scholarly journals PEGylated Mesoporous Silica Nanoparticles (MCM-41): A Promising Carrier for the Targeted Delivery of Fenbendazole into Prostrate Cancer Cells

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1605
Author(s):  
Maedeh Koohi Moftakhari Esfahani ◽  
Seyed Ebrahim Alavi ◽  
Peter J. Cabot ◽  
Nazrul Islam ◽  
Emad L. Izake
Keyword(s):  
Prostate Cancer ◽  
Targeted Delivery ◽  
Water Solubility ◽  
Mesoporous Silica Nanoparticles ◽  
Drug Carrier ◽  
Spherical Shape ◽  
Prostrate Cancer ◽  
Treat Prostate Cancer ◽  
Cytotoxicity Effects

Low water solubility and thus low bioavailability limit the clinical application of fenbendazole (FBZ) as a potential anticancer drug. Solubilizing agents, such as Mobil Composition of Matter Number 41 (MCM) as a drug carrier, can improve the water solubility of drugs. In this study, PEGylated MCM (PEG-MCM) nanoparticles (NPs) were synthesized and loaded with FBZ (PEG-MCM-FBZ) to improve its solubility and, as a result, its cytotoxicity effect against human prostate cancer PC-3 cells. The loading efficiency of FBZ onto PEG-MCM NPs was 17.2%. The size and zeta potential of PEG-MCM-FBZ NPs were 366.3 ± 6.9 nm and 24.7 ± 0.4 mV, respectively. They had a spherical shape and released the drug in a controlled manner at pH 1.2 and pH 6.2. PEG-MCM-FBZ were found to inhibit the migration of PC-3 cells, increase the cytotoxicity effects of FBZ against PC-3 cells by 3.8-fold, and were more potent by 1.4-fold, when compared to the non-PEGylated NPs. In addition, PEG-MCM-FBZ promoted the production of reactive oxygen species by 1.3- and 1.2-fold, respectively, when compared to FBZ and MCM-FBZ. Overall, the results demonstrate that PEG-MCM-FBZ NPs enhanced FBZ delivery to PC-3 cells; therefore, they have the potential to treat prostate cancer after a comprehensive in vivo study.

scholarly journals Exosomes Derived from Nanocomplex-Loaded Macrophages for Targeted Delivery of Docetaxel and siPLK1 against Castrate-Resistance Prostate Cancer

2020 ◽  
Author(s):  
Jing Tian ◽  
Zongguang Tai ◽  
Wei Zhang ◽  
Xiaoyu Wang ◽  
Zhongjian Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Targeted Delivery ◽  
Drug Carrier ◽  
Drug Loading ◽  
Clinical Applications ◽  
Raw264.7 Macrophages ◽  
New Strategy ◽  
Targeting Ability ◽  
Reduced Toxicity

Abstract Background. As a class of naturally occurring nanoparticles with low immunogenicity and high biocompatibility, exosomes have become a promising drug carrier for cancer therapy. However, their clinical applications remain a challenge due to their unsuitable donors, low scalability, as well as insufficient targeting ability. Here, we describe and validate a new strategy for drug loading into exosomes. We developed a folate-conjugated exosome (Co-Exo-FA) derived from nanocomplex-loaded Raw264.7 macrophages. This Co-Exo-FA containing docetaxel (DTX) and PLK1 siRNA (siPLK1) could be used for targeted therapy of castrate-resistance prostate cancer (CRPC).Results. Our results showed that Co-Exo-FA exhibited high stability, enhanced cancer targeting ability, and led to the suppression of tumor growth with reduced toxicity in vivo. Moreover, the delivery of siPLK1 and DTX using an exosome system effectively silenced the PLK1 gene and exhibited improved anticancer effects.Conclusion. Our results indicated that we managed to overcome major barriers to the efficient utility of exosomes and demonstrated the synergistic efficacy of siPLK1 and DTX in the treatment of CRPC, highlighting their potential value in therapeutic clinical applications.

scholarly journals Oligo(Lactic Acid)8-Docetaxel Prodrug-Loaded PEG-b-PLA Micelles for Prostate Cancer

Nanomaterials ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 2745
Author(s):  
Lauren Repp ◽  
Christopher J. Unterberger ◽  
Zhengqing Ye ◽  
John B. Feltenberger ◽  
Steven M. Swanson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lactic Acid ◽  
Water Solubility ◽  
Polymeric Micelles ◽  
Drug Carrier ◽  
Aqueous Media ◽  
Water Soluble ◽  
Poly Lactic Acid ◽  
Chemotherapy Drugs

Docetaxel (DTX) is among the most frequently prescribed chemotherapy drugs and has recently been shown to extend survival in advanced prostate cancer patients. However, the poor water solubility of DTX prevents full exploitation of this potent anticancer drug. The current marketed formulation, Taxotere®, contains a toxic co-solvent that induces adverse reactions following intravenous injection. Nano-sized polymeric micelles have been proposed to create safer, water-soluble carriers for DTX, but many have failed to reach the clinic due to poor carrier stability in vivo. In this study, we aimed to improve micelle stability by synthesizing an ester prodrug of DTX, oligo(lactic acid)8-docetaxel (o(LA)8-DTX), for augmented compatibility with the core of poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA) micelles. Due to the enhancement of drug-carrier compatibility, we were able to load 50% (w/w) prodrug within the micelle, solubilize 20 mg/mL o(LA)8-DTX (~12 mg/mL DTX-equivalent) in aqueous media, and delay payload release. While the micelle core prohibited premature degradation, o(LA)8-DTX was rapidly converted to parent drug DTX through intramolecular backbiting (t1/2 = 6.3 h) or esterase-mediated degradation (t1/2 = 2.5 h) following release. Most importantly, o(LA)8-DTX micelles proved to be as efficacious but less toxic than Taxotere® in a preclinical mouse model of prostate cancer.

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.

scholarly journals NANOEMULSIONS FOR PROSTRATE CANCER THERAPY: AN OVERVIEW

2017 ◽  
Vol 10 (5) ◽  
pp. 37
Author(s):  
Manikandan P ◽  
Sundara Ganapathy R
Keyword(s):  
Prostate Cancer ◽  
Oral Delivery ◽  
Water Solubility ◽  
Oral Absorption ◽  
Solid Dispersions ◽  
Dose Proportionality ◽  
Permeation Enhancers ◽  
Lipophilic Drugs ◽  
Prostrate Cancer ◽  
Gastric Fluids

The objective of this review is to focus the inferences of low/poor bioavailability and lack of dose proportionality for the oral delivery of drugs in prostatecancer therapy. To overcome such problems, various formulation strategies has been reported including various methods for the use of surfactants,cyclodextrins, solid dispersions, micronization, permeation enhancers, and lipids. Flutamide is an antiandrogen drug and used for the therapy of prostate cancer. The flutamide drug is having limited clinical application due to its poor water solubility and needs enhancement of its dissolution rate in simulated gastric fluids. The lipid-based formulations such as nanoemulsion have been shown to improve the solubility and oral absorption of lipophilic drugs. To conclude, this article emphasizes the various approaches of nanoemulsion based formulation for prostate cancer therapy.Keywords: Nanoemulsion, Prostate cancer, Flutamide, Antiandrogen drug, Lipophilic drugs.

Intercellular Crosstalk of Mesenchymal Stem Cells with Prostate Cancer Cells via Microvesicles Loaded with Magnetic Nanocubes for Targeted Magnetic Hyperthermia

2019 ◽  
Vol 15 (12) ◽  
pp. 2291-2304
Author(s):  
Liqun Huang ◽  
Mengwei Chen ◽  
Chang Xu ◽  
Qishuai Feng ◽  
Jiaojiao Wu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Magnetic Hyperthermia ◽  
Migration Ability ◽  
Hyperthermia Therapy

The targeted delivery of nanomedicines into solid tumors remains challenging in cancer treatment. Stem cells with tumortropic migration ability are promising as biocarriers to transport nanomedicines. The transportation of nanomedicines into cancer cells is the key step for tumor targeted delivery via stem cells. In this study, we designed a magnetic nanocube (scMNP) loaded in mesenchymal stem cells for magnetic hyperthermia of prostate cancer, and the delivery and transportation pathways into the cancer cells were fully investigated. The MSCs acted as the carrier of the loaded scMNPs along with the upregulation of CXCR4 for the migration to cancer cells. The therapeutic effect was mainly due to scMNPs via magnetic hyperthermia. Stem cell-derived microvesicles containing scMNPs played an essential role in the crosstalk between stem cells and cancer cells for targeted delivery. Both in vitro and in vivo studies demonstrated that the system showed satisfactory therapeutic efficiency under magnetic hyperthermia therapy. Our investigation presents a comprehensive study of magnetic nanoparticles in combination with MSCs and their extracellular microvesicles and is promising as an effective strategy for magnetic hyperthermia therapy of prostate cancer.

Preparation and Characterization of Heparin-Retinoic Acid-Folic Acid Conjugates for Targeted Cancer Therapy

2010 ◽  
Vol 93-94 ◽  
pp. 324-327 ◽  
Author(s):  
Il Kyu Park ◽  
Yu Jin Kim ◽  
Kang Moo Huh ◽  
Yong Kyu Lee
Keyword(s):  
Folic Acid ◽  
Water Solubility ◽  
Drug Carrier ◽  
Ultra Violet ◽  
Proton Nuclear Magnetic Resonance ◽  
Coagulation Cascade ◽  
Cancer Drug ◽  
Great Promise ◽  
Target Cells

To make significant progress in the fight against cancer, treatment should target cells more specifically, produce fewer side effects, be easy to administer and deter tumor viability on multiple levels. We have attained dramatic in vivo tumor shrinkage and tumor vasculature disruption using a ternary biomolecular nanoparticle comprised of polymeric carrier polysaccharide heparin, anticancer drug retinoid and targeting ligand folic acid. The conjugation of retinoid and folic acid to heparin enhanced the water solubility of the drug, enabled selective targeting, and enhanced the role of heparin as anti-cancer drug carrier by eluding the coagulation cascade. This approach for targeting tumor holds great promise for treatment of various types of cancer. The folic acid linked heparin-retinoid conjugates (HFR) reactions was conjugated with ester and amide bonding which was confirmed by fourier transform infrared (FT-IR) and proton nuclear magnetic resonance (1H-NMR). The ratio of HFR conjugates was measured with Ultra-Violet spectrometry (UV-spectrometry). The particle size of HFR nanoparticles was measured by dynamic light scattering (DLS), and transmission electron microscopy (TEM). HFR conjugates were spherical and showed a diameter range of 200-300 nm in size. The nanoparticles maintained their stability in serum condition for 48hrs and have the high potential for applications in biomedical field.

Effect of PEDF on the in vivo antitumor activities of low-dose chemotherapy in CRPC.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 173-173
Author(s):  
Thomas Nelius ◽  
Everardo Cobos ◽  
Jennifer Hirsch ◽  
Stephanie Filleur
Keyword(s):  
Prostate Cancer ◽  
Low Dose ◽  
Pigment Epithelium ◽  
Growth Curves ◽  
Great Promise ◽  
Tumor Bearing ◽  
Cytotoxicity Effects ◽  
Low Dose Chemotherapy

173 Background: The development of metronomic/low dose administration of conventional chemotherapeutic drugs has shown great promise in the treatment of castration-refractory prostate cancer (CPRC). Pigment Epithelium-Derived Factor (PEDF) is a natural angio-inhibitor which is down-regulated in prostate cancer. We have previously demonstrated that the over-expression of PEDF in human CRPC PC3 cells decreased tumor growth in vivo. In the present study, we further validated PEDF anti-tumor properties in the highly metastatic CRPC LNCaP-derivative CL1 cells. We also hypothesized that PEDF may enhance the cytotoxicity effects of low dose docetaxel (DTX) and cyclophosphamide (CTX) chemotherapies in vivo. Methods: PC3 and CL1 cell lines were genetically modified to stably express the fluorescent DsRed Express protein with PEDF. Resulting cells were characterized in vitro for PEDF expression by western blot and, for proliferation by growth curves and clone formation in matrigel. PEDF anti-tumor effects were assessed on established s.c. xenografts in mice treated with DTX (5mg/kg ip every 4 days, 1mg/kg ip daily for 10 days, 0.5mg/kg every other day), CTX (10-20mg/kg in the drinking water) or placebo. Survival studies were performed by injecting CL1-PEDF or -control cells into the left lobe of the dorsal prostate of anesthetized mice. Results: We showed that PEDF expression inhibits the proliferation and induces the differentiation of CPRC cells in vitro, and decreases by 85% and 70% the development of s.c. PC3 and CL1 tumors, respectively. In the survival study, PEDF expression prolongs significantly (P=0.01; 95% confidence interval) the median survival of CL1 tumor-bearing mice (53±0.001 days versus 57±1). Furthermore, we demonstrated that PEDF enhances the cytotoxicity effects of low dose chemotherapy on established s.c. tumors (best Doc dose: 1mg/kg for PC3 and 5mg/kg for CL1; best CTX dose: 10mg/kg for PC3 and CL1) and prolongs significantly the survival of tumor-bearing mice undergoing low dose chemotherapy. Conclusions: These data reinforce the significance of PEDF as a potent target for the treatment of CRPC. It also emphasizes PEDF as a promising new agent to enhance the anti-tumor efficacy of low dose chemotherapies.

scholarly journals Small Molecule-Based Prodrug Targeting Prostate Specific Membrane Antigen for the Treatment of Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 417
Author(s):  
Xinning Wang ◽  
Aditi Shirke ◽  
Ethan Walker ◽  
Rongcan Sun ◽  
Gopolakrishnan Ramamurthy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Small Molecule ◽  
Targeted Delivery ◽  
Treatment Options ◽  
Maximum Tolerated Dose ◽  
In Vivo Studies ◽  
Castration Resistant Prostate Cancer ◽  
Drug Conjugates

Metastatic castration-resistant prostate cancer poses a serious clinical problem with poor outcomes and remains a deadly disease. New targeted treatment options are urgently needed. PSMA is highly expressed in prostate cancer and has been an attractive biomarker for the treatment of prostate cancer. In this study, we explored the feasibility of targeted delivery of an antimitotic drug, monomethyl auristatin E (MMAE), to tumor tissue using a small-molecule based PSMA lig-and. With the aid of Cy5.5, we found that a cleavable linker is vital for the antitumor activity of the ligand–drug conjugate and have developed a new PSMA-targeting prodrug, PSMA-1-VcMMAE. In in vitro studies, PSMA-1-VcMMAE was 48-fold more potent in killing PSMA-positive PC3pip cells than killing PSMA-negative PC3flu cells. In in vivo studies, PSMA-1-VcMMAE significantly inhibited tumor growth leading to prolonged animal survival in different animal models, including metastatic prostate cancer models. Compared to anti-PSMA antibody-MMAE conjugate (PSMA-ADC) and MMAE, PSMA-1-VcMMAE had over a 10-fold improved maximum tolerated dose, resulting in improved therapeutic index. The small molecule–drug conjugates reported here can be easily synthesized and are more cost efficient than anti-body–drug conjugates. The therapeutic profile of the PSMA-1-VcMMAE encourages further clin-ical development for the treatment of advanced prostate cancer.

Hybrid biomaterial based on porous silica nanoparticles and Pluronic F-127 for sustained release of sildenafil: in vivo study on prostate cancer

RSC Advances ◽  
2015 ◽  
Vol 5 (99) ◽  
pp. 81348-81355 ◽  
Author(s):  
C. P. Silveira ◽  
L. M. Apolinário ◽  
W. J. Fávaro ◽  
A. J. Paula ◽  
N. Durán
Keyword(s):  
Prostate Cancer ◽  
Mesoporous Silica ◽  
Sustained Release ◽  
Silica Nanoparticles ◽  
High Efficiency ◽  
Mesoporous Silica Nanoparticles ◽  
Porous Silica ◽  
In Vivo Study ◽  
Hydrogel System

We describe here a drug depot hydrogel system comprising sildenafil (Viagra®) incorporated in mesoporous silica nanoparticles (60 nm) and conjugated with a thermosensitive poloxamer, which presents a high efficiency against prostate cancer.

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