Gold Nanoparticles For Delivery Research Articles

Gold Nanoparticle Delivery of Glut1 SiRNA Facilitates Glucose Starvation Therapy in Lung Cancer.

Glucose transporter protein-1 (Glut1), is highly expressed in many cancer types and plays a crucial role in cancer progression through enhanced glucose transport. Its overexpression is associated with aggressive tumor behavior and poor prognosis. Herein, the nucleic acids modified gold nanoparticles (AuNPs) was synthesized to deliver small interfering RNA (siRNA) against Glut1 by microRNA 21 (miR-21) triggers toehold-mediated strand displacement reaction for lung cancer starvation therapy. Overexpression of miR-21 triggers toehold-mediated strand displacement, releasing the siRNA to knockdown of Glut1 in cancer cell instead of normal cell. Furthermore, the glucose oxidase-like activity of the AuNPs accelerates intracellular glucose consumption, promoting cancer cell starvation. The engineered AuNPs@anti-miR-21/siGlut1 complex inhibits cancer cell proliferation, xenograft tumor growth and promotes apoptosis through glucose starvation and ROS cascade signaling, underscoring its potential as an effective therapeutic strategy for lung cancer.

Focused Ultrasound as a Novel Non-Invasive Method for the Delivery of Gold Nanoparticles to Retinal Ganglion Cells.

The blood-retinal barrier (BRB) restricts the delivery of intravenous therapeutics to the retina, necessitating innovative approaches for treating retinal disorders. This study sought to explore the potential of focused ultrasound (FUS) to non-invasively deliver intravenously administered gold nanoparticles (AuNPs) across the BRB. FUS-BRB modulation can offer a novel method for targeted retinal therapy. AuNPs of different sizes and shapes were characterized, and FUS parameters were optimized to permeate the BRB without causing retinal damage in a rodent model. The delivery of 70-kDa dextran and AuNPs to the retinal ganglion cell (RGC) layer was visualized using confocal and two-photon microscopy, respectively. Histological and statistical analyses were conducted to assess the effectiveness and safety of the procedure. FUS-BRB modulation resulted in the delivery of dextran and AuNPs to the RGC and inner nuclear layer. Smaller AuNPs reached the retinal layers to a greater extent than larger ones. The delivery of dextran and AuNPs across the BRB with FUS was achieved without significant retinal damage. This investigation provides the first evidence, to our knowledge, of FUS-mediated AuNP delivery across the BRB, establishing a foundation for a targeted and non-invasive approach to retinal treatment. The results contribute to developing promising non-invasive therapeutic strategies in ophthalmology to treat retinal diseases. Modifying the BRB with ultrasound offers a targeted and non-invasive delivery strategy of intravenous therapeutics to the retina.

Facile fabrication of combination delivery of kaempferol and sorafenib with PEGylated gold nanoparticles delivery to breast cancer: Investigation of cytotoxicity and apoptosis induction

Current clinical therapies for invasive breast cancer have low therapeutic effectiveness and substantial systemic adverse effects, leading to poor patient compliance. In this investigation, we developed dual anticancer drugs (sorafenib (SFB) and kaempferol (KMF)) encapsulated in PEGylated gold nanomaterial (PEG-AuNPs@SFB/KMF) for a drug delivery system targeting breast cancer to circumvent this problem. Subsequent research examined whether pH affects drug release. The current study results show that sorafenib and kaempferol work better together than each treatment individually in eliciting cytotoxic effects. In vitro cytotoxicity studies confirmed that PEG-AuNPs@SFB/KMF were more effective than sorafenib alone in MCF-7 and MDA-MB-231 cells, with less toxicity in NIH3T3 cells. The cancer cell proliferation was measured by Click-iT EdU assay, which indicates that the NPs effectively induce apoptosis in cancer cells. The different biochemical staining (acridine orange and ethidium bromide (AO-EB and nuclear staining (DAPI)) methods confirmed the morphological investigation of the cells. PEG-AuNPs@SFB/KMF increased apoptosis ratio, confirmed by flow cytometric analysis via Annexin V-FITC/PI staining methods. Therefore, we believe that the built multifunctional nanocarrier based on developed nanoparticle delivery could be an alternative therapeutic strategy for breast cancer therapy.

Gold Nanoparticle Delivery to Solid Tumors by Macrophage Depletion, Hypoxia Inhibition, and Collagen Degradation

Gold Nanoparticle Delivery to Solid Tumors by Macrophage Depletion, Hypoxia Inhibition, and Collagen Degradation

Quantitative Comparison of Gold Nanoparticle Delivery via the Enhanced Permeation and Retention (EPR) Effect and Mesenchymal Stem Cell (MSC)-Based Targeting.

There are still some gaps in existing knowledge in the field of cancer nanotheranostics, e.g., the efficiency of nanoparticle-loaded cells for targeted delivery. In the current study, gold nanoparticles (Au NPs) were delivered to tumors in both subcutaneous tumor and lung metastasis tumor models by intravenous injection of either free Au NPs or of human bone marrow mesenchymal stem cells (MSCs), which were loaded with endocytosed Au NPs. By making injections with the same dose of administrated Au NPs, it was possible to directly compare tumor targeting of both delivery modes. Hereby, the passive targeting of tumor by the plain Au NPs was facilitated by the enhanced permeation and retention (EPR) effect. Au NP retention by tumors, as well as tumor penetration, were found to be improved up to 2.4-to-9.3-fold when comparing the MSC-mediated delivery of Au NPs to the delivery of the plain Au NPs via EPR effect on day 7 post administration. While the absolute retention of Au NPs in the tumor remained low, our data show that, upon injection of the same amount of Au NPs, in fact MSC-mediated delivery is quantitatively higher than EPR-mediated delivery of NPs by half an order of magnitude.

Treatment of Orthotopic U251 Human Glioblastoma Multiforme Tumors in NRG Mice by Convection-Enhanced Delivery of Gold Nanoparticles Labeled with the β-Particle-Emitting Radionuclide, 177Lu.

In this study, we investigated convection-enhanced delivery (CED) of 23 ± 3 nm gold nanoparticles (AuNPs) labeled with the β-particle-emitting radionuclide 177Lu (177Lu-AuNPs) for treatment of orthotopic U251-Luc human glioblastoma multiforme (GBM) tumors in NRG mice. The cytotoxicity in vitro of 177Lu-AuNPs (0.0-2.0 MBq, 4 × 1011 AuNPs) on U251-Luc cells was also studied by a clonogenic survival assay, and DNA double-strand breaks (DSBs) caused by β-particle emissions of 177Lu were measured by confocal immunofluorescence microscopy for γH2AX. NRG mice with U251-Luc tumors in the right cerebral hemisphere of the brain were treated by CED of 1.1 ± 0.2 MBq of 177Lu-AuNPs (4 × 1011 AuNPs). Control mice received unlabeled AuNPs or normal saline. Tumor retention of 177Lu-AuNPs was assessed by single-photon emission computed tomography/computed tomography (SPECT/CT) imaging and biodistribution studies. Radiation doses were estimated for the tumor, brain, and other organs. The effectiveness for treating GBM tumors was determined by bioluminescence imaging (BLI) and T2-weighted magnetic resonance imaging (MRI) and by Kaplan-Meier median survival. Normal tissue toxicity was assessed by monitoring body weight and hematology and blood biochemistry analyses at 14 d post-treatment. 177Lu-AuNPs (2.0 MBq, 4 × 1011 AuNPs) decreased the clonogenic survival of U251-Luc cells to 0.005 ± 0.002 and increased DNA DSBs by 14.3-fold compared to cells treated with unlabeled AuNPs or normal saline. A high proportion of 177Lu-AuNPs was retained in the U251-Luc tumor in NRG mice up to 21 d with minimal re-distribution to the brain or other organs. The radiation dose in the tumor was high (599 Gy). The dose in the normal right cerebral hemisphere of the brain excluding the tumor was 93-fold lower (6.4 Gy), and 2000-3000-fold lower doses were calculated for the contralateral left cerebral hemisphere (0.3 Gy) or cerebellum (0.2 Gy). The doses in peripheral organs were <0.1 Gy. BLI revealed almost complete tumor growth arrest in mice treated with 177Lu-AuNPs, while tumors grew rapidly in control mice. MRI at 28 d post-treatment and histological staining showed no visible tumor in mice treated with 177Lu-AuNPs but large GBM tumors in control mice. All control mice reached a humane endpoint requiring sacrifice within 39 d (normal saline) or 45 d post-treatment (unlabeled AuNPs), while 5/8 mice treated with 177Lu-AuNPs survived up to 150 d. No normal tissue toxicity was observed in mice treated with 177Lu-AuNPs. We conclude that CED of 177Lu-AuNPs was highly effective for treating U251-Luc human GBM tumors in the brain in NRG mice at amounts that were non-toxic to normal tissues. These 177Lu-AuNPs administered by CED hold promise for treating patients with GBM to prevent recurrence and improve long-term outcome.

Gold nanoparticle delivery to solid tumors: a multiparametric study on particle size and the tumor microenvironment.

Nanoparticle (NP) delivery to solid tumors remains an actively studied field, where several recent studies have shed new insights into the underlying mechanisms and the still overall poor efficacy. In the present study, Au NPs of different sizes were used as model systems to address this topic, where delivery of the systemically administered NPs to the tumor as a whole or to tumor cells specifically was examined in view of a broad range of tumor-associated parameters. Using non-invasive imaging combined with histology, immunohistochemistry, single-cell spatial RNA expression and image-based single cell cytometry revealed a size-dependent complex interaction of multiple parameters that promoted tumor and tumor-cell specific NP delivery. Interestingly, the data show that most NPs are sequestered by tumor-associated macrophages and cancer-associated fibroblasts, while only few NPs reach the actual tumor cells. While perfusion is important, leaky blood vessels were found not to promote NP delivery, but rather that delivery efficacy correlated with the maturity level of tumor-associated blood vessels. In line with recent studies, we found that the presence of specialized endothelial cells, expressing high levels of CD276 and Plvap promoted both tumor delivery and tumor cell-specific delivery of NPs. This study identifies several parameters that can be used to determine the suitability of NP delivery to the tumor region or to tumor cells specifically, and enables personalized approaches for maximal delivery of nanoformulations to the targeted tumor.

Peptide mediated targeted delivery of gold nanoparticles into the demyelination site ameliorates myelin impairment and gliosis

Drug development for multiple sclerosis (MS) clinical management focuses on both neuroprotection and repair strategies, and is challenging due to low permeability of the blood-brain barrier, off-target distribution, and the need for high doses of drugs. The changes in the extracellular matrix have been documented in MS patients. It has been shown that the expression of nidogen-1 increases in MS lesions. Laminin forms a stable complex with nidogen-1 through a heptapeptide which was selected to target the lesion area in this study. Here we showed that the peptide binding was specific to the injured area following lysophosphatidylcholine (LPC) induced demyelination. In vivo data showed enhanced delivery of the peptide-functionalized gold nanoparticles (Pep-GNPs) to the lesion area. In addition, Pep-GNPs administration significantly enhanced myelin content and reduced astrocyte/microglia activation. Results demonstrated the possibility of using this peptide to target and treat lesions in patients suffering from MS.

Biosynthesis, Characterization, Anticancer activity and Drug delivery of Gold Nanoparticles synthesised from local isolate of Proteus mirabilis

Intracellular metal nanoparticles are produced by a variety of bacteria. As aqueous gold reacts with the Proteus mirabilis, it grows resulting in the formation of gold nanoparticles. The use of microorganisms in nanoparticle synthesis is gaining traction as an environmentally sustainable and exciting gold recovery process. This study consist of biological synthesis of gold nanoparticles utilizing the culture supernatant of local bacteria. Proteus mirabilis isolates when treated with HAuCl₄ solution in 10⁻³ Mm, then AuNPs were characterized and examined for anticancer ability using MTT assay against MCF-7 breast cancer cell lines. The size of the gold nanoparticles was rather consistent 29.18-55.57nm. Anticancer behavior studies revealed that gold nanoparticles had an equivalent strong anticancer impact. On the MCF-7 cell line, the AuNP concentration of 400 g/ml showed the greatest decrease. In addition, the combination of 400 g/ml AuNPs + 20 μM cisplatin resulted in the greatest reduction in the MCF-7 cell line.

Impact of Tumor Barriers on Nanoparticle Delivery to Macrophages.

The delivery of therapeutic nanoparticles to target cells is critical to their effectiveness. Here we quantified the impact of biological barriers on the delivery of nanoparticles to macrophages in two different tissues. We compared the delivery of gold nanoparticles to macrophages in the liver versus those in the tumor. We found that nanoparticle delivery to macrophages in the tumor was 75% less than to macrophages in the liver due to structural barriers. The tumor-associated macrophages took up more nanoparticles than Kupffer cells in the absence of barriers. Our results highlight the impact of biological barriers on nanoparticle delivery to cellular targets.

Targeted delivery of gold nanoparticles by neural stem cells to glioblastoma for enhanced radiation therapy: a review.

Glioblastoma (GB) is the most malignant subtype of brain cancer derived from astrocytes in the brain. Radiotherapy is one of the standard treatments for GB patients, but its effectiveness is often limited by the radioresistance of aggressive GB cells. Higher dose of radiation needs to be applied to GB patients to eliminate these stubborn cells, but this also means more side effects on the adjacent healthy cells because the radiation beam could indistinguishably harm all cells exposed to it. In order to address this problem, various strategies have been studied to enhance the radiosensitivity among the radioresistant cell populations for targeted eradication of GB without harming other surrounding healthy cells. One of the promising strategies for radiosensitization is to use gold nanoparticles (AuNPs) which can enhance photoelectric effects within the radioresistant cells for higher killing efficiency even at low doses of radiation. Nonetheless, there is no evidence showing the capability of these nanoparticles to travel to brain tumor cells, therefore, the application of this nanotechnology is very much dependent on the development of a suitable carrier to deliver the AuNPs to the GB tumor sites specifically. In this review article, we discussed the potentials of neural stem cells (NSCs) as biological carriers to carry AuNPs to targeted GB tumor sites and provided new insights into the potential of NSC-based targeted delivery system for GB treatment. The information reported here may pave a new direction for clinical transformation of next-generation nanoparticle-assisted radiotherapy to optimize the efficacy of radiotherapy for GB treatment.

Pathways for Oral and Rectal Delivery of Gold Nanoparticles (1.7 nm) and Gold Nanoclusters into the Colon: Enteric-Coated Capsules and Suppositories.

Two ways to deliver ultrasmall gold nanoparticles and gold-bovine serum albumin (BSA) nanoclusters to the colon were developed. First, oral administration is possible by incorporation into gelatin capsules that were coated with an enteric polymer. These permit the transfer across the stomach whose acidic environment damages many drugs. The enteric coating dissolves due to the neutral pH of the colon and releases the capsule’s cargo. Second, rectal administration is possible by incorporation into hard-fat suppositories that melt in the colon and then release the nanocarriers. The feasibility of the two concepts was demonstrated by in-vitro release studies and cell culture studies that showed the easy redispersibility after dissolution of the respective transport system. This clears a pathway for therapeutic applications of drug-loaded nanoparticles to address colon diseases, such as chronic inflammation and cancer.

Ultrasound Microbubble-Facilitated Inner Ear Delivery of Gold Nanoparticles Involves Transient Disruption of the Tight Junction Barrier in the Round Window Membrane.

The application of ultrasound microbubbles (USMBs) enhances the permeability of the round window membrane (RWM) and improves drug delivery to the inner ear. In this study, we investigated the efficiency of USMB-aided delivery of chitosan-coated gold nanoparticles (CS-AuNPs) and the mechanism of USMB-mediated enhancement of RMW permeability. We exposed mouse inner ears to USMBs at an intensity of 2 W/cm2 and then filled the tympanic bulla with CS-AuNPs or fluorescein isothiocyanate-decorated CS-AuNPs (FITC-CS-AuNPs). The membrane uptake of FITC-CS-AuNPs and their depth of permeation into the three-layer structure of the RWM, with or without prior USMB treatment, were visualized by z-stack confocal laser scanning microscopy. Ultrastructural changes in the RWM due to USMB-mediated cavitation appeared as sunburn-like peeling and various degrees of depression in the RWM surface, with pore-like openings forming in the outer epithelium. This disruption of the outer epithelium was paralleled by a transient reduction in tight junction (TJ)-associated protein levels in the RWM and an enhanced delivery of FITC-CS-AuNPs into the RWM. Without prior USMB exposure, the treatment with CS-AuNPs also caused a noticeable reduction in TJ proteins of the RWM. Our findings indicated that the combined treatment with USMBs and CS-AuNPs represents a promising and efficient drug and gene delivery vehicle for a trans-RWM approach for inner ear therapy. The outer epithelial layer of the RWM plays a decisive role in controlling the transmembrane transport of substances such as CS-AuNPs following the administration of USMBs. Most importantly, the enhanced permeation of AuNPs involved the transient disruption of the TJ-created paracellular barrier in the outer epithelium of the RWM.

Theoretical evaluation of enhanced gold nanoparticle delivery to PC3 tumors due to increased hydraulic conductivity or recovered lymphatic function after mild whole body hyperthermia.

The objective of this study is to investigate the effect of hyperthermia-induced improvement of hydraulic conductivity and lymphatic function on both tumoral IFP reduction and nanoparticle delivery to PC3 tumors. We developed a theoretical model for nanoparticle transport in a tumor incorporating Starling's law, Darcy's law, transient convection, and diffusion of chemical species in porous media, and nanoparticle accumulation in tumors. Results have shown that both mechanisms were effective to decrease the IFP at the tumor center from 1600 Pa in the control without heating to 800 Pa in tumors with whole body heating. IFP reductions not only elevate the nanoparticle concentration in the tumor, but also result in a more uniform nanoparticle concentration in the tumor than that in the control without heating. Due to the IFP reductions at the tumor center and/or local blood perfusion increases, the final amount of accumulated nanoparticles in the tumor increased by more than 35-95% when compared to the control without heating. We conclude that increases in the hydraulic conductivity and recovery of lymphatic functions are possible mechanisms that lead to IFP reductions and enhancement in nanoparticle deposition in PC3 tumors observed in our in vivo experimental studies.

Exploiting the efficacy of Tyro3 and folate receptors to enhance the delivery of gold nanoparticles into colorectal cancer cells in vitro.

Colorectal cancer (CRC) is the fourth most common cancer in the world. Due to its asymptomatic nature, CRC is diagnosed at an advanced stage where the survival rate is <5%. Besides, CRC treatment using chemotherapy, radiotherapy and surgery often causes undesirable side-effects. As such, gold nanoparticles (GNPs) are envisaged in the field for the diagnosis and treatment of CRC. GNPs have unique physical, chemical and electrical properties at the nanoscale which make them suitable for application in biomedicine. However, for GNPs to become clinically effective, their internalisation efficiency in cancer cells must be enhanced. Folate receptor-α (FR) is overexpressed in CRC cells wherein FR helps in the uptake of folic acid within the cells. Tyro3, a novel tyrosine kinase receptor, drives cell proliferation and its overexpression is correlated with poor prognosis in CRC. Their upregulated expression in CRC cells relative to normal cells makes them an ideal target for GNPs using active targeting. Therefore, in this study receptors FR and Tyro3 were simultaneously targeted using specific antibody-coated GNPs in order to enhance the uptake and internalisation of GNPs in CRC cells in vitro. Four different types of coated-GNPs were synthesised GNPs-PEG, GNPs-anti-FR, GNPs-anti-Tyro3 and GNPs-anti-(FR + Tyro3) and incubated (0–50 ng) with three CRC cell lines namely CRL1790, CRL2159 and HCT116. Simultaneous targeting of these receptors by GNPs-anti-(FR + Tyro3) was found to be the most effective in internalisation in CRC cells compared with GNPs targeted singly to FR or Tyro3 (p <0.05). Besides this, results show that Tyro3 mediated similar internalisation efficacy to FR (p <0.05) in CRC cells using ICP-OES.

Assessing the Role of Modern Excipients for Delivery of Gold Nanoparticles

Using the drug delivery approach, we explain the role lipids and polymers perform in the delivery of gold nanoparticles. They were tested alongside drug and polymer compatibility using pharmacodynamics and pharmacokinetics. The collected data demonstrate the production of gold nanoparticles' stability and strong therapeutic effects. We illustrate some of the intriguing categories of targeting systems for the delivery of Au G Nanoparticles that are under development. Polymers containing reactive functional groups to combine targeting binding sites, cell receptors, or drugs are also coated with nanoparticles engineered for biomedical applications. The present review focuses on utilization of modern excipients, lipids, polymers in formulation of delivery systems that can efficiently delivery the gold nanoparticles. Gold nanoparticles have outranged in their use for treating wide health diseases with limited side effects. The next generation medical deliverables are majorly focused on gold nanoparticles.&#x0D; Keywords: Gold nanoparticles, Lipids, Polymers, Delivery systems, Excipients, Diseases.

Portfolio Targeting Strategy To Realize the Assembly and Membrane Fusion-Mediated Delivery of Gold Nanoparticles to Mitochondria for Enhanced NIR Photothermal Therapies.

Targeting mitochondria has always been a challenging goal for therapeutic nanoparticle agents due to their heterotypic features and size, which usually lead to a lysosome/endosome endocytosis pathway. To overcome this limitation, in this work, a portfolio targeting strategy combining a small targeting molecule with a biomembrane was developed. Modification of small targeting molecule H2N-TPP on gold nanoparticles (GNPs) could not only facilitate the mitochondrial targeting but could also induce gold nanoparticle assembly. Therefore, the GNPs were endowed with good absorption and photothermal conversion abilities in the near-infrared (NIR) region. Meanwhile, a biomimetic strategy was adopted by wrapping the gold nanoparticle assembly (GNA) with cancer cell membranes (CCMs), which helped the GNA enter the prostatic cancer cell via a homotypic membrane-fusion process to avoid being trapped in endosomes/lysosomes. Thereafter, the GNA remaining in the cytoplasm could reach mitochondria more efficiently via guidance from H2N-TPP molecules. This "biomembrane-small molecule" combination targeting process was evidenced by fluorescence microscopy, and the highly efficient photothermal ablation of prostatic tumors in vivo was demonstrated. This portfolio targeting strategy could be extended to various nanodrugs/agents to realize an accurate subcellular targeting efficiency for cancer treatments or cell detections.

Transdermal Delivery of Gold Nanoparticles by a Soybean Oil-Based Oleogel under Iontophoresis.

Developing a facile mechanism for transporting nanoparticles across the whole skin by overcoming the stratum corneum is a challenging task. Herein, a stimuli-responsive and noninvasive transport of gold nanoparticles (AuNPs) has been reported through the fabrication of AuNP-incorporated soybean oil-based oleogels (AuG) using stearic acid as a gelator. A series of AuG was formulated by incorporating different proportions of AuNPs and a fixed amount of ciprofloxacin hydrochloride (drug) to establish that the composition with the highest concentration of AuNP (d-AuG4) was associated with the best iontophoretic response, validated via the corresponding in vitro drug release under AC field-induced iontophoresis. The sample d-AuG4 exhibited both drug and AuNP permeation across the whole pig ear skin thickness within as early as 1 h under the iontophoresis condition. With relevant control experiments, it was shown that the transport of AuNPs through the stratum corneum tissue and across the whole skin was possible upon the simultaneous fulfillment of two conditions: the presence of a skin permeation enhancer (stearic acid) within the oleogel and iontophoresis. While the literature reported that the permeation time for any free inorganic nanoparticle through the full-skin thickness varied within a few days, the permeation enhancement technique developed here reduced the corresponding delivery time for the AuNPs to a few hours. The extent of AuNP permeation that occurred in the microgram (per cm-2) scale was found to be affected by the duration of iontophoresis, suggesting that AuNPs' rapid transdermal entry can be simultaneously triggered and modulated by iontophoretic conditions.

ImmunoPET Imaging of Pancreatic Tumors with 89Zr-Labeled Gold Nanoparticle-Antibody Conjugates.

Targeted delivery in vivo remains an immense roadblock for the translation of nanomaterials into the clinic. The greatest obstacle is the mononuclear phagocyte system (MPS), which sequesters foreign substances from general circulation and causes accumulation in organs such as the liver and spleen. The purpose of this study was to determine whether attaching an active targeting antibody, 5B1, to the surface of gold nanoparticles and using clodronate liposomes to deplete liver and splenic macrophages could help to minimize uptake by MPS organs, increase targeted delivery to CA19.9-positive pancreatic tumors, and enhance pancreatic tumor delineation. To produce the antibody-gold nanoparticle conjugate (Ab-AuNP), the Ab was conjugated to p-isothiocyanatobenzyl-desferrioxamine (p-SCN-DFO) and subsequently conjugated to NHS-activated gold nanoparticles. The Ab-AuNP was characterized by transmission electron microscopy (TEM) and atomic force microscopy (AFM). Modified Lindmo assay was performed to assess binding affinity and internalization potential in vitro. The Ab-AuNP was radiolabeled with 89Zr and injected into CA19.9-positive BxPc-3 pancreatic orthotopic tumor-bearing mice pretreated with or without clodronate liposomes for PET imaging and biodistribution studies. Inductively coupled plasma-optical emission spectrometry (ICP-OES) analysis was used to confirm delivery of gold nanoparticles to BxPc-3 pancreatic subcutaneous xenografts. Mice pretreated with clodronate liposomes in an orthotopic setting demonstrated decreased liver uptake at early time points (12.2 ± 2.3% ID/g vs. 22.8 ± 3.8% ID/g at 24h) and increased tumor uptake at 120h (13.8 ± 8.0% ID/g vs. 6.0 ± 1.2% ID/g). This allowed for delineation of orthotopic pancreatic xenografts in significantly more mice treated with clodronate (6/6) than in mice not treated with clodronate (2/6) or mice injected with gold nanoparticles labeled with a nonspecific antibody (0/5). The combination of clodronate liposomes and an active targeting antibody on the surface of gold nanoparticles allowed for PET/CT imaging of subcutaneous and orthotopic pancreatic xenografts in mice.

Enhanced intracellular translocation and cytokine profiling of gold nanoparticles conjugated with human papilloma virus based (HPV-R9)cell-penetrating peptide in cancer cells

Functionalized gold nanoparticles are emerging as a promising nano carrier for targeted delivery of therapeutic molecules. The present study describes synthesis, characterization and intracellular delivery of gold nanoparticles (AuNPs) functionalized with L1 protein of human papilloma virus peptide (HPV) derived cell-penetrating peptide (CPP) conjugated with R9. HPV-R9 cell penetrating peptide conjugated with AuNPs (fAuNPs) was characterized using UV-visible and Fourier Transform Infrared (FTIR) spectroscopy, transmission electron microscopy, dynamic light scattering and zeta potential. The cellular uptake of fAuNPs was studied in Vero cells using fluorescence microscopy and flow cytometry. The fAuNPs displayed reversible low intracellular aggregation, ~20% cytotoxicity but high efficiency and stability in Vero cells. The cytokines study by real-time PCR was performed in 4T1 cells of the IL-4, IL-12 and IFN-g, found to be upregulated in comparison to control. The functionalized gold nanoparticles cell penetrating peptide show good intracellular transport to the cellular destinations. Results of this study demonstrate that cell penetrating peptide can be used along with gold nanoparticles for therapeutics application, particularly cancer.