scholarly journals Folated Synperonic-Cholesteryl Hemisuccinate Polymeric Micelles for the Targeted Delivery of Docetaxel in Melanoma

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Jaleh Varshosaz ◽  
Somayeh Taymouri ◽  
Farshid Hassanzadeh ◽  
Shaghayegh Haghjooy Javanmard ◽  
Mahboobeh Rostami
Keyword(s):  
Cellular Uptake ◽  
Targeted Delivery ◽  
Polymeric Micelles ◽  
Fluorescent Microscopy ◽  
Melanoma Tumor ◽  
Anticancer Efficacy ◽  
Solvent Type ◽  
Dialysis Method ◽  
Cholesteryl Hemisuccinate

The objective of this study was the synthesis of folic acid- (FA-) targeted polymeric micelles of Synperonic PE/F 127-cholesteryl hemisuccinate (PF127-Chol) for specific delivery of docetaxel (DTX). Targeted or nontargeted micelles loaded with DTX were prepared via dialysis method. The effects of processing variables on the physicochemical properties of targeted micelles were evaluated using a full factorial design. After the optimization of the polymer/drug ratio, the organic solvent type used for the preparation of the micelles, and the temperature of dialyzing medium, thein vitrocytotoxicity and cellular uptake of the optimized micelles were studied on B16F10 melanoma cells by flow cytometry and fluorescent microscopy. The anticancer efficacy of DTX-loaded FA-PF127-Chol was evaluated in mice bearing melanoma tumor. Optimized targeted micelles had the particle size of 171.3 nm, zeta potential of −7.8 mV, PDI of 0.325, and a high encapsulation efficiency that released the drug within 144 h. The MTT assay indicated that targeted micelles carrying DTX were significantly more cytotoxic, had higher cellular uptake, and reduced the tumor volume significantly more than the nontargeted micelles and the free drug. FA-PF127-Chol could be, therefore, a promising biomaterial for tumors overexpressing folate receptors.

Recent Advances in Curcumin Nanocarriers for the Treatment of Different Types of Cancer with Special Emphasis on In Vitro Cytotoxicity and Cellular Uptake Studies

2020 ◽  
Vol 10 (5) ◽  
pp. 577-590
Author(s):  
Jai B. Sharma ◽  
Shailendra Bhatt ◽  
Asmita Sharma ◽  
Manish Kumar
Keyword(s):  
Cancer Cells ◽  
Cellular Uptake ◽  
Anticancer Agents ◽  
Targeted Delivery ◽  
In Vitro Cytotoxicity ◽  
Curcumin Nanoparticles ◽  
Cytotoxicity Studies ◽  
Delivery Technique ◽  
Different Types

Background: The potential use of nanocarriers is being explored rapidly for the targeted delivery of anticancer agents. Curcumin is a natural polyphenolic compound obtained from rhizomes of turmeric, belongs to family Zingiberaceae. It possesses chemopreventive and chemotherapeutic activity with low toxicity in almost all types of cancer. The low solubility and bioavailability of curcumin make it unable to use for the clinical purpose. The necessity of an effective strategy to overcome the limitations of curcumin is responsible for the development of its nanocarriers. Objective: This study is aimed to review the role of curcumin nanocarriers for the treatment of cancer with special emphasis on cellular uptake and in vitro cytotoxicity studies. In addition to this, the effect of various ligand conjugated curcumin nanoparticles on different types of cancer was also studied. Methods: A systematic review was conducted by extensively surfing the PubMed, science direct and other portals to get the latest update on recent development in nanocarriers of curcumin. Results: The current data from recent studies showed that nanocarriers of curcumin resulted in the targeted delivery, higher efficacy, enhanced bioavailability and lower toxicity. The curcumin nanoparticles showed significant inhibitory effects on cancer cells as compared to free curcumin. Conclusion: It can be concluded that bioavailability of curcumin and its cytotoxic effect to cancer cells can be enhanced by the development of curcumin based nanocarriers and it was found to be a potential drug delivery technique for the treatment of cancer.

HYALURONIC ACID-DOCETAXEL CONJUGATE LOADED NANOLIPOSOMES FOR TARGETING TUMOR CELLS

2020 ◽  
pp. 88-99
Author(s):  
MULUNEH FROMSA SEIFU ◽  
LILA KANTA NATH ◽  
DEBASHIS DUTTA
Keyword(s):  
Hyaluronic Acid ◽  
Glial Cells ◽  
Cellular Uptake ◽  
Drug Loading ◽  
Microscopic Investigation ◽  
In Vitro Cytotoxicity ◽  
Scanning Calorimetry ◽  
Anticancer Efficacy ◽  
Apoptotic Effect

Objective: Docetaxel (DTX), a potent anticancer drug, is suffering from non-specificity and drug resistance as major limitations. In this investigation, we developed Hyaluronic acid (HA)-Docetaxel conjugate (HA-DTX) loaded nanoliposomes to target cancer cells via passive and active targeting approaches. Methods: HA-DTX was synthesized and characterized by UV-Visible spectrophotometry, FT-IR spectroscopy, 1H NMR spectroscopy, Differential scanning calorimetry and X-ray diffraction and then loaded into nanoliposomes (L-NLs) by thin-film hydration method. L-NLs were characterized physicochemically and evaluated for anticancer efficacy by in vitro cytotoxicity study in glioma cells (C6 glial cells); cellular uptake and apoptotic effect were investigated by fluorescence microscopy. Results: HA-DTX was successfully synthesized; L-NLs had an average size of 123.0±16.53 nm, polydispersity index of 0.246±0.01 and zeta potential of 44.4±6.79 mV. Also, L-NLs exhibited 90.54%±4.22 of drug loading efficiency and 2.68%±0.12 of drug loading, releasing about 57.72%±1.17 at pH 5.2 and only 14.14%±1.32 at pH 7.4 after 48 h. No significant change instability was observed after storage at 5 °C±3 °C as well as at 25 °C±2 °C/60% RH±5% RH for 6 mo. The cytotoxicity effect of L-NLs was higher by 10% that of marketed formulation at 10 µg/ml docetaxel concentration. Fluorescence microscopic investigation showed that more cellular uptake and apoptotic effect were observed in L-NLs treated C6 glial cells than in those treated with the marketed formulation. Conclusion: HA-DTX loaded nanoliposomes enabled docetaxel to target C6 glial cells with better efficacy and might be effective to treat glioma.

In Vitro Cytotoxicity and Cellular Uptake of Tamoxifen Citrate-Loaded Polymeric Micelles

2020 ◽  
Vol 21 (8) ◽  
Author(s):  
Mohamed Nasr ◽  
Fahima Hashem ◽  
Raghda Abdelmoniem ◽  
Norhan Tantawy ◽  
Mohamed Teiama
Keyword(s):  
Cellular Uptake ◽  
Polymeric Micelles ◽  
In Vitro Cytotoxicity ◽  
Tamoxifen Citrate

Co-Polymer Functionalised Gold Nanoparticles Show Efficient Mitochondrial Targeted Drug Delivery in Cervical Carcinoma Cells

2020 ◽  
Vol 16 (6) ◽  
pp. 853-866
Author(s):  
Olakunle Oladimeji ◽  
Jude Akinyelu ◽  
Moganavelli Singh
Keyword(s):  
Cancer Cells ◽  
Cervical Carcinoma ◽  
Targeted Delivery ◽  
Fluorescent Microscopy ◽  
Epigallocatechin Gallate ◽  
Laminin Receptor ◽  
Subcellular Targeting ◽  
Therapeutic Principles ◽  
Novel Target

The mitochondria have recently become a novel target in the treatment of cancer. Targeted delivery by nanoparticles (NPs) has shown potential in enhancing existing therapeutic principles. With toxicity remaining a recurring issue, the green synthesis of inorganic NPs and modification with polymers may help to improve stability and biocompatibility. We synthesized epigallocatechin gallate (EGCG)-capped gold NPs (AuNPs), and functionalized with poly-D-lysine grafted polyethylene glycol (PDL-g-PEG), and the mitochondrial targeting triphenylphosphonium cation, and thereafter assessed their mitochondrial delivery capacity of paclitaxel in cancer cells in vitro. This PDL-g-PEG coated EGCG-AuNPs were further assessed for their laminin receptor avidity and mitochondrial localisation potential, upon functionalisation with the delocalised cation, triphenylphosphine. The laminin receptor dependent uptake and mitochondrial localisation of targeted T-Au(PDL-g-PEG) NPs were confirmed by ICP-OES and fluorescent microscopy. Their delivery of paclitaxel to the mitochondria of cancer cells elicited significant cytotoxicity especially in the human cervical carcinoma (HeLa) cell line, compared to the untargeted T-Au(PDL-g-PEG) and free drugs. Mechanistic studies implicated caspase dependent apoptosis as the mechanism of cell death. Our findings demonstrate the capacity of T-Au-[PDL-PEG] NPs to preferentially localize in the tumour mitochondria, and confirms the potential impact of subcellular targeting, especially to the mitochondria in cancer cells for an improvement in the therapeutic indices of these drugs.

scholarly journals The anticancer efficacy of paclitaxel liposomes modified with low-toxicity hydrophobic cell-penetrating peptides in breast cancer: an in vitro and in vivo evaluation

RSC Advances ◽  
2018 ◽  
Vol 8 (43) ◽  
pp. 24084-24093 ◽  
Author(s):  
Qi Zhang ◽  
Jing Wang ◽  
Hao Zhang ◽  
Dan Liu ◽  
Linlin Ming ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Delivery ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating Peptide ◽  
In Vivo Evaluation ◽  
Anticancer Efficacy ◽  
Cell Penetrating ◽  
Low Toxicity

Hydrophobic cell penetrating peptide PFVYLI-modified liposomes have been developed for the targeted delivery of PTX into tumors.

scholarly journals Synthesis and Characterization of pH-Sensitive Inulin Conjugate of Isoniazid for Monocyte-Targeted Delivery

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 555 ◽  
Author(s):  
Franklin Afinjuomo ◽  
Thomas G. Barclay ◽  
Ankit Parikh ◽  
Rosa Chung ◽  
Yunmei Song ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Targeted Delivery ◽  
Ph Sensitive ◽  
Proton Nuclear Magnetic Resonance ◽  
Antitubercular Drugs ◽  
Intracellular Targeting ◽  
Intracellular Drug Delivery ◽  
Uptake Studies ◽  
Endocytic Compartments

The use of particles for monocyte-mediated delivery could be a more efficient strategy and approach to achieve intracellular targeting and delivery of antitubercular drugs to host macrophages. In this study, the potential of inulin microparticles to serve as a drug vehicle in the treatment of chronic tuberculosis using a monocytes-mediated drug targeting approach was evaluated. Isoniazid (INH) was conjugated to inulin via hydrazone linkage in order to obtain a pH-sensitive inulin-INH conjugate. The conjugate was then characterized using proton nuclear magnetic resonance (1HNMR), Fourier transform infrared spectroscopy (FTIR) as well as in vitro, cellular uptake and intracellular Mycobacterium tuberculosis (Mtb) antibacterial efficacy. The acid-labile hydrazone linkage conferred pH sensitivity to the inulin-INH conjugate with ~95, 77 and 65% of the drug released after 5 h at pH 4.5, 5.2, and 6.0 respectively. Cellular uptake studies confirm that RAW 264.7 monocytic cells efficiently internalized the inulin conjugates into endocytic compartments through endocytosis. The intracellular efficacy studies demonstrate that the inulin conjugates possess a dose-dependent targeting effect against Mtb-infected monocytes. This was through efficient internalization and cleavage of the hydrazone bond by the acidic environment of the lysosome, which subsequently released the isoniazid intracellularly to the Mtb reservoir. These results clearly suggest that inulin conjugates can serve as a pH-sensitive intracellular drug delivery system for TB treatment.

Quinolin-8-yloxy-substituted zinc(II) phthalocyanines for enhanced in vitro photodynamic therapy

2018 ◽  
Vol 22 (09n10) ◽  
pp. 807-813 ◽  
Author(s):  
Juanjuan Chen ◽  
Yuting Fang ◽  
Hong Liu ◽  
Naisheng Chen ◽  
Shengping Chen ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Singlet Oxygen ◽  
Clinical Application ◽  
Cellular Uptake ◽  
Culture Medium ◽  
Anticancer Agent ◽  
Quantum Yields ◽  
Anticancer Efficacy ◽  
Self Aggregation

Photodynamic therapy (PDT) is an innovative and promising modality to treat various tumors. In this study, two novel zinc(II) phthalocyanines substituted with quinolin-8-yloxy groups at the [Formula: see text]-position, namely mono(quinolin-8-yloxy) zinc(II) phthalocyanine (ZnPc-Q1) and tetra(quinolin-8-yloxy) zinc(II) phthalocyanine (ZnPc-Q4), have been synthesized and fully characterized. With quinolin-8-yloxy, these two phthalocyanines exhibit less self-aggregation in DMF and culture medium, high singlet oxygen quantum yields, mitochondria localization and high photodynamic activities (IC[Formula: see text] values as low as 2 nM). Compared to ZnPc-Q4, ZnPc-Q1 exhibits higher cellular uptake and lower IC[Formula: see text] values. Benefitting from its higher anticancer efficacy and lack of isomers, ZnPc-Q1 is a highly promising anticancer agent in clinical application.

scholarly journals A multistage assembly/disassembly strategy for tumor-targeted CO delivery

2020 ◽  
Vol 6 (20) ◽  
pp. eaba1362 ◽  
Author(s):  
Jin Meng ◽  
Zhaokui Jin ◽  
Penghe Zhao ◽  
Bin Zhao ◽  
Mingjian Fan ◽  
...  
Keyword(s):  
Controlled Release ◽  
Targeted Delivery ◽  
Tumor Tissue ◽  
Silica Nanoparticle ◽  
Tissue Cell ◽  
Anticancer Efficacy ◽  
Electrostatic Assembly ◽  
Gas Molecule

CO gas molecule not only could selectively kill cancer cells but also exhibits limited anticancer efficacy because of the lack of active tumor-targeted accumulation capability. In this work, a multistage assembly/disassembly strategy is developed to construct a new intelligent nanomedicine by encapsulating a mitochondria-targeted and intramitochondrial microenvironment–responsive prodrug (FeCO-TPP) within mesoporous silica nanoparticle that is further coated with hyaluronic acid by step-by-step electrostatic assembly, realizing tumor tissue–cell–mitochondria–targeted multistage delivery and controlled release of CO in a step-by-step disassembly way. Multistage targeted delivery and controlled release of CO involve (i) the passive tumor tissue–targeted nanomedicine delivery, (ii) the active tumor cell–targeted nanomedicine delivery, (iii) the acid-responsive prodrug release, (iv) the mitochondria-targeted prodrug delivery, and (v) the ROS-responsive CO release. The developed nanomedicine has effectively augmented the efficacy and safety of CO therapy of cancer both in vitro and in vivo. The proposed multistage assembly/disassembly strategy opens a new window for targeted CO therapy.

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.

scholarly journals A novel method for producing functionalized vesicles that efficiently deliver oligonucleotides in vitro and in vivo in mice

2021 ◽  
Author(s):  
Pragati Jain ◽  
Arthur G. Roberts
Keyword(s):  
Immune Response ◽  
Targeted Delivery ◽  
Therapeutic Potential ◽  
Component Mixture ◽  
Vesicle Size ◽  
Insertion Method ◽  
Dialysis Method ◽  
Stability Issues

AbstractNano-based delivery systems have greatly enhanced our ability to administer and target drugs and macromolecules to their therapeutic targets. Oligonucleotide drugs have great therapeutic potential but have off-target effects and stability issues, so they are often encapsulated in functionalized vesicles with targeting ligands such as antibodies (Ab). Herein, we describe a novel, scalable and straightforward approach to produce functionalized vesicles called the “Functionalized Lipid Insertion Method.” This method differs significantly from an older approach referred to as the “Detergent-Dialysis Method.” The older method requires excess detergent and extensive dialysis over many hours to produce the functionalized vesicles. With the “Functionalized Lipid Insertion Method,” only the functionalized lipid is detergent-solubilized during the formation of the functionalized vesicle. The approach reduces the dialysis time, keeps the vesicle intact, and orients the functionalized lipid to improve targeting compared to the older method. The dynamic light scattering (DLS) technique demonstrated that vesicle size is sensitive to the initial detergent-solubilized component mixture by the older method. In contrast, functionalized vesicle size increases are consistent with functionalized lipid insertion into the vesicle. In vitro, functionalized vesicles using our approach are able to deliver oligonucleotides selectively and can functionally affect liver cancer HepG2 cells. Functionalized vesicles produced by this method can also achieve targeted delivery of oligonucleotides in mice without inducing a significant immune response through cytokine production or showing physical signs of an immune response. The industrial and therapeutic significance and implications of functionalized vesicles produced by our method are also discussed.

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