Norepinephrine transporter analog benzylguanidine-conjugated nanoparticles for the delivery of paclitaxel in neuroblastoma

Nanomedicine ◽  
2021 ◽  
Author(s):  
Ozlem Ozen Karakus ◽  
Kavitha Godugu ◽  
Taher Salaheldin ◽  
Kazutoshi Fujioka ◽  
Shaker A Mousa
Keyword(s):  
Polyethylene Glycol ◽  
Targeted Delivery ◽  
Chemotherapeutic Agent ◽  
Norepinephrine Transporter ◽  
Neuroendocrine Cells ◽  
Safe Delivery ◽  
Targeted Nanoparticles ◽  
Chemotherapy Agent ◽  
Neuroblastoma Tumor ◽  
Targeted Agent

Aim: We previously synthesized a polyethylene glycol-based norepinephrine transporter-targeted agent, BG-P-TAT, which has a benzylguanidine and a triazolyl-tetrac group. This targeted conjugate showed suppression of neuroblastoma tumor progression. In this study we aimed to synthesize nanoparticles to encapsulate the chemotherapeutic agent paclitaxel for targeting neuroblastoma tumors by using benzylguanidine so that it can compete with norepinephrine for uptake by neuroendocrine cells. Methods: Biocompatible poly(lactide-co-glycolic acid)-polyethylene glycol was chosen to prepare targeted nanoparticles for safe delivery of the chemotherapy agent paclitaxel. Result: Paclitaxel concentration was 60% higher in neuroblastoma tumors of mice treated with paclitaxel encapsulated in targeted nanoparticles than with non-targeted nanoparticles. Conclusion: These findings support the targeted delivery of paclitaxel as a chemotherapeutic agent for neuroblastoma.

scholarly journals Modified Gold Nanoparticles for Efficient Delivery of Betulinic Acid to Cancer Cell Mitochondria

2021 ◽  
Vol 22 (10) ◽  
pp. 5072
Author(s):  
Olakunle Oladimeji ◽  
Jude Akinyelu ◽  
Aliscia Daniels ◽  
Moganavelli Singh
Keyword(s):  
Polyethylene Glycol ◽  
Cancer Cell ◽  
Betulinic Acid ◽  
Targeted Delivery ◽  
Epigallocatechin Gallate ◽  
High Amplitude ◽  
Significant Inhibition ◽  
Mitochondrial Targeting ◽  
The Impact

Advances in nanomedicine have seen the adaptation of nanoparticles (NPs) for subcellular delivery for enhanced therapeutic impact and reduced side effects. The pivotal role of the mitochondria in apoptosis and their potential as a target in cancers enables selective induction of cancer cell death. In this study, we examined the mitochondrial targeted delivery of betulinic acid (BA) by the mitochondriotropic TPP+-functionalized epigallocatechin gallate (EGCG)-capped gold NPs (AuNPs), comparing the impact of polyethylene glycol (PEG) and poly-L-lysine-graft-polyethylene glycol (PLL-g-PEG) copolymer on delivery efficacy. This included the assessment of their cellular uptake, mitochondrial localization and efficacy as therapeutic delivery platforms for BA in the human Caco-2, HeLa and MCF-7 cancer cell lines. These mitochondrial-targeted nanocomplexes demonstrated significant inhibition of cancer cell growth, with targeted nanocomplexes recording IC50 values in the range of 3.12–13.2 µM compared to that of the free BA (9.74–36.31 µM) in vitro, demonstrating the merit of mitochondrial targeting. Their mechanisms of action implicated high amplitude mitochondrial depolarization, caspases 3/7 activation, with an associated arrest at the G0/G1 phase of the cell cycle. This nano-delivery system is a potentially viable platform for mitochondrial-targeted delivery of BA and highlights mitochondrial targeting as an option in cancer therapy.

scholarly journals An Update on Mesoporous Silica Nanoparticle Applications in Nanomedicine

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1067
Author(s):  
Elham Rastegari ◽  
Yu-Jer Hsiao ◽  
Wei-Yi Lai ◽  
Yun-Hsien Lai ◽  
Tien-Chun Yang ◽  
...  
Keyword(s):  
Mesoporous Silica ◽  
Targeted Delivery ◽  
Mesoporous Silica Nanoparticles ◽  
Silica Nanoparticle ◽  
Molecular Structures ◽  
Cancer Therapies ◽  
Safe Delivery ◽  
Therapeutic Drugs ◽  
Therapeutic Benefits

The efficient and safe delivery of therapeutic drugs, proteins, and nucleic acids are essential for meaningful therapeutic benefits. The field of nanomedicine shows promising implications in the development of therapeutics by delivering diagnostic and therapeutic compounds. Nanomedicine development has led to significant advances in the design and engineering of nanocarrier systems with supra-molecular structures. Smart mesoporous silica nanoparticles (MSNs), with excellent biocompatibility, tunable physicochemical properties, and site-specific functionalization, offer efficient and high loading capacity as well as robust and targeted delivery of a variety of payloads in a controlled fashion. Such unique nanocarriers should have great potential for challenging biomedical applications, such as tissue engineering, bioimaging techniques, stem cell research, and cancer therapies. However, in vivo applications of these nanocarriers should be further validated before clinical translation. To this end, this review begins with a brief introduction of MSNs properties, targeted drug delivery, and controlled release with a particular emphasis on their most recent diagnostic and therapeutic applications.

MICROFABRICATED ORAL DRUG DELIVERY SYSTEMS

INDIAN DRUGS ◽  
2015 ◽  
Vol 52 (11) ◽  
pp. 5-13
Author(s):  
A Shetty ◽  
◽  
G Srinivasan
Keyword(s):  
Drug Delivery ◽  
Integrated Circuit ◽  
Targeted Delivery ◽  
Microelectromechanical Systems ◽  
Film Growth ◽  
Oral Drug Delivery ◽  
Complete Solution ◽  
Oral Drug ◽  
Safe Delivery ◽  
Multiple Drugs

Microfabrication is a collection of techniques developed to fabricate micron sized features, best suited to develop the novel drug delivery microdevices. microfabrication techniques were originally developed in the microelectronics industry to produce functional devices on the micron scale such as sensors, switches, filters and gears. Approaches like modification of drug itself to improve its permeability/ solubility characters, encapsulation techniques using micro/nanoparticles, use of protease inhibitors to curb proteolytic degradation, and use of intelligent polymers and hydrogels do not offer a complete solution for adequate and safe delivery of drugs, vaccines, peptides, proteins and others. This technology has been applied to the successful fabrication of a variety of implantable and oral drug delivery devices based on silicon, glass, silicone elastomer or plastic materials. These techniques that are utilized at present have developed as a result of integrated circuit manufacturing technologies, such as photolithography, thin film growth/deposition, etching and bonding. Micromachining allows for control over surface features, aspect ratio, particle size, shape and facilitating the development of an engineered particle for drug delivery that can incorporate the advantages of microparticles while avoiding their design flaws. It helps in multi-cell and multi-site attachment, multiple reservoirs of desired size to contain multiple drugs/biomolecules of interest. These fabrication techniques have led to the development of microelectromechanical systems (MEMS), bioMEMS, micro-total analysis systems (μ-TAS), lab-on-a-chip and other microdevices. Microfabricated devices are designed for uni-directional release, to prevent enzyme degradation, precise dosing and better patient compliance. Drug delivery in the form of microparticles and micropatches have been used for targeted delivery as well as in treatment of diseases like diabetes and cancer.

Transferrin-targeted poly(butylene adipate)/terephthalate nanoparticles for targeted delivery of 5-fluorouracil in HT29 colorectal cancer cell line

2017 ◽  
Vol 32 (5) ◽  
pp. 503-527 ◽  
Author(s):  
Jaleh Varshosaz ◽  
Sara Riahi ◽  
Erfaneh Ghassami ◽  
Ali Jahanian-Najafabadi
Keyword(s):  
Colorectal Cancer ◽  
Fourier Transform ◽  
Cell Line ◽  
Targeted Delivery ◽  
Fourier Transform Infrared ◽  
Colorectal Cancer Cell Line ◽  
Tween 20 ◽  
Ultraviolet Spectroscopy ◽  
Targeted Nanoparticles ◽  
Sds Page

The purpose of this study was to design 5-fluorouracil-loaded poly(butylene adipate)/terephthalate (Ecoflex®) nanoparticles for targeting colorectal cancer. The nanoparticles were prepared by emulsification–solvent evaporation method and optimized by a full factorial design. The effects of polymer and surfactant concentration, surfactant type, and stirrer rate were studied on the particle size, zeta potential, loading efficiency, and release efficiency of nanoparticles. For production of targeted nanoparticles, chitosan was conjugated to transferrin which was then coated on the surface of Ecoflex nanoparticles via electrostatic interactions. The conjugation of transferrin/chitosan was verified by Fourier transform infrared spectroscopy, ultraviolet spectroscopy, and SDS-PAGE (sodium dodecyl sulfate–polyacrylamide gel electrophoresis) methods and quantified by ultraviolet spectroscopy assay. The cytotoxicity of 5-fluorouracil loaded in targeted and non-targeted nanoparticles was studied on human colon adenocarcinoma  cell line (HT29), Michigan Cancer Foundation-7 (MCF-7), and human umbilical vein endothelial cells using MTT (thiazolyl blue tetrazolium bromide) assay. The best results were obtained from nanoparticles prepared by 0.2% of the polymer, 2% of Tween 20, and stirrer speed of 17,500 r/min. The successful conjugation of transferrin/chitosan was confirmed by Fourier transform infrared spectrum and SDS-PAGE results and was about 80%. The targeted nanoparticles showed significantly more cytotoxic effects on HT29 cells compared to free 5-fluorouracil and non-targeted nanoparticles. Blocking transferrin receptors resulted in a significantly higher cell survival for targeted nanoparticles which confirmed receptor-mediated cellular uptake of targeted nanoparticles.

scholarly journals Folate-polyethylene glycol conjugated carboxymethyl chitosan for tumor-targeted delivery of 5-fluorouracil

2014 ◽  
Vol 9 (3) ◽  
pp. 786-792 ◽  
Author(s):  
HAI-LANG LI ◽  
YA-XING HE ◽  
QIAN-HONG GAO ◽  
GUO-ZHONG WU
Keyword(s):  
Polyethylene Glycol ◽  
Targeted Delivery ◽  
Carboxymethyl Chitosan

Thyrointegrin αvβ3 nano targeted delivery of chemotherapy into solid tumors and its microenvironment.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14661-e14661
Author(s):  
Dhruba J. Bharali ◽  
Thangirala Institute Sudha ◽  
Kavitha Godugu ◽  
Noureldien H.E Darwish ◽  
Paul Joseph Davis ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Targeted Delivery ◽  
Chemotherapeutic Agent ◽  
Urinary Bladder Cancer ◽  
Chemotherapeutic Agents ◽  
Cell Surface Receptor ◽  
Human Pancreatic Cancer ◽  
Specific Cell ◽  
Αvβ3 Integrin ◽  
Animal Group

e14661 Background: Cancer cells and rapidly dividing endothelial cells relevant to tumors primarily express the αvβ3 integrin. Conjugation of tetraiodothyroacetic acid (tetrac) as diamino-tetrac to a poly (lactic-co-glycolic acid) (PLGA) polymer for the formation of Nano DAT was used to target a specific cell surface receptor on the αvβ3 integrin. PLGA prohibits cell entry and the nano shell could be loaded with a generic cancer chemotherapeutic. Without a payload, Nano DAT has anticancer and anti-angiogenesis properties. Methods: Xenografts of human urinary bladder cancer (263JBV) cells, human breast cancer (SUM149PT) cells, and human pancreatic cancer (SUIT-2) cells were established. Tumor growth and tumor content of cisplatin (263JBV xenografts), doxorubicin (SUM149PT xenografts), or of paclitaxel (SUIT-2 xenografts) were compared in the following daily treatment animal arms of cohorts for 3 weeks: (1) controls, (2) void PLGA Nanoparticle (NPs), (3) chemotherapeutic agent (cisplatin 1 mg/kg, doxorubicin 1 mg/kg, or paclitaxel 0.3 mg/kg), (4) Nano DAT 0.3 mg/kg, and (5) chemotherapeutic agent encapsulated into PLGA NPs and into Nano DAT. Results: Tumors in animals treated with Nano DAT bearing a payload of cisplatin, paclitaxel, or doxorubicin were associated with decreased tumor weight by 50%-60% (P < 0.01) with > 90% loss of cancer cell viability. Mean chemotherapeutic agents content of tumors (ng/gm of tissue) was 5-fold that of tumors from animals treated with chemotherapy, alone, and 3-fold that of tumors exposed to chemotherapy encapsulated into PLGA NPs, measured with an established LC/MS/MS method. Animals receiving cisplatin, alone, developed neurotoxicity (inability to use the hind limbs) in comparison to an animal group treated with Nano DAT bearing a payload of cisplatin, and was confirmed histopathologically. Conclusions: The payload capacity of Nano DAT for cancer chemotherapeutic agents and tumor-specific delivery of cancer chemotherapeutic agents significantly increases bladder, breast and pancreatic cancer content of, respectively, cisplatin and paclitaxel.

scholarly journals Tyrosinase Overexpression Promotes ATM-Dependent p53 Phosphorylation by Quercetin and Sensitizes Melanoma Cells to Dacarbazine

2008 ◽  
Vol 30 (5) ◽  
pp. 371-387
Author(s):  
Thilakavathy Thangasamy ◽  
Sivanandane Sittadjody ◽  
Kirsten H. Limesand ◽  
Randy Burd
Keyword(s):  
Low Dose ◽  
Tumor Response ◽  
Chemotherapeutic Agent ◽  
Response Rates ◽  
Melanoma Cells ◽  
High Dose ◽  
Ataxia Telangiectasia Mutated ◽  
Damage Response ◽  
Targeted Agent ◽  
Mutant Cells

Dacarbazine (DTIC) has been used for the treatment of melanoma for decades. However, monotherapy with this chemotherapeutic agent results only in moderate response rates. To improve tumor response to DTIC current clinical trials in melanoma focus on combining a novel targeted agent with chemotherapy. Here, we demonstrate that tyrosinase which is commonly overexpressed in melanoma activates the bioflavonoid quercetin (Qct) and promotes an ataxia telangiectasia mutated (ATM)-dependent DNA damage response. This response sensitizes melanoma cells that overexpress tyrosinase to DTIC. In DB-1 melanoma cells that overexpress tyrosinase (Tyr+ cells), the threshold for phosphorylation of ATM and p53 at serine 15 was observed at a low dose of Qct (25 μM) when compared to the mock transfected pcDNA3 cells, which required a higher dose (75 μM). Both pcDNA3 and Tyr+ DB-1 cells demonstrated similar increases in phosphorylation of p53 at other serine sites, but in the Tyr+ cells, DNApk expression was found to be reduced compared to control cells, indicating a shift towards an ATM-mediated response. The DB-1 control cells were resistant to DTIC, but were sensitized to apoptosis with high dose Qct, while Tyr+ cells were sensitized to DTIC with low or high dose Qct. Qct also sensitized SK Mel 5 (p53 wildtype) and 28 (p53 mutant) cells to DTIC. However, when SK Mel 5 cells were transiently transfected with tyrosinase and treated with Qct plus DTIC, SK Mel 5 cells demonstrated a more than additive induction of apoptosis. Therefore, this study demonstrates that tyrosinase overexpression promotes an ATM-dependent p53 phosphorylation by Qct treatment and sensitizes melanoma cells to dacarbazine. In conclusion, these results suggest that Qct or Qct analogues may significantly improve DTIC response rates in tumors that express tyrosinase.

scholarly journals Taxane-Induced Upper Gastrointestinal Bleeding

2021 ◽  
pp. 1373-1379
Author(s):  
Yao Liu ◽  
Brent Hiramoto ◽  
Janet Kwok ◽  
Ahmad Ibrahim ◽  
Sergei Tatishchev ◽  
...  
Keyword(s):  
Gastrointestinal Bleeding ◽  
Chemotherapy Regimen ◽  
Upper Gastrointestinal Bleeding ◽  
Chemotherapeutic Agent ◽  
Subsequent Removal ◽  
Neutropenic Enterocolitis ◽  
Chemotherapy Agent ◽  
Upper Gastrointestinal Bleed ◽  
Gastrointestinal Side Effects ◽  
Upper Gastrointestinal

Docetaxel is a taxane, which is a class of chemotherapy agent used in the treatment of multiple malignancies. It is known to have gastrointestinal side effects which can range from mild symptoms such as nausea and diarrhea to more severe complications such as neutropenic enterocolitis. In the current literature, taxanes have not been described to cause upper gastrointestinal bleeding and melena. Here, we present a case of a 54-year-old woman with breast cancer who developed dizziness, fatigue, and melena after receiving chemotherapy. Esophagogastroduodenoscopy revealed diffuse gastric erosions as well as ulceration and linear superficial lesions in the duodenum; biopsies from these sites showed taxane-induced toxicity. Her bleeding resolved with medical therapy and subsequent removal of docetaxel from her chemotherapy regimen. This case identifies upper gastrointestinal bleeding as a previously undescribed side effect of docetaxel therapy. Recent docetaxel use should be included in the differential diagnosis for upper gastrointestinal bleed, and diagnosis should lead to consideration of cessation of docetaxel or substitution with another chemotherapeutic agent.

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