Biodistribution of Dendrimer Nanocomposites for Nano-Radiation Therapy of Cancer

2006 ◽  
Author(s):  
Lajos P. Balogh ◽  
Mohamed K. Khan
Keyword(s):  
Surface Charge ◽  
Targeted Delivery ◽  
Tissue Sample ◽  
Surface Characteristics ◽  
Hybrid Nanoparticles ◽  
Mice Model ◽  
Rigorous Testing ◽  
Biological Environment ◽  
Multifunctional Nanocomposites

Multifunctional nanocomposites have an enormous scientific and practical future in medicine, especially in biomedical imaging and targeted delivery. Multifunctional composite nanodevices (CND) possess chemical and physical properties of all components, while interactions with the environment of the nanoparticle are dominated by the contact surface of the host molecule. Thus, if the surface is dominated by the organic component of a nano-sized organic-inorganic composite particle, an inorganic particle property can be manipulated in a biologic environment as if it belonged to an organic macromolecule. Composition, charge, and size of are critical in determining nanoparticle trafficking and uptake by organs, and therefore this knowledge is crucial for the development of cancer imaging and therapies. Specific biokinetics and biodistribution then can be influenced by correctly selecting size, and modifying surface characteristics, such as covalently attaching various targeting moieties to the surface forming biohybrids, regulating the surface charge, etc. Dendrimer nanocomposites are recently developed nearly monodisperse hybrid nanoparticles composed of macromolecular hosts and very small, uniformly dispersed inorganic guest domains combining desirable properties of the components. The surface groups control the interaction of these nanodevices with the biological environment. As a result of various synthetic options, the interior and/or the exterior of the host can be cationic, anionic, or non-ionic, depending on their termini and interior functionalities and the pH, and may involve multiple targeting moieties. We have synthesized gold/dendrimer nanocomposites to carry payload radiation and/or diagnostic moiety to specific targets. We examined the biodistribution of the templates and the corresponding gold/dendrimer nanocomposites. We employed the same dendrimer template and systematically varied the size, the surface charge and the composition. Biodistribution of {Au} gold/dendrimer nanodevices of various size (5, 12 and 22 nm) and surface charge (positive, negative) was investigated in mice models (B16 melanoma and DU145 human prostate cancer). Isotope neutron activation analysis (INAA) was used to measure the presence of Au(0) in the tissue sample. All {Au} gold/dendrimer-nanocomposites were assayed for their quantitative short-term (1hr), intermediate (1 day) and long-term (4 days) biodistribution throughout organs for clinical toxicity. Delivery of radiation dose was achieved by radioactive {198Au} composites in a mice model. We have shown that modulating surface charge and composition will greatly change the biodistribution characteristics of the nanodevices. Rigorous testing of the principles that govern nanoparticle interactions with the complex environment of biological systems will be critical for an understanding of how these nanodevices will behave in vivo.

Articulating Biomaterials

2015 ◽  
pp. 218-267 ◽  
Author(s):  
Vamsi Krishna Balla ◽  
Mitun Das ◽  
Someswar Datta ◽  
Biswanath Kundu
Keyword(s):  
Surface Modification ◽  
Clinical Performance ◽  
Decisive Role ◽  
Surface Characteristics ◽  
Surface Modification Techniques ◽  
Biological Environment ◽  
Surface Modified ◽  
In Vivo Effects

This chapter examines the importance of surface characteristics such as microstructure, composition, crystallographic texture, and surface free energy in achieving desired biocompatibility and tribological properties thereby improving in vivo life of artificial articulating implants. Current implants often fail prematurely due to inadequate mechanical, tribological, biocompatibility, and osseointegration properties, apart from issues related to design and surgical procedures. For long-term in vivo stability, artificial implants intended for articulating joint replacement must exhibit long-term stable articulation surface without stimulating undesirable in vivo effects. Since the implant's surface plays a vital and decisive role in their response to biological environment, and vice versa, surface modification of implants assumes a significant importance. Therefore, overview on important surface modification techniques, their capabilities, properties of modified surfaces/implants are presented in the chapter. The clinical performance of surface modified implants and new surfaces for potential next-generation articulating implant applications are discussed at the end.

scholarly journals In Vivo Fluorescence Imaging of Passive Inflammation Site Accumulation of Liposomes via Intravenous Administration Focused on Their Surface Charge and PEG Modification

Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 104
Author(s):  
Hisako Ibaraki ◽  
Akihiro Takeda ◽  
Naoki Arima ◽  
Naruhiro Hatakeyama ◽  
Yuuki Takashima ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Surface Charge ◽  
Intravenous Administration ◽  
Fluorescence Intensity ◽  
Cationic Liposome ◽  
Surface Characteristics ◽  
Cationic Liposomes ◽  
Anionic Liposomes ◽  
Peg Liposomes

Nanocarriers such as liposomes have been attracting attention as novel therapeutic methods for inflammatory autoimmune diseases such as rheumatoid arthritis and ulcerative colitis. The physicochemical properties of intravenously administered nanomedicines enable them to target inflamed tissues passively. However, few studies have attempted to determine the influences of nanoparticle surface characteristics on inflammation site accumulation. Here, we aimed to study the effects of polyethylene glycol (PEG) modification and surface charge on liposome ability to accumulate in inflammatory sites and be uptake by macrophages. Four different liposome samples with different PEG modification and surface charge were prepared. Liposome accumulation in the inflammation sites of arthritis and ulcerative colitis model mice was evaluated by using in vivo imaging. There was greater PEG-modified than unmodified liposome accumulation at all inflammation sites. There was greater anionic than cationic liposome accumulation at all inflammation sites. The order in which inflammation site accumulation was confirmed was PEG-anionic > PEG-cationic > anionic > cationic. PEG-anionic liposomes had ~2.5× higher fluorescence intensity than PEG-cationic liposomes, and the PEG-liposomes had ~2× higher fluorescence intensity than non-PEG liposomes. All liposomes have not accumulated at the inflammation sites in healthy mice. Furthermore, cationic liposomes were taken up to ~10× greater extent by RAW264.7 murine macrophages. Thus, PEG-cationic liposomes that have the ability to accumulate in inflammatory sites via intravenous administration and to be taken up by macrophages could be useful.

scholarly journals Hybrid Nanoparticles as an Efficient Porphyrin Delivery System for Cancer Cells to Enhance Photodynamic Therapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Letícia B. Silva ◽  
Kelly A. D. F. Castro ◽  
Caroline E. A. Botteon ◽  
Cristiano L. P. Oliveira ◽  
Roberto S. da Silva ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Photophysical Properties ◽  
Chemical Properties ◽  
Hybrid Nanostructures ◽  
Hybrid Nanoparticles ◽  
Invasive Approach ◽  
Oncological Diseases ◽  
Spherical Structures ◽  
Biological Environment

Photodynamic therapy (PDT) is a potential non-invasive approach for application in oncological diseases, based on the activation of a photosensitizer (PS) by light at a specific wavelength in the presence of molecular oxygen to produce reactive oxygen species (ROS) that trigger the death tumor cells. In this context, porphyrins are interesting PS because they are robust, have high chemical, photo, thermal, and oxidative stability, and can generate singlet oxygen (1O2). However, porphyrins exhibit low solubility and a strong tendency to aggregate in a biological environment which limits their clinical application. To overcome these challenges, we developed hybrid nanostructures to immobilize 5,10,15,20-tetrakis[(4-carboxyphenyl) thio-2,3,5,6-tetrafluorophenyl] (P), a new third-generation PS. The biological effect of this system was evaluated against bladder cancer (BC) cells with or without light exposition. The nanostructure composed of lipid carriers coated by porphyrin-chitosan (P-HNP), presented a size of ca. 130 nm and low polydispersity (ca. 0.25). The presence of the porphyrin-chitosan (P-chitosan) on lipid nanoparticle surfaces increased the nanoparticle size, changed the zeta potential to positive, decreased the recrystallization index, and increased the thermal stability of nanoparticles. Furthermore, P-chitosan incorporation on nanoparticles increased the stability and enhanced the self-organization of the system and the formation of spherical structures, as observed by small-angle X-ray scattering (SAXS) analysis. Furthermore, the immobilization process maintained the P photoactivity and improved the photophysical properties of PS, minimizing its aggregation in the cell culture medium. In the photoinduction assays, the P-HNP displayed high phototoxicity with IC50 3.2-folds lower than free porphyrin. This higher cytotoxic effect can be correlated to the high cellular uptake of porphyrin immobilized, as observed by confocal images. Moreover, the coated nanoparticles showed mucoadhesive properties interesting to its application in vivo. Therefore, the physical and chemical properties of nanoparticles may be relevant to improve the porphyrin photodynamic activity in BC cells.

Articulating Biomaterials

2018 ◽  
pp. 859-910
Author(s):  
Vamsi Krishna Balla ◽  
Mitun Das ◽  
Someswar Datta ◽  
Biswanath Kundu
Keyword(s):  
Surface Modification ◽  
Clinical Performance ◽  
Decisive Role ◽  
Surface Characteristics ◽  
Surface Modification Techniques ◽  
Biological Environment ◽  
Surface Modified ◽  
In Vivo Effects

This chapter examines the importance of surface characteristics such as microstructure, composition, crystallographic texture, and surface free energy in achieving desired biocompatibility and tribological properties thereby improving in vivo life of artificial articulating implants. Current implants often fail prematurely due to inadequate mechanical, tribological, biocompatibility, and osseointegration properties, apart from issues related to design and surgical procedures. For long-term in vivo stability, artificial implants intended for articulating joint replacement must exhibit long-term stable articulation surface without stimulating undesirable in vivo effects. Since the implant's surface plays a vital and decisive role in their response to biological environment, and vice versa, surface modification of implants assumes a significant importance. Therefore, overview on important surface modification techniques, their capabilities, properties of modified surfaces/implants are presented in the chapter. The clinical performance of surface modified implants and new surfaces for potential next-generation articulating implant applications are discussed at the end.

scholarly journals On-demand pH-sensitive surface charge-switchable polymeric micelles for targeting Pseudomonas aeruginosa biofilms development

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiangjun Chen ◽  
Rong Guo ◽  
Changrong Wang ◽  
Keke Li ◽  
Xinyu Jiang ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Surface Charge ◽  
Bacterial Resistance ◽  
Polymeric Micelles ◽  
Effective Means ◽  
Ph Sensitive ◽  
Bacterial Biofilm ◽  
Mice Model ◽  
On Demand

AbstractBacterial biofilm is the complicated clinical issues, which usually results in bacterial resistance and reduce the therapeutic efficacy of antibiotics. Although micelles have been drawn attention in treatment of the biofilms, the micelles effectively permeate and retain in biofilms still facing a big challenge. In this study, we fabricated on-demand pH-sensitive surface charge-switchable azithromycin (AZM)-encapsulated micelles (denoted as AZM-SCSMs), aiming to act as therapeutic agent for treating Pseudomonas aeruginosa (P. aeruginosa) biofilms. The AZM-SCSMs was composed of poly(l-lactide)-polyetherimide-hyd-methoxy polyethylene glycol (PLA-PEI-hyd-mPEG). It was noteworthy that the pH-sensitive acylhydrazone bond could be cleaved in acidic biofilm microenvironment, releasing the secondary AZM-loaded cationic micelles based on PLA-PEI (AZM-SCMs) without destroying the micellar integrity, which could tailor drug-bacterium interaction using micelles through electrostatic attraction. The results proved that positively charged AZM-SCMs could facilitate the enhanced penetration and retention inside biofilms, improved binding affinity with bacterial membrane, and added drug internalization, thus characterized as potential anti-biofilm agent. The excellent in vivo therapeutic performance of AZM-SCSMs was confirmed by the targeting delivery to the infected tissue and reduced bacterial burden in the abscess-bearing mice model. This study not only developed a novel method for construction non-depolymerized pH-sensitive SCSMs, but also provided an effective means for the treatment of biofilm-related infections.

Folate-containing reduction-sensitive lipid–polymer hybrid nanoparticles for targeted delivery of doxorubicin

2015 ◽  
Vol 3 (4) ◽  
pp. 655-664 ◽  
Author(s):  
Bo Wu ◽  
Ping Yu ◽  
Can Cui ◽  
Ming Wu ◽  
Yang Zhang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Outer Layer ◽  
Targeted Delivery ◽  
Hybrid Nanoparticles ◽  
Polymer Hybrid

Lipid–polymer hybrid nanoparticles (FLPNPs) containing a folate targeted ligand and a reduction-sensitive outer layer were developed to enhance drug delivery efficacy in vitro and in vivo.

Preparation and Evaluation of Upconversion Nanoparticles Based miRNA Delivery Carrier in Colon Cancer Mice Model

2019 ◽  
Vol 15 (11) ◽  
pp. 2240-2250 ◽  
Author(s):  
Hao Shi ◽  
Gao-Feng Liang ◽  
Yang Li ◽  
Jing-Hua Li ◽  
Ai-Hua Jing ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Targeted Delivery ◽  
Lattice Structure ◽  
Tumor Therapy ◽  
Upconversion Emission ◽  
Significant Inhibition ◽  
Upconversion Nanoparticles ◽  
Mice Model ◽  
Vector Targeting

Therapeutic efficacy of solid tumor is often severely hampered by poor penetration of therapeutics into diseased tissues and lack of tumor targeting. In this study, the functionalized upconversion nanoparticles (UCNP)-based delivery vector targeting cancer cells was developed. Firstly, NaYF4:Yb/Tm (UCNP) was prepared with the solvothermal method for the uniform nanoparticle size and brilliant lattice structure. The SiO2 coated UCNP was demonstrated a high upconversion emission and good monodispersity, which was coupled with polyetherimide (PEI) and miR-145 vector. Then, it was further functionalized via hyaluronic acid (HA) (UCNP/PEI/HA Nanocomplex, UCNPs) coating for the targeted delivery and improved biocompatibility. The UCNPs/miR-145 displays an excellent biocompatibility, a high level of cellular uptake and miR-145 expression, which results in a significant cell cycle arrest in G1, and induces CCND1, CDK6 and CCNE2 proteins downregulation. In vivo, the HA-coated UCNPs were enriched at the tumor site by targeting and retention effects, which resulted in a significant inhibition of tumor growth. Histological experiments demonstrated that UCNPs did not show significant toxicity in mice colon cancer model. Taken together, a UCNPs-based delivery platform was successfully constructed and used for miRNA target delivery, which provided a new method and idea for bioengineering and nanotechnology-based tumor therapy.

Potential in vitro and in vivo colon specific anticancer activity in a HCT-116 xenograft nude mice model: targeted delivery using enteric coated folate modified nanoparticles

RSC Advances ◽  
2015 ◽  
Vol 5 (21) ◽  
pp. 16507-16520 ◽  
Author(s):  
Renuka Khatik ◽  
Pankaj Dwivedi ◽  
Vijayabhaskar Reddy Junnuthula ◽  
Komal Sharma ◽  
Krishna Chuttani ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Colon Cancer ◽  
Targeted Delivery ◽  
Mice Model ◽  
Specific Targeting ◽  
Nude Mice Model ◽  
Hct 116 ◽  
Enteric Coated

ES–FA–CU–GdNP drug delivery system has been developed for specific targeting in colon cancer and has the promise to address overexpressed FRs.

Biomedical applications: Pitfalls in the practice

1994 ◽  
Vol 52 ◽  
pp. 378-379
Author(s):  
J. D. Shelburne ◽  
Peter Ingram ◽  
Victor L. Roggli ◽  
Ann LeFurgey
Keyword(s):  
Operating Room ◽  
Liquid Nitrogen ◽  
Lung Tissue ◽  
Biomedical Applications ◽  
Microprobe Analysis ◽  
Tissue Sample ◽  
Cellular Level ◽  
Tissue Samples ◽  
Asbestos Fibers

At present most medical microprobe analysis is conducted on insoluble particulates such as asbestos fibers in lung tissue. Cryotechniques are not necessary for this type of specimen. Insoluble particulates can be processed conventionally. Nevertheless, it is important to emphasize that conventional processing is unacceptable for specimens in which electrolyte distributions in tissues are sought. It is necessary to flash-freeze in order to preserve the integrity of electrolyte distributions at the subcellular and cellular level. Ideally, biopsies should be flash-frozen in the operating room rather than being frozen several minutes later in a histology laboratory. Electrolytes will move during such a long delay. While flammable cryogens such as propane obviously cannot be used in an operating room, liquid nitrogen-cooled slam-freezing devices or guns may be permitted, and are the best way to achieve an artifact-free, accurate tissue sample which truly reflects the in vivo state. Unfortunately, the importance of cryofixation is often not understood. Investigators bring tissue samples fixed in glutaraldehyde to a microprobe laboratory with a request for microprobe analysis for electrolytes.

Sign in / Sign up

Export Citation Format

Share Document