An effective strategy for development of docetaxel encapsulated gold nanoformulations for treatment of prostate cancer.

Published on Feb 2, 2021in Scientific Reports3.998
· DOI :10.1038/S41598-020-80529-1
S. Thambiraj6
Estimated H-index: 6
(University of Madras),
R. Vijayalakshmi1
Estimated H-index: 1
,
D. Ravi Shankaran9
Estimated H-index: 9
(University of Madras)
Sources
Abstract
Nanoformulation based drug delivery is one of the most important research areas in the field of nanomedicine, which provides promising alternatives to the limitations of conventional chemotherapy. Nano drug delivery enables improved pharmacokinetic profile, bioavailability and therapeutic efficiency compared to the regular chemotherapeutic drugs. Herein, we have established a simple method for the synthesis of docetaxel (Dtx) encapsulated poly (ethylene glycol) (PEG) functionalized gold nanoparticles (AuNPs) for targeted drug delivery to prostate cancer. AuNPs were synthesized by the citrate ion reduction method followed by functionalization with thiol-PEG-amine (SH-PEG-NH2). SH-PEG-NH2 functionalized AuNPs were conjugated with the targeting vehicle, folic acid (FA). The anticancer drug, Dtx was encapsulated within AuNPs by the non-covalent linkage method. The physicochemical characteristics of the synthesized nanoformulations were extensively characterized by various spectral and microscopic studies. HR-TEM indicates the average size of the AuNPs is 16 nm and the nanoformulations is 18 nm. The encapsulation efficiency of the Dtx is ~ 96% which is confirmed by the elemental mapping analysis. The in vitro drug release profile of Dtx and AuNPs nanoformulations were studied by the dialysis membrane method. The anticancer activity of docetaxel encapsulated AuNPs were evaluated with prostate cancer cell lines (PC3). The drug encapsulated nanoformulations reduced the cell viability to about 40% (40 µM concentration at 24, 48 and 72 h of treatment). The optical microscopy observation reveals that the damage of prostate cancer cells after exposure to Dtx encapsulated AuNPs. The good cytotoxic activity of the present nanoformulation against prostate cancer cell lines enables its application for targeted drug delivery to prostate cancer.
References77
Newest
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Since the introduction of PSA testing, significantly more men have been diagnosed and treated for prostate cancer. Localized prostate cancer typically is treated with prostatectomy, however there is still a high risk of recurrence after surgery, and adjuvant radiation has been shown to mitigate disease progression. X-ray therapy is frequently used as an adjuvant to treat prostate cancer, but is an imperfect tool. In this report we describe the development of a targeted-radiosensitizing nanoparti...
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Although docetaxel is currently broadly used in prostate cancer treatment, poor water solubility and systemic toxicity limit the dose and duration of therapy. In this context, although different nanoplatforms have been proposed to overcome these issues, selective therapy needs developing methodologies to target malignant cells and minimizing the impact on healthy tissue. We here present a novel drug delivery system obtained by covalent conjugation of docetaxel and an anti-prostate specific membr...
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#2S. ShruthiH-Index: 1
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Abstract The effective use of the gold nanoparticle (AuNPs) conjugated drugs for targeted drug delivery applications is one of the most promising research areas in the field of cancer. Herein, we aimed to establish a nano drug conjugated with docetaxel as a possible therapy option. Gold nanoparticles were synthesized by chemical reduction method. This is followed by the conjugation with an anticancer drug, docetaxel (Dtx) by a non-covalent method and folic acid (FA) was conjugated by a covalent ...
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Cancer is the second leading causes of death worldwide and it is one of the fatal diseases that kill millions of people every year. It is characterized by uncontrolled proliferation of cells and loss of apoptosis that generates an abnormal mass of cells or tumors. Prostate cancer (PCa) is one of the most common cancers in men and the risk is higher over the age of 55-65. Currently, PCa is the second most common cancer, which causes death in men has a high prevalence with relatively lower cancer ...
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Development of folate (FA)-functionalized gold nanoparticles (AuNPs) has greatly increased in recent years due to their potential in cancer treatment. As surface functionalization of polymer-free AuNPs with thiol groups could result in agglomeration and precipitation, AuNPs should be stabilized with an efficient polymer. In this study, citric acid-PEG branched polymer (CPEG) acted as a reducing as well as stabilizing agent in the synthesis of AuNPs. The thiol group of thioglycolic acid (TGA) att...
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: Advances in nanotechnology have led to the design of multifunctional nanoparticles capable of cellular imaging, targeted drug delivery, and diagnostics for early cancer detection. We synthesized poly(lactic-co-glycolic acid) nanoparticles encapsulating a model radiosensitizing drug docetaxel accomplishing localized in situ delivery of the sensitizer to the tumor site. The synthesized nanoparticles have been characterized for their physicochemical properties. The in vitro cytotoxicity of drug-l...
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Abstract Gold nanoparticles (AuNPs) have been receiving great attention over the years due to their unique optical, electrical and biological properties. The functionalization of AuNPs is an important research interest owing to its potential application in various areas including biomedical, defense, food and environmental. Herein, we demonstrate a simple and effective method for the synthesis of functionalized AuNPs. Gold nanoparticles were synthesized by chemical reduction method using trisodi...
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#2Soundararajan Hema (University of Madras)H-Index: 3
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BACKGROUND: Carcinoma of the prostate gland (PCa) is one of the most commonly diagnosed cancer diseases among men around the world. PCa has become the major considerable health and epidemic problem which causes death in men with a high prevalence and relatively lower mortality risk. The inability of conventional diagnosis tools to detect cancer at an early and potentially curable stage further hinders effective treatment options and spur demand for improved technologies. Nanoparticles are emergi...
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: Personalized and precise nanomedicines are highly demanded for today's medical needs. Liposomes are ideal candidates for the construction of multifunctional drug delivery systems. In this study, a liposome was used to improve the clinical issues of docetaxel (Doc), a potent antimitotic chemotherapy for prostate cancer (PC). RLT, a low-density lipoprotein receptor (LDLR)-binding peptide, and PEG were conjugated to the liposomes, and gold nanorods (GNRs) were also incorporated into the liposomes...
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