scholarly journals Differently PEGylated Polymer Nanoparticles for Pancreatic Cancer Delivery: Using a Novel Near-Infrared Emissive and Biodegradable Polymer as the Fluorescence Tracer

2021 ◽  
Vol 9 ◽  
Author(s):  
Huazhong Cai ◽  
Yanxia Chen ◽  
Liusheng Xu ◽  
Yingping Zou ◽  
Xiaoliang Zhou ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Near Infrared ◽  
Hydrophobic Interactions ◽  
Polymeric Nanoparticles ◽  
Fluorescent Nanoparticles ◽  
Pegylated Nanoparticles ◽  
Poly Ethylene ◽  
Tumor Accumulation

In this study, a chemically synthetic polymer, benzo[1,2-b:4,5-b′]difuran(BDF)-based donor–acceptor copolymer PBDFDTBO, was individually coated by amphiphilic poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-PCL) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(polyethylene glycol) (DSPE-PEG or PEG-DSPE), to form stably fluorescent nanoparticles in the near-infrared (NIR) window. The physicochemical properties of the synthesized nanoparticles were characterized and compared, including their size, surface charge, and morphology. In addition, in vitro studies were also performed using two pancreatic cancer cell lines, assessing the cell viability of the PBDFDTBO-included PEGylated nanoparticles formulations. Moreover, in vivo studies were also conducted, using subcutaneous murine cancer models to investigate the polymeric nanoparticles’ circulation time, tumor accumulation, and preferred organ biodistribution. The overall results demonstrated that even with the same PEGylated surface, the hydrophobic composition anchored on the encapsulated PBDFDTBO core strongly affected the biodistribution and tumor accumulation of the nanoparticles, to a degree possibly determined by the hydrophobic interactions between the hydrophobic segment of amphiphilic polymers (DSPE or PCL moiety) and the enwrapped PBDFDTBO. Both PEGylated nanoparticles were compared to obtain an optimized coating strategy for a desired biological feature in pancreatic cancer delivery.

scholarly journals Biocompatible and Biodegradable Magnesium Oxide Nanoparticles with In Vitro Photostable Near-Infrared Emission: Short-Term Fluorescent Markers

Nanomaterials ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 1360 ◽  
Author(s):  
Asma Khalid ◽  
Romina Norello ◽  
Amanda N. Abraham ◽  
Jean-Philippe Tetienne ◽  
Timothy J. Karle ◽  
...  
Keyword(s):  
Magnesium Oxide ◽  
In Vivo Imaging ◽  
Near Infrared ◽  
Cultured Cells ◽  
Infrared Emission ◽  
Fluorescent Nanoparticles ◽  
Short Term ◽  
Fluorescent Markers

Imaging of biological matter by using fluorescent nanoparticles (NPs) is becoming a widespread method for in vitro imaging. However, currently there is no fluorescent NP that satisfies all necessary criteria for short-term in vivo imaging: biocompatibility, biodegradability, photostability, suitable wavelengths of absorbance and fluorescence that differ from tissue auto-fluorescence, and near infrared (NIR) emission. In this paper, we report on the photoluminescent properties of magnesium oxide (MgO) NPs that meet all these criteria. The optical defects, attributed to vanadium and chromium ion substitutional defects, emitting in the NIR, are observed at room temperature in NPs of commercial and in-house ball-milled MgO nanoparticles, respectively. As such, the NPs have been successfully integrated into cultured cells and photostable bright in vitro emission from NPs was recorded and analyzed. We expect that numerous biotechnological and medical applications will emerge as this nanomaterial satisfies all criteria for short-term in vivo imaging.

A GPC1-targeted and gemcitabine-loaded biocompatible nanoplatform for pancreatic cancer multimodal imaging and therapy

Nanomedicine ◽  
2019 ◽  
Vol 14 (17) ◽  
pp. 2339-2353 ◽  
Author(s):  
Wenli Qiu ◽  
Huifeng Zhang ◽  
Xiao Chen ◽  
Lina Song ◽  
Wenjing Cui ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Detection ◽  
Multimodal Imaging ◽  
Near Infrared ◽  
Therapeutic Potential ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Blood Biochemical

Aim: Biomarker-targeted nanocarrier holds promise for early diagnosis and effective therapy of cancer. Materials & methods: This work successfully designs and evaluates GPC1-targeted, gemcitabine (GEM)-loaded multifunctional gold nanocarrier for near-infrared fluorescence (NIRF)/MRI and targeted chemotherapy against pancreatic cancer in vitro and in vivo. Results: Blood biochemical and histological analyses show that the in vivo toxicity of GPC1-GEM-nanoparticles (NPs) was negligible. Both in vitro and in vivo studies demonstrate that GPC1-GEM-NPs can be used as NIRF/MR contrast agent for pancreatic cancer detection. Treatment of xenografted mice with GPC1-GEM-NPs shows a higher tumor inhibitory effect compared with controls. Conclusion: This novel theranostic nanoplatform provides early diagnostic and effective therapeutic potential for pancreatic cancer.

scholarly journals Co-Encapsulation and Co-Delivery of Peptide Drugs via Polymeric Nanoparticles

Polymers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 288 ◽  
Author(s):  
Ma Rie Kim ◽  
Teng Feng ◽  
Qian Zhang ◽  
Ho Yin Edwin Chan ◽  
Ying Chau
Keyword(s):  
Encapsulation Efficiency ◽  
Polymeric Nanoparticles ◽  
Double Emulsion ◽  
Peptide Ligands ◽  
Peptide Drugs ◽  
Vitro Assay ◽  
Poly Ethylene ◽  
Intracellular Targets

Combination therapy is a promising form of treatment. In particular, co-treatment of P3 and QBP1 has been shown to enhance therapeutic effect in vivo in treating polyglutamine diseases. These peptide drugs, however, face challenges in clinical administration due to poor stability, inability to reach intracellular targets, and lack of method to co-deliver both drugs. Here we demonstrate two methods of co-encapsulating the peptide drugs via polymer poly(ethylene glycol)-block-polycaprolactone (PEG-b-PCL) based nanoparticles. Nanoparticles made by double emulsion were 100–200 nm in diameter, with drug encapsulation efficiency of around 30%. Nanoparticles made by nanoprecipitation with lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (POPG) were around 250–300 nm in diameter, with encapsulation efficiency of 85–100%. Particles made with both formulations showed cellular uptake when decorated with a mixture of peptide ligands that facilitate endocytosis. In vitro assay showed that nanoparticles could deliver bioactive peptides and encapsulation by double emulsion were found to be more effective in rescuing cells from polyglutamine-induced toxicity.

scholarly journals Homologous and Mitochondrial Targeting Synergistic Induction of Apoptosis and Ferroptosis Enhanced PDT Performance Against Osteosarcoma HOS

2021 ◽  
Author(s):  
Yang Wang ◽  
Liang Zhang ◽  
Guosheng Zhao ◽  
Yuan Zhang ◽  
Fangbiao Zhan ◽  
...  
Keyword(s):  
Cell Line ◽  
Molecular Mechanisms ◽  
Near Infrared ◽  
Inhibitory Effect ◽  
Plga Nanoparticles ◽  
Mitochondrial Targeting ◽  
Dual Targeting ◽  
Poly Ethylene

Abstract Background: There have been no prominent advancements in osteosarcoma (OS) treatment in the past 20 years. Although photodynamic therapy (PDT) is an emerging technique for cancer therapy, its lack of targeting in OS treatment severely limits its applications.Methods: In this study, we constructed a potential theranostic nanoplatform by using (poly (ethylene glycol) polylactic-co-Glycolic acid (PEG-PLGA) nanoparticles (NPs) wrapping IR780 into the core (PEG-PLGA-IR780 NPs), which was further camouflaged with human OS cell membranes from the HOS cell line (MH-PEG-PLGA-IR780 NPs) to show homologous and mitochondrial targeting capacities. In addition, the potential underlying anticancer mechanisms of MH-PEG-PLGA-IR780 NPs-mediated PDT was investigated.Results: We demonstrated that the MH-PEG-PLGA-IR780 NPs had excellent tumor/mitochondrial targeting with the help of homologous targeting to HOS cell line. Moreover, the excellent photoacoustic (PA)/fluorescence (FL) imaging ability of MH-PEG-PLGA-IR780 NPs laid a foundation for further applications. Under near-infrared (NIR) irradiation, we demonstrated that dual-targeting NPs-mediated PDT could significantly induce HOS cell apoptosis and ferroptosis, and further explored apoptosis was triggered by cytochrome c-activated mitochondrial apoptosis (endogenous apoptosis), and the specific molecular mechanisms of ferroptosis is the activation of NCOA4-mediated ferritinophagy and the passivation of GPX4 in vitro, synergistically leading to the excessive accumulation of ROS. In addition, MH-PEG-PLGA-IR780 NPs-induced PDT also showed an obvious inhibitory effect on tumor growth in vivo. Conclusion: These results suggest the dual-targeting-based theranostic nanoplatform provides an effective method to improve PDT performance in OS and paves a new and promising way for OS therapy.

scholarly journals In vitro and in vivo investigation of chitosan–polylysine polymeric nanoparticles for ovalbumin and CpG co-delivery

RSC Advances ◽  
2017 ◽  
Vol 7 (63) ◽  
pp. 39962-39969 ◽  
Author(s):  
Yunfei Han ◽  
Qian Duan ◽  
Yanhui Li ◽  
Jian Tian
Keyword(s):  
Ethylene Glycol ◽  
Delivery System ◽  
Polymeric Nanoparticles ◽  
Poly Ethylene Glycol ◽  
Glycol Chitosan ◽  
Vaccine Delivery System ◽  
Electrostatic Binding ◽  
Poly Ethylene

A simple and powerful vaccine delivery system was developed by electrostatic binding of chitosan-based polycation methoxy poly(ethylene glycol)–chitosan–poly(l-lysine) (mPEG–CS–PLL) with ovalbumin (OVA) and cytosine–phosphate–guanine (CpG).

scholarly journals Simulation of the In Vivo Fate of Polymeric Nanoparticles Traced by Environment-Responsive Near-Infrared Dye: A Physiologically Based Pharmacokinetic Modelling Approach

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1271
Author(s):  
Lei Li ◽  
Haisheng He ◽  
Sifang Jiang ◽  
Jianping Qi ◽  
Yi Lu ◽  
...  
Keyword(s):  
Near Infrared ◽  
Polymeric Nanoparticles ◽  
Lymphatic Transport ◽  
Cellular Mechanisms ◽  
Physiologically Based Pharmacokinetic ◽  
Enhanced Permeability And Retention ◽  
Physiologically Based ◽  
Poly Ethylene ◽  
Near Infrared Dye

The application of physiologically based pharmacokinetic models to nanoparticles is still very restricted and challenging, owing to the complicated in vivo transport mechanisms involving nanoparticles, including phagocytosis, enhanced permeability and retention effects, cellular recognition, and internalisation, enzymatic degradation, lymphatic transport, and changes in physical properties. In our study, five nanoparticle formulations were synthesised using polycaprolactone as a framework material and methoxy poly (ethylene glycol)-poly(ε-caprolactone) as a long-circulating decorating material, as well as types of environmentally responsive near-infrared aza-boron-dipyrromethene dyes. According to quantification data and direct visualisation involving specific organs, a phagocytosis physiologically based pharmacokinetic model was developed to describe the dynamics of nanoparticles within and between organs in mice, considering cellular mechanisms involving phagocytosis and enhanced permeability and retention effects. Our results offer a better understanding of the in vivo fate of polymeric nanoparticles.

scholarly journals Polydopamine-Based “Four-in-One” Versatile Nanoplatforms for Targeted Dual Chemo and Photothermal Synergistic Cancer Therapy

Pharmaceutics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 507 ◽  
Author(s):  
Liu ◽  
Gao ◽  
Zhou ◽  
Nie ◽  
Cheng ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Anticancer Drug ◽  
Near Infrared ◽  
Polymeric Nanoparticles ◽  
Carcinoma Cells ◽  
Promising Strategy ◽  
Human Breast Carcinoma Cells ◽  
Mcf 7

Abstract: The development of versatile nanoscale drug delivery systems that integrate with multiple therapeutic agents or methods and improve the efficacy of cancer therapy is urgently required. To satisfy this demand, polydopamine (PDA)-modified polymeric nanoplatforms were constructed for the dual loading of chemotherapeutic drugs. The hydrophobic anticancer drug docetaxel (DTX) was loaded into the polymeric nanoparticles (NPs) which were fabricated from the star-shaped copolymer CA-PLGA. Then DTX-loaded NPs were coated with PDA, followed by conjugation of polyelethyl glycol (PEG)-modified targeting ligand aptamer AS1411(Apt) and adsorption of the hydrophilic anticancer drug doxorubicin (DOX). This “four-in-one” nanoplatform, referred to as DTX/NPs@PDA/DOX-PEG-Apt, demonstrated high near-infrared photothermal conversion efficiency and exhibited pH and thermo-responsive drug release behavior. Furthermore, it was able to specifically target MCF-7 human breast carcinoma cells and provide synergistic chemo-photothermal therapy to further improve the anticancer effect both in vitro and in vivo, providing a novel promising strategy for cancer therapy.

scholarly journals Near-infrared dye loaded polymeric nanoparticles for cancer imaging and therapy and cellular response after laser-induced heating

2014 ◽  
Vol 5 ◽  
pp. 313-322 ◽  
Author(s):  
Tingjun Lei ◽  
Alicia Fernandez-Fernandez ◽  
Romila Manchanda ◽  
Yen-Chih Huang ◽  
Anthony J McGoron
Keyword(s):  
Cancer Therapy ◽  
Cellular Response ◽  
Near Infrared ◽  
Polymeric Nanoparticles ◽  
Thermal Dose ◽  
Short Term ◽  
Synthesis Of Nanoparticles

Background: In the past decade, researchers have focused on developing new biomaterials for cancer therapy that combine imaging and therapeutic agents. In our study, we use a new biocompatible and biodegradable polymer, termed poly(glycerol malate co-dodecanedioate) (PGMD), for the synthesis of nanoparticles (NPs) and loading of near-infrared (NIR) dyes. IR820 was chosen for the purpose of imaging and hyperthermia (HT). HT is currently used in clinical trials for cancer therapy in combination with radiotherapy and chemotherapy. One of the potential problems of HT is that it can up-regulate hypoxia-inducible factor-1 (HIF-1) expression and enhance vascular endothelial growth factor (VEGF) secretion. Results: We explored cellular response after rapid, short-term and low thermal dose laser-IR820-PGMD NPs (laser/NPs) induced-heating, and compared it to slow, long-term and high thermal dose heating by a cell incubator. The expression levels of the reactive oxygen species (ROS), HIF-1 and VEGF following the two different modes of heating. The cytotoxicity of NPs after laser/NP HT resulted in higher cell killing compared to incubator HT. The ROS level was highly elevated under incubator HT, but remained at the baseline level under the laser/NP HT. Our results show that elevated ROS expression inside the cells could result in the promotion of HIF-1 expression after incubator induced-HT. The VEGF secretion was also significantly enhanced compared to laser/NP HT, possibly due to the promotion of HIF-1. In vitro cell imaging and in vivo healthy mice imaging showed that IR820-PGMD NPs can be used for optical imaging. Conclusion: IR820-PGMD NPs were developed and used for both imaging and therapy purposes. Rapid and short-term laser/NP HT, with a low thermal dose, does not up-regulate HIF-1 and VEGF expression, whereas slow and long term incubator HT, with a high thermal dose, enhances the expression of both transcription factors.

Bioinformatic inspired nanoparticles engineered for enhanced delivery to the bone.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14637-e14637
Author(s):  
Andrew Gdowski ◽  
Amalendu Ranjan ◽  
Jana Lampe ◽  
Victor Lin ◽  
Yu-Chieh Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Near Infrared ◽  
Infrared Imaging ◽  
Polymeric Nanoparticles ◽  
Extrusion Process ◽  
In Vitro Testing ◽  
Physico Chemical

e14637 Background: We have engineered a programmable-bioinspired nanoparticle (P-BiNP) delivery system to simultaneously target the bone and increase uptake in homotypic tumor cells by coating polymeric nanoparticles with programmed cancer cell membranes. This approach is unique in that we have incorporated relevant clinical bioinformatics data to guide the design of these nanoparticles. Methods: A gene ontology search identified potential homotypic cell-cell adhesion genes. These were cross referenced with RNAseq expression levels from patients with metastatic prostate cancer to various organ locations using the Cbioportal database. C4-2B prostate cancer cells were grown and stimulated to express membrane ɑVβ3 by treatment with recombinant human CXCL12. The cell membrane from these cancer cells were used to coat polymeric nanoparticles by an extrusion process. Physico-chemical optimization and characterization of the P-BiNPs was performed. In vitro testing was done with flow cytometry and MTT assays. A murine model was used with high resolution near infrared imaging to identify nanoparticle localization. Results: Analysis of RNAseq from mCRPC samples (n = 118) identified ITGB3 as increased in bone metastatic lesions compared to metastases from other sites (P < 0.0001). ITGB3 is a subunit of integrin ɑVβ3 and was selected as a target for enhancement to improve P-BiNP homotypic targeting and bone localization. After optimization, P-BiNPs showed optimal physico-chemical characteristics for drug delivery. Both in vitro testing and in vivo testing showed the P-BiNPs to be superior in homotypic uptake and localization to the bone. Conclusions: This platform of identifying clinically relevant targets for dual homotypic and bone targeting has potential as a strategy for treatment and imaging modalities in cancers that affects the bone as well as implications for delivering nanoparticles to other organs of interest.

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