Gold Nanorods as Drug Delivery Vehicles for Rifampicin Greatly Improve the Efficacy of Combating <i>Mycobacterium tuberculosis</i> with Good Biocompatibility with the Host Cells

Ali, Hala R.; Ali, Moustafa R. K.; Wu, Yue; Selim, Salah A.; Abdelaal, Hazem F. M.; Nasr, Eman; El‐Sayed, Mostafa A.

doi:10.1021/acs.bioconjchem.6b00430

Cited by 47 publications

(29 citation statements)

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“…After PPTT, the RF peaks of the particles (330 nm and 470 nm) disappeared, accompanied by increased concentration of RF in the supernatant, indicating the release of surface RF. The number of RF molecules per AuNRs was calculated according to a previous study (36). From the calculation, we found 657 RF molecules present on each AuNRs@BSA, most of which was released after PPTT as shown in Fig.…”

Section: Efficacy Of Aunr@rf/pptt In Cellular Growth Inhibition In VImentioning

confidence: 99%

Efficacy, long-term toxicity, and mechanistic studies of gold nanorods photothermal therapy of cancer in xenograft mice

Ali

Rahman

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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245

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Gold nanorods (AuNRs)-assisted plasmonic photothermal therapy (AuNRs-PPTT) is a promising strategy for combating cancer in which AuNRs absorb near-infrared light and convert it into heat, causing cell death mainly by apoptosis and/or necrosis. Developing a valid PPTT that induces cancer cell apoptosis and avoids necrosis in vivo and exploring its molecular mechanism of action is of great importance. Furthermore, assessment of the long-term fate of the AuNRs after treatment is critical for clinical use. We first optimized the size, surface modification [rifampicin (RF) conjugation], and concentration (2.5 nM) of AuNRs and the PPTT laser power (2 W/cm) to achieve maximal induction of apoptosis. Second, we studied the potential mechanism of action of AuNRs-PPTT using quantitative proteomic analysis in mouse tumor tissues. Several death pathways were identified, mainly involving apoptosis and cell death by releasing neutrophil extracellular traps (NETs) (NETosis), which were more obvious upon PPTT using RF-conjugated AuNRs (AuNRs@RF) than with polyethylene glycol thiol-conjugated AuNRs. Cytochrome and p53-related apoptosis mechanisms were identified as contributing to the enhanced effect of PPTT with AuNRs@RF. Furthermore, Pin1 and IL18-related signaling contributed to the observed perturbation of the NETosis pathway by PPTT with AuNRs@RF. Third, we report a 15-month toxicity study that showed no long-term toxicity of AuNRs in vivo. Together, these data demonstrate that our AuNRs-PPTT platform is effective and safe for cancer therapy in mouse models. These findings provide a strong framework for the translation of PPTT to the clinic.

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Section: Efficacy Of Aunr@rf/pptt In Cellular Growth Inhibition In VImentioning

confidence: 99%

Efficacy, long-term toxicity, and mechanistic studies of gold nanorods photothermal therapy of cancer in xenograft mice

Ali

Rahman

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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198

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“…Thus, we hypothesized that the use of AuNRs allows us to apply near-infrared (NIR) laser to generate heat efficiently through nonradiative processes (13,30,31). AuNRs, due to their unique chemical, physical, and optical properties, have been used in drug delivery (32), bioimaging, and PPTT of cancer (33)(34)(35)(36). NIR light is a low energetic (safe) light that can deeply penetrate the tissues, which could potentially enhance the AuNRs' effects on cytoskeletal proteins and inhibit migration.…”

Section: Significancementioning

confidence: 99%

Targeting cancer cell integrins using gold nanorods in photothermal therapy inhibits migration through affecting cytoskeletal proteins

Ali

Tang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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159

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Metastasis is responsible for most cancer-related deaths, but the current clinical treatments are not effective. Recently, gold nanoparticles (AuNPs) were discovered to inhibit cancer cell migration and prevent metastasis. Rationally designed AuNPs could greatly benefit their antimigration property, but the molecular mechanisms need to be explored. Cytoskeletons are cell structural proteins that closely relate to migration, and surface receptor integrins play critical roles in controlling the organization of cytoskeletons. Herein, we developed a strategy to inhibit cancer cell migration by targeting integrins, using Arg-Gly-Asp (RGD) peptide-functionalized gold nanorods. To enhance the effect, AuNRs were further activated with 808-nm near-infrared (NIR) light to generate heat for photothermal therapy (PPTT), where the temperature was adjusted not to affect the cell viability/proliferation. Our results demonstrate changes in cell morphology, observed as cytoskeleton protrusions-i.e., lamellipodia and filopodia-were reduced after treatment. The Western blot analysis indicates the downstream effectors of integrin were attracted toward the antimigration direction. Proteomics results indicated broad perturbations in four signaling pathways, Rho GTPases, actin, microtubule, and kinases-related pathways, which are the downstream regulators of integrins. Due to the dominant role of integrins in controlling cytoskeleton, focal adhesion, actomyosin contraction, and actin and microtubule assembly have been disrupted by targeting integrins. PPTT further enhanced the remodeling of cytoskeletal proteins and decreased migration. In summary, the ability of targeting AuNRs to cancer cell integrins and the introduction of PPTT stimulated broad regulation on the cytoskeleton, which provides the evidence for a potential medical application for controlling cancer metastasis.gold nanorods | cytoskeleton | integrin | metastasis | plasmonic photothermal therapy

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“…Superficial tissues had numerous small vessels, while larger blood vessels were visible in the deep tissues In the present study, there were two challenges; the first was to achieve bactericidal effect of PPTT against ESβL Klebsiella pneumoniae and the second was enhancement of fistula healing without evidence of hyperthermia side effects on the tissues. Regarding first one, plasmonic photothermal therapy has been extensively investigated (in vitro) as an alternative technique in the biomedical area like determination of its bactericidal and antibiofilm activities against different strains of oral microorganisms (Castillo-Martínez, et al, 2015) [30], using of covalently primary antibodies linked gold nanorods to selectively destroy the pathogenic Gram-negative bacterium, Pseudomonas aeruginosa after exposure to near-infrared radiation (norman, et al, 2008) [31], using surface plasmonic resonance-induced photo-activation of gold nanoparticles as bactericidal agents against methicillin-resistant Staphylococcus aureus (Mocan, et al, 2014) [32], developing a drug delivery platform where gold nanorods (AunRs) are conjugated to rifampicin (RF), which is released after the uptake into macrophage cells (RAW264.7) [22] and studying the action of bactericidal gold nanoparticles on Escherichia coli (Cui, et al, 2012) [33]. In addition to that, a new antibacterial gold nanorod (GnR) conjugated magnetic nanoparticle (MnP) composite (GnR-MnP) was synthesized successfully for the eradication of antibiotic resistant nosocomial pathogens in water to improve the water quality (Ramasamy, et al, 2014) [34].…”

Section: Histopathoilogical Evaluationmentioning

confidence: 99%

“…Therefore, it is necessary to discover new antimicrobial compounds against ESβL-producing K. pneumoniae strains. Abundant improvements in nanotechnology have delivered a hard basis for using nanoparticles (nPs) in the battle against pathogenic microorganisms, containing multidrug resistant bacteria (Hernandez-Delgadillo, et al; 2013, badireddy, et al; 2014 and Ali et al; 2016) [20,21,22]. numerous works have studied the effectiveness of PDT for disinfection of oral pathogens; but the usage of PPTT against oral pathogens has not been sufficient discovered (badireddy, et al; 2014) [21].…”

Section: Introductionmentioning

confidence: 99%

Novel Clinical Trial for Treatment of Infected Subcutaneous Fistula in Female Griffon Dog using Gold Nano-Rod Assisted Near-Infrared Plasmonic Photothermal Therapy

Farghali¹,

Ali²,

Ali³

et al. 2017

IJBB

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Abstract:Raises in the occurrence of antibiotic resistant bacterial infections need novel methods for control. It is currently clear that a nanotechnology-driven method using nanoparticles to target and terminate pathogenic bacteria can be positively applied. Plasmonic photothermal therapy (PPTT) is a hopeful minimally-invasive antibacterial therapy as well as oncological treatment strategy where plasmonic nanoparticles are used to transform near infrared light to localized heat to cause cell death, mainly through apoptosis and/ or necrosis. The objective of this work was to detect the clinical bactericidal activities of gold nanorods (AunRs) using plasmonic photothermal therapy (PPTT) against pathogenic extended spectrum Beta Lactamase (ESβL) Klebsiella pneumoniae as well as apoptotic actions against pyogenic membrane of chronic subcutaneous fistula had no tendency to heal in clinically affected eight years old Griffon female dog. The fistula was infiltrated along its pyogenic wall and intraluminal in multiple spots with AuNR at 7.5 nM concentration and then exposed to an 808 nm diode laser with power of 5.8 W/cm2 and spot size about 5.6 mm2. The PPTT session was repeated every two weeks for four successive sessions. The evaluations of the curative response were done through clinical, bacteriological and histopathoilogical repetitive examinations. Clinically, the purulent discharge decreased in the quantity until it disappeared at the third PPTT session and complete regression of the fistula occurred after the fourth PPTT application. Bacteriologically, Klebsiella pneumoniae isolate showed dramatic reduction in colony forming unit (CFU) count after first session and was completely absent at the fourth PPTT session. Regarding histopathology of the tissue specimens from infected fistula when the case was admitted to the clinic, there was massive liquefied necrotic area infiltrated mainly by neutrophils represented as grade +3 and after first session of PPTT, there was circumscribe necrotic area infiltrated by few numbers of neutrophils and represented as grade +1. After third session of PPTT, complete absence of necrotic tissues was recorded and new fibrous connective tissue formation was observed. Altogether, these outcomes powerfully recommend that AunRs could be a motivating choice to control antibiotic resistant bacterial infections as well as pyogenic conditions which have no tendency to heal 151

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Gold Nanorods as Drug Delivery Vehicles for Rifampicin Greatly Improve the Efficacy of Combating Mycobacterium tuberculosis with Good Biocompatibility with the Host Cells

Cited by 47 publications

References 50 publications

Efficacy, long-term toxicity, and mechanistic studies of gold nanorods photothermal therapy of cancer in xenograft mice

Efficacy, long-term toxicity, and mechanistic studies of gold nanorods photothermal therapy of cancer in xenograft mice

Targeting cancer cell integrins using gold nanorods in photothermal therapy inhibits migration through affecting cytoskeletal proteins

Novel Clinical Trial for Treatment of Infected Subcutaneous Fistula in Female Griffon Dog using Gold Nano-Rod Assisted Near-Infrared Plasmonic Photothermal Therapy

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