caused by the mutation of BRAF gene, has a high mortality rate and requires high doses of chemotherapeutic drugs. To mitigate the drug toxicity to healthy cells and other side effects, the development of alternative modes of treatment has been extensively sought after. Herein, we describe a new targeted drug delivery system with controlled release, based on nanoparticle nanocarriers functionalized with folate and transferrin ligands for recognition of the respective receptors overexpressed in cancer cell membrane. We have investigated the immobilization of a new drug dabrafenib onto the nanocarriers and its controlled release, aided with surface-enhanced Raman scattering (SERS) spectroscopy which affords ultra-sensitive in situ measurement ability owing to the high signal amplification, associated with strong plasmonic fields of the nanocarrier gold nanoparticle (AuNP) cores. The nanocarriers were equipped with Raman reporters: m...
Photothermal nanodrugs: potential of TNF-gold nanospheres for cancer theranostics
Scientific Reports, 2013
Nanotechnology has been extensively explored for drug delivery. Here, we introduce the concept of a nanodrug based on synergy of photothermally-activated physical and biological effects in nanoparticle-drug conjugates. To prove this concept, we utilized tumor necrosis factor-alpha coated gold nanospheres (Au-TNF) heated by laser pulses. To enhance photothermal efficiency in near-infrared window of tissue transparency we explored slightly ellipsoidal nanoparticles, its clustering, and laser-induced nonlinear dynamic phenomena leading to amplification and spectral sharpening of photothermal and photoacoustic resonances red-shifted relatively to linear plasmonic resonances. Using a murine carcinoma model, we demonstrated higher therapy efficacy of Au-TNF conjugates compared to laser and Au-TNF alone or laser with TNF-free gold nanospheres. The photothermal activation of low toxicity Au-TNF conjugates, which are in phase II trials in humans, with a laser approved for medical applications opens new avenues in the development of clinically relevant nanodrugs with synergistic antitumor theranostic action. V arious nanoparticles have been extensively explored either as imaging contrast agents or as a transformer of various energy modalities (e.g., laser, ultrasound, and radio-waves) to thermal and accompanied phenomena (e.g., nanobubbles, acoustic and shock waves, or nanoparticle explosion) responsible for therapeutic effects or as vehicles for drug delivery 1-11 . In particular, laser-induced photothermal (PT) effects in targeted cells lead to protein denaturation, mechanical membrane damage, and even cell fragmentation . PT effects can also provide controllable drug release from nano-carriers followed by conventional biochemical drug action 11 . However, little progress has been made in the use of nanotechnology to directly activate and/or amplify biochemical drug action.
Oncotarget, 2014
In the photothermal treatments (PTs) of tumor, the localization of a high number of near-infrared (NIR) absorbing gold nanoparticles in the tumor mass is still a challenging issue. Here, we propose a promising strategy to deliver therapeutic chitosan-coated gold nanoparticles to tumor cells as hidden cargo of Endothelial Colony Forming Cells (ECFCs) endowed with an innate tumor-tropism. Remarkably, ECFC gold enrichement doesn't affect cell viability and preserves the endothelial lineage characteristics such as capillary morphogenesis and cell migration. We demonstrate that heavily Au-doped ECFCs are able to efficiently warm up the tumor environment, and kill the cancer cells via hyperthermic heating both in vitro as well as in vivo. Thus, we show an excellent thermotransductive property of gold enriched ECFCs and their capability to kill melanoma cells at moderate NIR light intensities.
Scientific reports, 2018
Photothermal therapy (PTT) is a promising approach for cancer targeting therapy. However, the temperature-dependent killing of tumor cells in PTT remains unclear. In this study, we report necroptosis plays a role in the anti-tumor effects observed in gold nanorod (GNR)-mediated PTT in melanoma. We first synthesized gold nanorods with a targeting adaptor FA (GNRs-FA), which achieved high efficacy of targeted delivery to melanoma cells. We further demonstrated PTT, precipitated by GNRs-FA under the induction of near-infrared laser, was temperature-dependent. Furthermore, the photothermal killing of melanoma cells showed different patterns of cell death depending on varying temperature in PTT. In a lower temperature at 43 °C, the percentages of apoptosis, necroptosis and necrosis of tumor cells were 10.2%, 18.3%, and 17.6%, respectively, suggesting the cell killing is ineffective at lower temperatures. When the temperature increased to 49 °C, the cell death pattern switched to necrosis...