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2.
Front Pharmacol ; 14: 1125093, 2023.
Article in English | MEDLINE | ID: mdl-37033603

ABSTRACT

Cancer causes significant mortality and morbidity worldwide, but existing pharmacological treatments are greatly limited by the inherent heterogeneity of cancer as a disease, as well as the unsatisfactory efficacy and specificity of therapeutic drugs. Biopharmaceutical barriers such as low permeability and poor water solubility, along with the absence of active targeting capabilities, often result in suboptimal clinical results. The difficulty of successfully reaching and destroying tumor cells is also often compounded with undesirable impacts on healthy tissue, including off-target effects and high toxicity, which further impair the ability to effectively manage the disease and optimize patient outcomes. However, in the last few decades, the development of nanotherapeutics has allowed for the use of rational design in order to maximize therapeutic success. Advances in the fabrication of nano-sized delivery systems, coupled with a variety of surface engineering strategies to promote customization, have resulted in promising approaches for targeted, site-specific drug delivery with fewer unwanted effects and better therapeutic efficacy. These nano systems have been able to overcome some of the challenges of conventional drug delivery related to pharmacokinetics, biodistribution, and target specificity. In particular, lipid-based nanosystems have been extensively explored due to their high biocompatibility, versatility, and adaptability. Lipid-based approaches to cancer treatment are varied and diverse, including liposomal therapeutics, lipidic nanoemulsions, solid lipid nanoparticles, nanostructured lipidic carriers, lipid-polymer nanohybrids, and supramolecular nanolipidic structures. This review aims to provide an overview of the use of diverse formulations of lipid-engineered nanotherapeutics for cancer and current challenges in the field, as researchers attempt to successfully translate these approaches from bench to clinic.

3.
Artif Cells Nanomed Biotechnol ; 50(1): 343-351, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36519372

ABSTRACT

In this study, Cannabis sativa roots extract has been employed for the biosynthesis of silver nanoparticles (AgNPs). The appearance of reddish-brown colour followed by absorption peak of AgNPs at 408 nm through UV-vis spectrophotometry suggested biosynthesis of AgNPs. The size of the particles ranged from 90-113 nm, confirmed using DLS and TEM along with zeta potential of -25.3 mV. The FTIR provided information regarding the phytochemical capping. The study was further elaborated for determining AgNPs antibacterial, antioxidant, and cellular toxicity using MIC, DPPH, MTT, and haemolytic assays, respectively. The AgNPs were significantly effective against Staphylococcus aureus (Gram-positive), as compared to that of Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli (Gram-negative). AgNPs also exhibited remarkable antioxidant potential wherein 58.01 ± 0.09% free radical scavenging was observed at a concentration of 100 µg/ml. AgNPs revealed lower cytotoxicity where cell viability was observed to be 52.38 ± 0.6% at a very high concentration of 500 µg/ml in HEK 293 cells. Further, very low toxicity was seen in RBCs i.e. 6.47 ± 0.04% at a high concentration of 200 µg/ml. Thus, the current study beholds anticipation that Cannabis sativa ethanolic root extract-mediated AgNPs may play a vital role in therapeutic.


Subject(s)
Cannabis , Metal Nanoparticles , Humans , Silver/pharmacology , Silver/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Metal Nanoparticles/chemistry , Microbial Sensitivity Tests , HEK293 Cells , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Escherichia coli , Hemolysis , Plant Extracts/pharmacology , Plant Extracts/chemistry
4.
Curr Pharm Biotechnol ; 23(14): 1721-1738, 2022.
Article in English | MEDLINE | ID: mdl-35016594

ABSTRACT

Among conventional treatment methodologies, surgery, hyperthermia, radiation, and chemotherapy have become integral components of treatment for most cancers. Radiation therapy in the treatment of many malignancies is always the better choice over surgery and chemotherapy. Ionizing radiation produced as a consequence of using these radiations has always been a concern in these treatment methods. Synthetic radio-protectors with their inherent limitations are being used to date to reduce the mortality of these radiations; still, it compromises the clinical efficacy of these administrations. Hence, investigations for alternative methods, including natural resources such as plant and fruit extracts, are being explored to treat radiation-mediated ailments. The present review article endeavors to provide a comprehensive, updated, and chronological account of these promising plants and fruit extracts and their bioactive principles as radio-protectors. We present the merits and demerits of radiation therapy and cell stress generation of reactive oxygen species (ROS) associated with radiation need and availability of radio-protectors. Finally, we discuss green-based bioactive compounds that have radioprotective properties.


Subject(s)
Biological Products , Radiation-Protective Agents , Radiation-Protective Agents/pharmacology , Radiation-Protective Agents/therapeutic use , Reactive Oxygen Species , Biological Products/pharmacology , Biological Products/therapeutic use , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Radiation, Ionizing , Plants
5.
Adv Pharmacol ; 91: 293-335, 2021.
Article in English | MEDLINE | ID: mdl-34099112

ABSTRACT

Critical advances have recently been made in the field of immunotherapy, contributing to an improved understanding of how to harness and balance the power of immune responses in the treatment of diseases such as cancer, cardiovascular disease, infectious diseases, and autoimmune diseases. Combining nanomedicine with immunotherapy provides the opportunity for customization, rational design, and targeting to minimize side effects and maximize efficacy. This review highlights current developments in the design and utilization of nano-based immunotherapy systems, including how rationally-designed nanosystems can target and modify immune cells to modulate immune responses in a therapeutic manner. We discuss the following topics: targeted immuno-engineered nanoformulations, commercial formulations, clinical applicability, challenges associated with current approaches, and future directions.


Subject(s)
Nanostructures , Neoplasms , Humans , Immunologic Factors , Immunotherapy , Nanomedicine , Neoplasms/drug therapy
6.
Biotechnol Adv ; 48: 107711, 2021.
Article in English | MEDLINE | ID: mdl-33592279

ABSTRACT

Biopolymers are of prime importance among which gum polysaccharides hold an eminent standing owing to their high availability and non-toxic nature. Gum biopolymers offer a greener alternative to synthetic polymers and toxic chemicals in the synthesis of metal nanostructures. Metal nanostructures accessible via eco-friendly means endow astounding characteristics to gum-based biocomposites in the field of diagnosis and therapy towards cancer diseases. In this review, assorted approaches for the assembly of nanomaterials mediated by gum biopolymers are presented and their utility in cancer diagnosis and therapy, e.g., bioimaging, radiotherapy, and phototherapy, are deliberated to provide a groundwork for future stimulative research.


Subject(s)
Nanostructures , Neoplasms , Humans , Neoplasms/diagnosis , Neoplasms/drug therapy , Phototherapy , Polymers , Polysaccharides
7.
Sci Rep ; 11(1): 3824, 2021 02 15.
Article in English | MEDLINE | ID: mdl-33589661

ABSTRACT

The present study aims at developing PGMD (poly-glycerol-malic acid-dodecanedioic acid)/curcumin nanoparticles based formulation for anticancer activity against breast cancer cells. The nanoparticles were prepared using both the variants of PGMD polymer (PGMD 7:3 and PGMD 6:4) with curcumin (i.e. CUR NP 7:3 and CUR NP 6:4). The size of CUR NP 7:3 and CUR NP 6:4 were found to be ~ 110 and 218 nm with a polydispersity index of 0.174 and 0.36, respectively. Further, the zeta potential of the particles was - 18.9 and - 17.5 mV for CUR NP 7:3 and CUR NP 6:4, respectively. The entrapment efficiency of both the nanoparticles was in the range of 75-81%. In vitro anticancer activity and the scratch assay were conducted on breast cancer cell lines, MCF-7 and MDA-MB-231. The IC50 of the nanoformulations was observed to be 40.2 and 33.6 µM at 48 h for CUR NP 7:3 and CUR NP 6:4, respectively, in MCF-7 cell line; for MDA-MB-231 it was 43.4 and 30.5 µM. Acridine orange/EtBr and DAPI staining assays showed apoptotic features and nuclear anomalies in the treated cells. This was further confirmed by western blot analysis that showed overexpression of caspase 9 indicating curcumin role in apoptosis.


Subject(s)
Antineoplastic Agents/administration & dosage , Curcumin/administration & dosage , Drug Carriers , Glycerol , Malates , Nanoparticles , Polymers , Apoptosis/drug effects , Breast Neoplasms/diagnosis , Breast Neoplasms/drug therapy , Breast Neoplasms/mortality , Cell Line, Tumor , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Carriers/chemical synthesis , Drug Carriers/chemistry , Drug Compounding , Drug Liberation , Female , Glycerol/chemical synthesis , Humans , Kinetics , Malates/chemical synthesis , Nanoparticles/chemistry , Nanoparticles/ultrastructure , Particle Size , Polymers/chemical synthesis , Spectrum Analysis
8.
Curr Drug Metab ; 22(4): 251-262, 2021.
Article in English | MEDLINE | ID: mdl-33234099

ABSTRACT

Impressive research steps have been taken for the treatment of neurological disorders in the last few decades. Still, effective treatments of brain related disorders are very less due to problems associated with crossing the blood-brain barrier (BBB), non-specific therapies, and delay in functional recovery of the central nervous system (CNS) after treatment. Striving for novel treatment options for neurological disorders, nanotechnology- derived materials, and devices have gained ground due to inherent features of derivatization/encapsulation with drugs as per the neurological ailments and pharmacological targets. Facile developments/syntheses of the nanomaterials-drug conjugates have also been the driving force for researchers to get into this field. Moreover, the tunable size and hydro/lipophilicity of these nanomaterials are the added advantages that make these materials more acceptable for CNS disorders. These nano-neurotherapeutics (NNTs) systems provide the platform for diagnosis, theranostics, treatments, restoration of CNS disorders, and encourage the translation of NNTs from "bench to bedside". Still, these techniques are in the primary stages of medical development. This review describes the latest advancements and future scenarios of developmental and clinical aspects of polymeric NNTs.


Subject(s)
Blood-Brain Barrier/metabolism , Central Nervous System Agents/administration & dosage , Central Nervous System Diseases/drug therapy , Nanoparticle Drug Delivery System/pharmacology , Theranostic Nanomedicine/trends , Animals , Clinical Trials as Topic , Disease Models, Animal , Humans , Nanoparticle Drug Delivery System/chemistry , Permeability/drug effects , Theranostic Nanomedicine/methods , Treatment Outcome
9.
Biomolecules ; 10(12)2020 12 16.
Article in English | MEDLINE | ID: mdl-33339083

ABSTRACT

This study aims to determine the anticancer efficacy of diosgenin encapsulated poly-glycerol malate co-dodecanedioate (PGMD) nanoparticles. Diosgenin loaded PGMD nanoparticles (variants 7:3 and 6:4) were synthesized by the nanoprecipitation method. The synthesis of PGMD nanoparticles was systematically optimized employing the Box-Behnken design and taking into account the influence of various independent variables such as concentrations of each PGMD, diosgenin and PF-68 on the responses such as size and PDI of the particles. Mathematical modeling was done using the Quadratic second order modeling method and response surface analysis was undertaken to elucidate the factor-response relationship. The obtained size of PGMD 7:3 and PGMD 6:4 nanoparticles were 133.6 nm and 121.4 nm, respectively, as measured through dynamic light scattering (DLS). The entrapment efficiency was in the range of 77-83%. The in vitro drug release studies showed diffusion and dissolution controlled drug release pattern following Korsmeyer-Peppas kinetic model. Furthermore, in vitro morphological and cytotoxic studies were performed to evaluate the toxicity of synthesized drug loaded nanoparticles in model cell lines. The IC50 after 48 h was observed to be 27.14 µM, 15.15 µM and 13.91 µM for free diosgenin, PGMD 7:3 and PGMD 6:4 nanoparticles, respectively, when administered in A549 lung carcinoma cell lines.


Subject(s)
Diosgenin/pharmacology , Drug Delivery Systems/methods , Glycerol/chemistry , Malates/chemistry , Nanoparticles/chemistry , Polymers/chemistry , A549 Cells , Acridine Orange , Antineoplastic Agents/pharmacology , Apoptosis , Cell Survival/drug effects , Drug Carriers , Drug Liberation , Dynamic Light Scattering , Ethidium/chemistry , Humans , In Vitro Techniques , Inhibitory Concentration 50 , Kinetics , Light , Models, Theoretical , Particle Size , Scattering, Radiation
10.
Int J Nanomedicine ; 9: 4631-48, 2014.
Article in English | MEDLINE | ID: mdl-25336944

ABSTRACT

Near-infrared dyes can be used as theranostic agents in cancer management, based on their optical imaging and localized hyperthermia capabilities. However, their clinical translatability is limited by issues such as photobleaching, short circulation times, and nonspecific biodistribution. Nanoconjugate formulations of cyanine dyes, such as IR820, may be able to overcome some of these limitations. We covalently conjugated IR820 with 6 kDa polyethylene glycol (PEG)-diamine to create a nanoconjugate (IRPDcov) with potential for in vivo applications. The conjugation process resulted in nearly spherical, uniformly distributed nanoparticles of approximately 150 nm diameter and zeta potential -0.4±0.3 mV. The IRPDcov formulation retained the ability to fluoresce and to cause hyperthermia-mediated cell-growth inhibition, with enhanced internalization and significantly enhanced cytotoxic hyperthermia effects in cancer cells compared with free dye. Additionally, IRPDcov demonstrated a significantly longer (P<0.05) plasma half-life, elimination half-life, and area under the curve (AUC) value compared with IR820, indicating larger overall exposure to the theranostic agent in mice. The IRPDcov conjugate had different organ localization than did free IR820, with potential reduced accumulation in the kidneys and significantly lower (P<0.05) accumulation in the lungs. Some potential advantages of IR820-PEG-diamine nanoconjugates may include passive targeting of tumor tissue through the enhanced permeability and retention effect, prolonged circulation times resulting in increased windows for combined diagnosis and therapy, and further opportunities for functionalization, targeting, and customization. The conjugation of PEG-diamine with a near-infrared dye provides a multifunctional delivery vector whose localization can be monitored with noninvasive techniques and that may also serve for guided hyperthermia cancer treatments.


Subject(s)
Antineoplastic Agents/chemistry , Diamines/chemistry , Indocyanine Green/analogs & derivatives , Nanoconjugates/chemistry , Optical Imaging/methods , Polyethylene Glycols/chemistry , Algorithms , Animals , Antineoplastic Agents/pharmacokinetics , Cell Line, Tumor , Cell Proliferation/drug effects , Diamines/toxicity , Humans , Hyperthermia, Induced , Indocyanine Green/chemistry , Indocyanine Green/pharmacokinetics , Indocyanine Green/toxicity , Mice , Nanoconjugates/toxicity , Nanotechnology , Polyethylene Glycols/toxicity , Surgery, Computer-Assisted , Tissue Distribution
11.
RSC Adv ; 4(34): 17959-17968, 2014 Jan 01.
Article in English | MEDLINE | ID: mdl-24999382

ABSTRACT

In this study, we prepared novel poly(Glycerol malate co-dodecanedioate) (PGMD) NPs containing an imaging/hyperthermia agent (IR820) and a chemotherapeutic agent (doxorubicin, DOX). The PGMD polymer was prepared by thermal condensation. IR820 and DOX loaded PGMD NPs were prepared using the single oil emulsion technique. The size of the NPs measured was around 150 nm. Drug loading efficiency of DOX and IR820 was around 4% and 8%, respectively. An acidic environment (pH=5.0) induced higher DOX release as compared to pH=7.4. DOX release was also enhanced by exposure to laser, which increased the temperature to 42°C. Cytotoxicity of the drug loaded NPs was comparable in MES-SA but was higher in Dx5 cells compared to free drug (p<0.05). The combination of hyperthermia and chemotherapy improved cytotoxicity in both cell lines. The NP formulation significantly improved the plasma half-life of IR820 in mice after tail vein injection.

12.
J Photochem Photobiol B ; 136: 81-90, 2014 Jul 05.
Article in English | MEDLINE | ID: mdl-24859437

ABSTRACT

The purpose of this study was to prepare targeted Poly lactide-co-glycolide (PLGA) nanoparticles with simultaneous entrapment of indocyanine green (ICG) and doxorubicin (DOX) by surface decorating them with tumor specific monoclonal antibodies in order to achieve simultaneous therapy and imaging. ICG was chosen as an imaging and hyperthermia agent and DOX was used as a chemotherapeutic agent. ICG and DOX were incorporated into PLGA nanoparticles using the oil-in-water emulsion solvent evaporation technique. These nanoparticles were further surface decorated with antibodies against Human Epithelial Receptor-2 (HER-2) using carbodiimide chemistry. The uptake of antibody conjugated ICG-DOX-PLGA nanoparticles (AIDNP) was enhanced in SKOV-3 (HER-2 overexpressing cell lines) compared to their non-conjugated counterparts (ICG-DOX-PLGA nanoparticles (IDNP)). The uptake of antibody conjugated ICG-DOX-PLGA nanoparticles, however, was similar in MES-SA and MES-SA/Dx5 cancer cells (HER-2 negative cell lines), which were used as negative controls. The cytotoxicity results after laser treatment (808 nm, 6.7 W/cm(2)) showed an enhanced toxicity in treatment of SKOV-3. The negative controls exhibited comparable cytotoxicity with or without exposure to the laser. Thus, this study showed that these antibody conjugated ICG-DOX-PLGA nanoparticles have potential for combinatorial chemotherapy and hyperthermia.


Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Antibodies, Monoclonal/administration & dosage , Doxorubicin/administration & dosage , Indocyanine Green/administration & dosage , Laser Therapy , Nanoparticles/administration & dosage , Antibiotics, Antineoplastic/chemistry , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/immunology , Cell Line, Tumor , Cell Survival/drug effects , Doxorubicin/chemistry , Humans , Indocyanine Green/chemistry , Lactic Acid/chemistry , Nanoparticles/chemistry , Polyglycolic Acid/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer , Receptor, ErbB-2/immunology
13.
Beilstein J Nanotechnol ; 5: 313-22, 2014.
Article in English | MEDLINE | ID: mdl-24778954

ABSTRACT

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.

14.
J Photochem Photobiol B ; 119: 52-9, 2013 Feb 05.
Article in English | MEDLINE | ID: mdl-23347965

ABSTRACT

This study reports the preparation and characterization of IR820-chitosan conjugates that have potential multifunctional imaging-hyperthermia applications in cancer. The conjugates were formulated by covalentcouplingofchitosan to a carboxyl derivatized IR820, and studied for optical imaging and hyperthermia applications. IR820-chitosan conjugates were able to generate heat upon exposure to 808nm laser and produce hyperthermic cell growth inhibition in cancer cell lines MES-SA, SKOV-3 and Dx5. The level of cell growth inhibition caused by hyperthermia was significantly higher for IR820-chitosan compared to IR820 in MES-SA and Dx5 cells. Fluorescent microscope images of these cancer cell lines after 3-h exposure to 5µM IR820-chitosan showed that the conjugates can be used for in vitro near-infrared imaging. In an in vivo rat model, the conjugates accumulated in the liver after i.v. injection and were excreted through the gastrointestinal tract, demonstrating a different biodistribution when compared to the free dye. The accumulation of these conjugates in bile with subsequent gastrointestinal excretion allows for potential applications as gastrointestinal contrast agents and delivery vehicles. This formulation can potentially be used in multifunctional cancer theranostics.


Subject(s)
Chitosan/chemistry , Chitosan/pharmacokinetics , Hyperthermia, Induced/methods , Indocyanine Green/analogs & derivatives , Microscopy, Fluorescence/methods , Neoplasms/therapy , Absorption , Animals , Cell Line, Tumor , Chitosan/administration & dosage , Contrast Media/pharmacokinetics , Drug Screening Assays, Antitumor , Feces , Female , Fluorescent Dyes/chemistry , Fluorescent Dyes/pharmacokinetics , Humans , Indocyanine Green/administration & dosage , Indocyanine Green/chemistry , Indocyanine Green/pharmacokinetics , Infrared Rays , Injections, Intravenous , Liver/drug effects , Neoplasms/pathology , Rats , Rats, Inbred F344 , Spectroscopy, Fourier Transform Infrared
15.
J Biomed Nanotechnol ; 8(4): 686-94, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22852478

ABSTRACT

Novel IR820-polyethylene glycol-diamine nanoplexes (IR820-PDNCs) have potential multifunctional imaging-hyperthermia applications in cancer. Nanoplexes were formulated by ionic interaction and characterized in vitro for their imaging and hyperthermia capabilities. The resulting nanoplexes were approximately 50 nm diameter, with a zeta potential of 2.0 +/- 0.9 mV, and able to generate heat upon exposure to 808 nm laser. Cytotoxicity studies in SKOV-3, MES-SA and Dx5 cancer cell lines demonstrate comparable cytotoxicity of IR820-PDNCs versus free IR820 after 24 hours. The nanoplexes are able to produce hyperthermic cell growth inhibition in all three cancer cell lines after excitation with laser. The level of cell growth inhibition caused by hyperthermia is significantly higher for IR820-PDNCs compared to IR820 in MES-SA and Dx5 cells. Fluorescent microscope images after 2.5-hour exposure to 5 microM IR820-PDNCs or 5 microM free IR820 show increased uptake for IR820-PDNCs compared to free IR820, especially for SKOV-3 and Dx5 cancer cells. This formulation can potentially be used in multifunctional cancer theranostics.


Subject(s)
Heterocyclic Compounds, 3-Ring/chemistry , Heterocyclic Compounds, 3-Ring/pharmacology , Hyperthermia, Induced/methods , Nanofibers/chemistry , Polyethyleneimine/analogs & derivatives , Cell Death/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Coloring Agents/chemistry , Female , Humans , Ovarian Neoplasms/pathology , Ovarian Neoplasms/therapy , Polyethyleneimine/chemistry , Polyethyleneimine/pharmacology , Sarcoma/pathology , Sarcoma/therapy , Staining and Labeling/methods , Uterine Neoplasms/pathology , Uterine Neoplasms/therapy
16.
Mol Imaging ; 11(2): 99-113, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22469238

ABSTRACT

AbstractNear-infrared (NIR) fluorophores are the focus of extensive research for combined molecular imaging and hyperthermia. In this study, we showed that the cyanine dye IR820 has optical and thermal generation properties similar to those of indocyanine green (ICG) but with improved in vitro and in vivo stability. The fluorescent emission of IR820 has a lower quantum yield than ICG but less dependence of the emission peak location on concentration. IR820 demonstrated degradation half-times approximately double those of ICG under all temperature and light conditions in aqueous solution. In hyperthermia applications, IR820 generated lower peak temperatures than ICG (4-9%) after 3-minute laser exposure. However, there was no significant difference in hyperthermia cytotoxicity, with both dyes causing significant cell growth inhibition at concentrations ≥ 5 µM. Fluorescent images of cells with 10 µM IR820 were similar to ICG images. In rats, IR820 resulted in a significantly more intense fluorescence signal and significantly higher organ dye content than for ICG 24 hours after intravenous dye administration (p < .05). Our study shows that IR820 is a feasible agent in experimental models of imaging and hyperthermia and could be an alternative to ICG when greater stability, longer image collection times, or more predictable peak locations are desirable.


Subject(s)
Hot Temperature , Indocyanine Green/analogs & derivatives , Indocyanine Green/chemistry , Light , Abdomen , Animals , Cell Death/drug effects , Cell Line, Tumor , Humans , Hyperthermia, Induced , Indocyanine Green/administration & dosage , Indocyanine Green/toxicity , Injections, Intravenous , Organ Specificity/drug effects , Rats , Rats, Wistar , Solutions , Solvents , Spectrometry, Fluorescence , Spectroscopy, Near-Infrared , Time Factors
17.
Appl Biochem Biotechnol ; 165(7-8): 1628-51, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21947761

ABSTRACT

Successful cancer management depends on accurate diagnostics along with specific treatment protocols. Current diagnostic techniques need to be improved to provide earlier detection capabilities, and traditional chemotherapy approaches to cancer treatment are limited by lack of specificity and systemic toxicity. This review highlights advances in nanotechnology that have allowed the development of multifunctional platforms for cancer detection, therapy, and monitoring. Nanomaterials can be used as MRI, optical imaging, and photoacoustic imaging contrast agents. When used as drug carriers, nanoformulations can increase tumor exposure to therapeutic agents and result in improved treatment effects by prolonging circulation times, protecting entrapped drugs from degradation, and enhancing tumor uptake through the enhanced permeability and retention effect as well as receptor-mediated endocytosis. Multiple therapeutic agents such as chemotherapy, antiangiogenic, or gene therapy agents can be simultaneously delivered by nanocarriers to tumor sites to enhance the effectiveness of therapy. Additionally, imaging and therapy agents can be co-delivered to provide seamless integration of diagnostics, therapy, and follow-up, and different therapeutic modalities such as chemotherapy and hyperthermia can be co-administered to take advantage of synergistic effects. Liposomes, metallic nanoparticles, polymeric nanoparticles, dendrimers, carbon nanotubes, and quantum dots are examples of nanoformulations that can be used as multifunctional platforms for cancer theranostics. Nanomedicine approaches in cancer have great potential for clinically translatable advances that can positively impact the overall diagnostic and therapeutic process and result in enhanced quality of life for cancer patients. However, a concerted scientific effort is still necessary to fully explore long-term risks, effects, and precautions for safe human use.


Subject(s)
Drug Delivery Systems/instrumentation , Nanomedicine/instrumentation , Nanostructures/chemistry , Neoplasms/diagnosis , Neoplasms/drug therapy , Ultrasonography/instrumentation , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Drug Delivery Systems/methods , Humans , Nanomedicine/methods , Neoplasms/diagnostic imaging , Ultrasonography/methods
18.
Nanomedicine ; 7(3): 324-32, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21094277

ABSTRACT

The purpose of this study was to compare the cellular uptake and cytotoxicity of targeted and nontargeted doxorubicin (DOX)-loaded poly(d,l-lactide co-glycolide) (PLGA) nanoparticle (NP) drug delivery systems in drug-resistant ovarian (SKOV-3) and uterine (MES-SA/Dx5) cancer cell lines. The cellular uptakes of DOX from nonconjugated DOX-loaded NPs (DNPs) and from HER-2 antibody-conjugated DOX-loaded NPs (ADNPs) in MES-SA/Dx5 cancer cells were higher compared to free DOX. Results also showed higher uptake of DOX from ADNPs in SKOV-3 cells compared with both free DOX and DNPs treatment. Cytotoxicity results at 10 µM extracellular DOX concentration were consistent with the cellular uptake results. Our study concludes that cellular uptake and cytotoxicity of DOX can be improved in MES-SA/Dx5 cells by loading DOX into PLGA NPs. DNPs targeted to membrane receptors may enhance cellular uptake and cytotoxicity in SKOV-3 cells. FROM THE CLINICAL EDITOR: The authors of this study compare the cellular uptake and cytotoxicity of targeted and nontargeted doxorubicin loaded PLGA nanoparticle delivery systems in drug-resistant ovarian and uterine cancer cell lines, concluding that cellular uptake and cytotoxicity of doxorubicin can be improved by the proposed methods.


Subject(s)
Drug Carriers/toxicity , Drug Resistance, Neoplasm/drug effects , Endocytosis/drug effects , Antibodies/immunology , Biological Transport/drug effects , Cell Death/drug effects , Cell Line, Tumor , Chemistry, Pharmaceutical , Doxorubicin/pharmacology , Humans , Intracellular Space/drug effects , Intracellular Space/metabolism , Kinetics , Light , Microscopy, Confocal , Nanoparticles/chemistry , Particle Size , Scattering, Radiation , Static Electricity , Subcellular Fractions/metabolism
19.
Pharm Res ; 27(10): 2242-53, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20694526

ABSTRACT

PURPOSE: To test the effectiveness of a dual-agent-loaded PLGA nanoparticulate drug delivery system containing doxorubicin (DOX) and indocyanine green (ICG) in a DOX-sensitive cell line and two resistant cell lines that have different resistance mechanisms. METHODS: The DOX-sensitive MES-SA uterine sarcoma cell line was used as a negative control. The two resistant cell lines were uterine sarcoma MES-SA/Dx5, which overexpresses the multidrug resistance exporter P-glycoprotein, and ovarian carcinoma SKOV-3, which is less sensitive to doxorubicin due to a p53 gene mutation. The cellular uptake, subcellular localization and cytotoxicity of the two agents when delivered via nanoparticles (NPs) were compared to their free-form administration. RESULTS: The cellular uptake and cytotoxicity of DOX delivered by NPs were comparable to the free form in MES-SA and SKOV-3, but much higher in MES-SA/Dx5, indicating the capability of the NPs to overcome P-glycoprotein resistance mechanisms. NP-encapsulated ICG showed slightly different subcellular localization, but similar fluorescence intensity when compared to free ICG, and retained the ability to generate heat for hyperthermia delivery. CONCLUSION: The dual-agent-loaded system allowed for the simultaneous delivery of hyperthermia and chemotherapy, and this combinational treatment greatly improved cytotoxicity in MES-SA/Dx5 cells and to a lesser extent in SKOV-3 cells.


Subject(s)
Antineoplastic Agents/administration & dosage , Doxorubicin/administration & dosage , Drug Carriers/chemistry , Lactic Acid/chemistry , Nanoparticles/chemistry , Organic Chemicals/administration & dosage , Polyglycolic Acid/chemistry , Antineoplastic Agents/pharmacokinetics , Biological Transport , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Doxorubicin/pharmacokinetics , Doxorubicin/pharmacology , Drug Resistance, Neoplasm/drug effects , Female , Humans , Hyperthermia, Induced/methods , Microscopy, Electron, Scanning , Optical Phenomena , Organic Chemicals/pharmacokinetics , Organic Chemicals/pharmacology , Particle Size , Polylactic Acid-Polyglycolic Acid Copolymer , Solubility , Surface Properties
20.
Biomaterials ; 31(23): 6069-74, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20488532

ABSTRACT

Biomimetic nanoparticles based on polysaccharides-poly(alkylcyanoacrylates) copolymers were initially developed in view of drug delivery. Core-shell nanoparticles covered with a sufficiently long brush of polysaccharides were shown to be very low complement activators and have the potential for long circulation times in the bloodstream. Such nanoparticles bearing haemoglobin were envisaged as potential red cell substitutes. Different core-shell nanoparticles with a brush shell made of dextran, dextran-sulphate, or heparin were prepared and haemoglobin (Hb) could be adsorbed on their surface. Benzene tetracarboxylic acid (BTCA) was used as a coupling agent for Hb to dextran-coated nanoparticles; the Hb loading capacity of the dextran nanoparticles showed a 9.3 fold increased. The coupled Hb maintained the allosteric properties of free Hb. While modification of nanoparticles by BTCA slightly increased complement activation, the further addition of Hb totally reversed this effect providing Hb-loaded nanoparticles with a very low level of complement activation. Such nanoparticles could be a suitable alternative to haemoglobin solutions in the development of a blood substitute.


Subject(s)
Cyanoacrylates/chemistry , Nanoparticles , Oxygen/administration & dosage , Polymers/chemistry , Polysaccharides/chemistry
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