scholarly journals Galactosamine-Conjugating Zwitterionic Block Copolymer for Reduction-Responsive Release and Active Targeted Delivery of Doxorubicin to Hepatic Carcinoma Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Jingming Zhai ◽  
Biyu Zhou ◽  
Yanhui An ◽  
Binzhong Lu ◽  
Yonggang Fan ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Targeted Delivery ◽  
Polymeric Micelles ◽  
Specific Binding ◽  
Drug Carrier ◽  
Polymeric Micelle ◽  
Carcinoma Cells ◽  
Active Targeting ◽  
Hepatic Carcinoma

Nanocarriers with integrated advantage, such as excellent stealth property, active targeting function, and rapid intracellular drug release, are significant for cancer treatment. Herein, a biodegradable zwitterionic triblock copolymer containing disulfide-linked poly-ε-caprolactone and polycarboxybetaine methacrylate (PCB-SS-PCL-SS-PCB) was first synthesized and then partly modified with galactosamine (GAL) for constructing polymeric micelle drug carrier with multifunctionality. Polymeric micelles showed ultralow protein absorption in serum and obvious reduction-responsiveness in the presence of glutathione, provided by the zwitterionic polymer shell and the disulfide bond, respectively. Furthermore, active targeting of the carrier to hepatic carcinoma cells was achieved via GAL ligands on PCB shells due to their specific binding to asialoglycoprotein receptors on the cell surface. As expected, in vivo competition studies demonstrated that doxorubicin- (DOX-) loaded GAL-modified micelles have better anticancer effect in hepatic tumor-bearing mice than free DOX and nontargetable micelles. As a result, this novel multifunctional carrier provides a valuable strategy to design promising anticancer drug delivery systems for liver cancer treatment.

scholarly journals NIR Light-Triggered Chemo-Phototherapy by ICG Functionalized MWNTs for Synergistic Tumor-Targeted Delivery

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2145
Author(s):  
Lu Tang ◽  
Aining Zhang ◽  
Yijun Mei ◽  
Qiaqia Xiao ◽  
Xiangting Xu ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Targeted Delivery ◽  
Near Infrared ◽  
Drug Carrier ◽  
Tumor Growth Inhibition ◽  
In Vivo Experiments ◽  
Promising Application ◽  
Targeting Ability

The combinational application of photothermal therapy (PTT), chemotherapy, and nanotechnology is a booming therapeutic strategy for cancer treatment. Multi-walled carbon nanotube (MWNT) is often utilized as drug carrier in biomedical fields with excellent photothermal properties, and indocyanine green (ICG) is a near-infrared (NIR) dye approved by FDA. In addition, ICG is also a photothermal agent that can strongly absorb light energy for tumor ablation. Herein, we explored a synergistic strategy by connecting MWNT and a kind of ICG derivate ICG-NH2 through hyaluronic acid (HA) that possesses CD44 receptor targeting ability, which largely enhanced the PTT effect of both MWNT and ICG-NH2. To realize the synergistic therapeutic effect of chemotherapy and phototherapy, doxorubicin (DOX) was attached on the wall of MWNT via π–π interaction to obtain the final MWNT-HA-ICG/DOX nanocomplexes. Both in vitro and in vivo experiments verified the great therapeutic efficacy of MWNT-HA-ICG/DOX nanocomplexes, which was characterized by improved photothermal performance, strengthened cytotoxicity, and elevated tumor growth inhibition based on MCF-7 tumor models. Therefore, this synergistic strategy we report here might offer a new idea with promising application prospect for cancer treatment.

Novel Mitochondrial Targeting Multifunctional Surface Charge-Reversal Polymeric Nanoparticles for Cancer Treatment

2019 ◽  
Vol 15 (11) ◽  
pp. 2151-2163 ◽  
Author(s):  
Lei Fang ◽  
Huaying Fan ◽  
Chunjing Guo ◽  
Linhan Cui ◽  
Peng Zhang ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Targeted Delivery ◽  
Polymeric Nanoparticles ◽  
In Vitro Cytotoxicity ◽  
Hydrodynamic Diameter ◽  
Mitochondrial Targeting ◽  
Anticancer Activities ◽  
Charge Reversal

Polymeric nanoparticles were widely used as delivery vehicles for targeted delivery of anticancer drugs, because of their targeting property and versatility. Mitochondria are one of the important organelles that regulate the apoptosis of cancer cells and can be considered as a pivotal target for cancer treatment. A pH-responsive charge-reversal and mitochondrial targeting nanoparticles, Vitamin B6-oligomeric hyaluronic acid-dithiodipropionic acid-berberine (B6-oHA-SS-Ber), were prepared in this study. Ber is a lipophilic cation that was conjugated with oHA through disulfide bonds to produce mitochondria-targeted conjugates (oHA-SS-Ber). B6 was conjugated to oHA to obtain B6-oHA-SS-Ber and the two types of Cur-loaded nanoparticles (Cur-NPs) were formulated by the dialysis method. Due to pKa of B6, the charge they carried in the tumor tissue acidic microenvironment can be transferred from negative charge to positive charge, further targeting mitochondria. In our study, we successfully synthesized B6-HA-SS-Ber and characterized the structure by 1H-NMR. According to the results of transmission electron microscopy (TEM), we found that the B6-oHA-SS-Ber/Cur micelles could self-assembled in water to form spherical nanoparticles, with a hydrodynamic diameter of 172.9±13 nm. Moreover, in vitro cytotoxicity, cellular uptake, lysosome escape and mitochondrial distribution researches revealed the better effect of B6-oHA-SS-Ber/Cur micelles in comparison to oHA-SS-Ber/Cur. In vivo anticancer activities indicated that the B6-oHA-SS-Ber/Cur micelles exhibited effective inhibition of tumor growth.

scholarly journals Gold Nanoparticle-Based Fluorescent Theranostics for Real-Time Image-Guided Assessment of DNA Damage and Repair

2019 ◽  
Vol 20 (3) ◽  
pp. 471 ◽  
Author(s):  
Shriya S. Srinivasan ◽  
Rajesh Seenivasan ◽  
Allison Condie ◽  
Stanton L. Gerson ◽  
Yanming Wang ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Real Time ◽  
Targeted Delivery ◽  
Specific Binding ◽  
Imaging Techniques ◽  
Cancer Cell Line ◽  
Molecular Probe ◽  
Biodistribution Studies

Chemotherapeutic dosing, is largely based on the tolerance levels of toxicity today. Molecular imaging strategies can be leveraged to quantify DNA cytotoxicity and thereby serve as a theranostic tool to improve the efficacy of treatments. Methoxyamine-modified cyanine-7 (Cy7MX) is a molecular probe which binds to apurinic/apyrimidinic (AP)-sites, inhibiting DNA-repair mechanisms implicated by cytotoxic chemotherapies. Herein, we loaded (Cy7MX) onto polyethylene glycol-coated gold nanoparticles (AuNP) to selectively and stably deliver the molecular probe intravenously to tumors. We optimized the properties of Cy7MX-loaded AuNPs using optical spectroscopy and tested the delivery mechanism and binding affinity using the DLD1 colon cancer cell line in vitro. A 10:1 ratio of Cy7MX-AuNPs demonstrated a strong AP site-specific binding and the cumulative release profile demonstrated 97% release within 12 min from a polar to a nonpolar environment. We further demonstrated targeted delivery using imaging and biodistribution studies in vivo in an xenografted mouse model. This work lays a foundation for the development of real-time molecular imaging techniques that are poised to yield quantitative measures of the efficacy and temporal profile of cytotoxic chemotherapies.

scholarly journals Bioequivalence Assessment of High-Capacity Polymeric Micelle Nanoformulation of Paclitaxel and Abraxane® in Rodent and Non-Human Primate Models Using a Stable Isotope Tracer Assay

2021 ◽  
Author(s):  
Duhyeong Hwang ◽  
Natasha Vinod ◽  
Sarah L. Skoczen ◽  
Jacob D. Ramsey ◽  
Kelsie S. Snapp ◽  
...  
Keyword(s):  
Stable Isotope ◽  
Drug Exposure ◽  
Polymeric Micelles ◽  
Clinical Investigation ◽  
Rhesus Macaques ◽  
Physicochemical Characterization ◽  
Polymeric Micelle ◽  
Stable Isotope Tracer ◽  
Isotope Tracer

AbstractThe in vivo fate of nanoformulated drugs is governed by the physicochemical properties of the drug and the functionality of nanocarriers. Nanoformulations such as polymeric micelles, which physically encapsulate poorly soluble drugs, release their payload into the bloodstream during systemic circulation. This results in three distinct fractions of the drug-nanomedicine: encapsulated, protein-bound, and free drug. Having a thorough understanding of the pharmacokinetic (PK) profiles of each fraction is essential to elucidate mechanisms of nanomedicine-driven changes in drug exposure and PK/PD relationships pharmacodynamic activity. Here, we present a comprehensive preclinical assessment of the poly(2-oxazoline)-based polymeric micelle of paclitaxel (PTX) (POXOL hl-PM), including bioequivalence comparison to the clinically approved paclitaxel nanomedicine, Abraxane®. Physicochemical characterization and toxicity analysis of POXOL hl-PM was conducted using standardized protocols by the Nanotechnology Characterization Laboratory (NCL). The bioequivalence of POXOL hl-PM to Abraxane® was evaluated in rats and rhesus macaques using the NCL’s established stable isotope tracer ultrafiltration assay (SITUA) to delineate the plasma PK of each PTX fraction. The SITUA study revealed that POXOL hl-PM and Abraxane® had comparable PK profiles not only for total PTX but also for the distinct drug fractions, suggesting bioequivalence in given animal models. The comprehensive preclinical evaluation of POXOL hl-PM in this study showcases a series of widely-applicable standardized studies by NCL for assessing nanoformulations prior to clinical investigation.GRAPHICAL ABSTRACT

scholarly journals Inulin-Grafted Stearate (In-g-St) as the Effective Self-Assembling Polymeric Micelle: Synthesis and Evaluation for the Delivery of Betamethasone

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Gholamabbas Chehardoli ◽  
Parham Norouzian ◽  
Farzin Firozian
Keyword(s):  
Zeta Potential ◽  
Sustained Release ◽  
Targeted Delivery ◽  
Encapsulation Efficiency ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Polymeric Micelle ◽  
Water Soluble ◽  
Burst Release ◽  
Potential Measurement

Background. Betamethasone as a corticosteroid drug is commonly used for the treatment of rheumatoid arthritis. Unfortunately, betamethasone is a low water-soluble drug and its efficacy is low. So an attractive strategy is the targeted delivery of betamethasone to the damaged joint using polymeric micelle-based carriers. Methods. Inulin-grafted stearate (In-g-St) was synthesized via the reaction of stearoyl chloride and inulin, then characterized by FT-IR and H-NMR. In-g-St forms micelles in the presence of betamethasone. The prepared polymeric micelles were characterized for size, zeta potential, drug loading, particles’ morphology, critical micelle concentration (CMC), and encapsulation efficiency. So sustained release polymeric micelles of betamethasone were developed by employing In-g-St. Results. The measurement of particle size showed a mean diameter of 60 and 130 nm for 10% and 20% drug-loaded micelles, respectively, and SEM showed that the particle’s morphologies are spherical. Zeta potential measurement for the drug-containing micelles showed a value of -11.8 mV. Drug loading efficiency and the encapsulation efficiency were 6.36% and 63.6%, as well as 18.97% and 94.88% for 10% and 20%, respectively. 20% drug-loaded polymer showed a small burst release of betamethasone at the first 3 h which was followed by sustained release in the next 24 h. Furthermore, the formula with 10% exhibited good sustained release properties except for the minor initial burst release. Conclusion. Data from the zeta potential, CMC, drug loading capacity, and in vitro drug release studies indicated that In-g-St polymeric micelles can be suitable candidates for the efficient delivery of hydrophobic drugs like betamethasone.

scholarly journals Intravitreal Polymeric Nanocarriers with Long Ocular Retention and Targeted Delivery to the Retina and Optic Nerve Head Region

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 445
Author(s):  
Vijayabhaskarreddy Junnuthula ◽  
Amir Sadeghi Boroujeni ◽  
Shoupeng Cao ◽  
Shirin Tavakoli ◽  
Roxane Ridolfo ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Optic Nerve ◽  
Targeted Delivery ◽  
Polymeric Micelles ◽  
Umbilical Vein ◽  
Gel Permeation Chromatography ◽  
Single Particle Tracking ◽  
Trimethylene Carbonate ◽  
Head Region

Posterior eye tissues, such as retina, are affected in many serious eye diseases, but drug delivery to these targets is challenging due to various anatomical eye barriers. Intravitreal injections are widely used, but the intervals between invasive injections should be prolonged. We synthesized and characterized (1H NMR, gel permeation chromatography) block copolymers of poly(ethylene glycol), poly(caprolactone), and trimethylene carbonate. These polymers self-assembled to polymersomes and polymeric micelles. The mean diameters of polymersomes and polymeric micelles, about 100 nm and 30–50 nm, respectively, were obtained with dynamic light scattering. Based on single particle tracking and asymmetric flow field-flow fractionation, the polymeric micelles and polymersomes were stable and diffusible in the vitreous. The materials did not show cellular toxicity in cultured human umbilical vein endothelial cells in the Alamar Blue Assay. Pharmacokinetics of the intravitreal nanocarriers in the rabbits were evaluated using in vivo fluorophotometry. The half-lives of the polymersomes (100 nm) and the micelles (30 nm) were 11.4–32.7 days and 4.3–9.5 days. The intravitreal clearance values were 1.7–8.7 µL/h and 3.6–5.4 µL/h for polymersomes and polymeric micelles, respectively. Apparent volumes of distribution of the particles in the rabbit vitreous were 0.6–1.3 mL for polymeric micelles and 1.9–3.4 mL for polymersomes. Polymersomes were found in the vitreous for at least 92 days post-dosing. Furthermore, fundus imaging revealed that the polymersomes accumulated near the optic nerve and retained there even at 111 days post-injection. Polymersomes represent a promising technology for controlled and site-specific drug delivery in the posterior eye segment.

Real-time monitoring of a controlled drug delivery system in vivo: construction of a near infrared fluorescence monomer conjugated with pH-responsive polymeric micelles

2016 ◽  
Vol 4 (19) ◽  
pp. 3377-3386 ◽  
Author(s):  
Li Chen ◽  
Bizheng Chen ◽  
Xiaodong Liu ◽  
Yujie Xu ◽  
Lifen Zhang ◽  
...  
Keyword(s):  
Real Time ◽  
Near Infrared ◽  
Polymeric Micelles ◽  
Controlled Drug Delivery ◽  
Polymeric Micelle ◽  
Amphiphilic Copolymer ◽  
Tumor Site ◽  
Ph Responsive ◽  
Controlled Drug Delivery System

A self-assembled polymeric micelle from multifunctional amphiphilic copolymer with NIR and pH-sensitive groups can be used to monitor the dynamic process of its arriving at the tumor site in real time.

scholarly journals Targeted Delivery of siRNA through Nanocomplex using Specific Fusion Peptides for Breast Cancer Treatment

2021 ◽  
Author(s):  
Jang Hyuk Bang ◽  
Kyung Ah Kim ◽  
Yeong Chae Ryu ◽  
Byoung Choul Kim ◽  
BYEONG HEE HWANG
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Cellular Uptake ◽  
Targeted Delivery ◽  
Small Rnas ◽  
Sirna Delivery ◽  
Fusion Peptides ◽  
Breast Cancer Cell Growth

Breast cancer is one of the serious diseases and has the second-highest mortality in women worldwide. RNA interference has been developed as a promising way of specific cancer treatment by silencing oncogenes efficiently. However, small RNAs exhibits difficulties in specific cellular uptake and instability. Therefore, we designed novel fusion peptides (RS and RT) for an efficient, stable, and specific delivery of small RNAs. Both RS and RT peptides could form self-assembled nanocomplexes via electrostatic attraction. RS nanocomplexes exhibited prolonged stability, enhanced cellular uptake, and target gene silencing by siRNAs to MDA-MB-231 breast cancer cells. Moreover, RS nanocomplexes successfully inhibited breast cancer cell growth via specific and efficient siRNA delivery. Furthermore, in vitro and in vivo safety tests showed negligible cytotoxicity and neither tissue damage nor significant inflammatory cytokine release. Therefore, the RS nanocomplexes could be expected to become a promising siRNA delivery platform for the treatment of breast cancer or other cancers.

In Vitro and In Vivo Characterization of Various Ferrites for Hyperthermia in Cancer-Treatment

2005 ◽  
Vol 284-286 ◽  
pp. 827-830
Author(s):  
D.H. Kim ◽  
Se Ho Lee ◽  
Kyoung Nam Kim ◽  
Kwang Mahn Kim ◽  
I.B. Shim ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Cancer Treatment ◽  
Carcinoma Cells ◽  
Alternating Magnetic Field ◽  
Normal Cells ◽  
Tumor Bearing ◽  
In Vivo Characterization

Ceramic ferrites can be used to cancer-treatment. Heating of certain organs or tissue up to temperature between 42oC and 45oC preferentially for cancer therapy is called hyperthermia. We synthesized ferrites with various compositions in the system Co1-xNixFe2O4 as hyperthermic thermoseed in cancer-treatment and evaluated their effects on the necrosis of cancer cells under alternating magnetic field in vivo as well as in vitro. When a CoFe2O4 was placed into 0.2 ml distilled water, the greatest temperature change in this study, Δ T=29.3oC, was observed. More than half of the carcinoma cells were dead after exposure to alternating magnetic field using CoFe2O4, while normal cells were survived more than 60%. The injection of this ferrite particles into the tumor bearing mice was able to suppress the number and volume of tumors. CoFe2O4 is expected the useful hyperthermic thermoseed in cancer-treatment because it exhibited the greatest necrosis of carcinoma cells in vitro and in vivo.

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