scholarly journals Folate-Targeted Curcumin-Encapsulated Micellar Nanosystem for Chemotherapy and Curcumin-Mediated Photodynamic Therapy

Polymers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2280
Author(s):  
Yun Hsuan Lin ◽  
Ching-Yi Chen
Keyword(s):  
Photodynamic Therapy ◽  
Cancer Cells ◽  
High Efficiency ◽  
Folate Receptor ◽  
Drug Loading ◽  
Aqueous Solubility ◽  
Polymeric Micelle ◽  
In Vitro Cytotoxicity ◽  
Efficient Delivery

Curcumin (CUR) is a natural phenolic product used as a high-efficiency and low-toxicity anticancer drug and photosensitizer. However, it has a poor aqueous solubility and a lack of target specificity, which limits its clinical applications. Hence, we developed a folate-conjugated polymeric micelle to enhance the efficient delivery of CUR for effective cancer cell targeting and anticancer efficiency. A series of biocompatible folate-conjugated poly(2-(methacryloyloxy)ethylphosphoryl- choline)-b-poly(ε-caprolactone) (FPM) was synthesized with different hydrophobic lengths and folate contents. The prepared CUR-loaded micelles (CUR-FPM) possessed several superior properties, including an excellent drug loading capacity (6.3 ± 1.2%), improved CUR aqueous stability, fast-sustained CUR release in an acidic environment, and efficient intracellular production of reactive oxygen species. The in vitro cytotoxicity demonstrated that the CUR-FPM micelles efficiently suppressed the growth of HeLa cells (folate-receptor overexpression) compared to that of HT-29 cells, and a competition study showed less cytotoxic effect when free folic acid blocked the folate receptor, indicating the folate conjugation played the role of targeting the specific cells well. Moreover, the CUR-mediated photodynamic therapy (PDT) by CUR-FPM micelles under irradiation further inhibited the proliferation of cancer cells. All these results indicate that the CUR-FPM micelles could be a promising delivery system for folate-overexpressing cancer cells, complementary chemotherapy, and CUR-mediated photodynamic therapy.

scholarly journals Biotin-Decorated PAMAM G4.5 Dendrimer Nanoparticles to Enhance the Delivery, Anti-Proliferative, and Apoptotic Effects of Chemotherapeutic Drug in Cancer Cells

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 443 ◽  
Author(s):  
Endiries Yibru Hanurry ◽  
Tefera Worku Mekonnen ◽  
Abegaz Tizazu Andrgie ◽  
Haile Fentahun Darge ◽  
Yihenew Simegniew Birhan ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cell Viability ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cellular Uptake ◽  
Drug Loading ◽  
In Vitro Cytotoxicity ◽  
Amide Bond ◽  
Solid Cancer

Biotin receptors are overexpressed by various types of solid cancer cells and play a significant role in tumor metabolism, growth, and metastasis. Thus, targeting the biotin receptors on tumor cells may enhance the efficiency and reduce the side-effects of chemotherapy. The aim of this study was to develop a biotin-coupled poly(amido)amine (PAMAM) (PG4.5) dendrimer nanoparticle to enhance the tumor-specific delivery and intracellular uptake of anticancer drugs via receptor-mediated endocytosis. We modified PG4.5 with diethylenetriamine (DETA) followed by biotin via an amide bond and characterized the resulting PG4.5-DETA-biotin nanoparticles by 1H NMR, FTIR, and Raman spectroscopy. Loading and releasing of gemcitabine (GEM) from PG4.5-DETA-biotin were evaluated by UV–Visible spectrophotometry. Cell viability and cellular uptake were examined by MTT assay and flow cytometry to assess the biocompatibility, cellular internalization efficiency and antiproliferative activity of PG4.5-DETA-biotin/GEM. Gemcitabine-loaded PG4.5-DETA-biotin nanoparticles were spherical with a particle size of 81.6 ± 6.08 nm and zeta potential of 0.47 ± 1.25 mV. Maximum drug-loading content and encapsulation efficiency were 10.84 ± 0.16% and 47.01 ± 0.71%, respectively. Nearly 60.54 ± 1.99% and 73.96 ± 1.14% of gemcitabine was released from PG4.5-DETA-biotin/GEM nanoparticles after 48 h at the acidic pH values of 6.5 and 5, respectively. Flow cytometry and fluorescence microscopy of cellular uptake results revealed PG4.5-DETA-biotin/GEM nanoparticles selectively targeted cancer cells in vitro. Cytotoxicity assays demonstrated gemcitabine-loaded PG4.5-DETA-biotin significantly reduced cell viability and induced apoptosis in HeLa cells. Thus, biotin-coupled PG4.5-DETA nanocarrier could provide an effective, targeted drug delivery system and selectively convey gemcitabine into tumor cells.

scholarly journals Lipid-polymer hybrid nanoparticles carrying doxorubicin and edelfosine combo for synergistic anticancer effect against drug-resistant Osteosarcoma

2020 ◽  
Author(s):  
Ping Yang ◽  
Lian Zhang ◽  
Tian Wang ◽  
Qi Liu ◽  
Jing Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Folate Receptor ◽  
Drug Loading ◽  
Hybrid Nanoparticles ◽  
Anticancer Efficacy ◽  
Targeted Nanoparticles ◽  
Polymer Hybrid ◽  
Multiple Drugs

Abstract In this study, we have prepared a novel folate receptor-targeted doxorubicin (DOX) and edelfosine (ET)-loaded lipid polymer hybrid nanoparticle to enhance the anticancer efficacy in osteosarcoma. The dual-drug loaded nanoparticles showed a nanosized morphology and physiological stability. The targeted nanoparticles showed enhanced cellular internalization and subcellular distribution in MG63 cancer cells compared to that of non-targeted nanoparticles. Among many ratios of DOX and ET, 1:1 ratiometric combinations of drugs were observed to be highly synergistic in killing the cancer cells. MTT assay and caspase-3/7 activity assay clearly showed the superior anticancer efficacy of DE-FPLN formulations in inducing the cancer cell death. In vitro results indicate that the co-administration of two drugs in a folic acid-targeted nanoparticle could potentially induce the apoptosis and cell death. In vivo results displayed the potency of tumor cell killing and significant suppression of tumor growth without any detectable side effects. The lipid polymer hybrid nanocarriers with multiple properties of high drug loading, sequential and ratiometric drug release, improved physiological stability, prolonged blood circulation, and tumor-specific targeting are promising for the delivery of multiple drugs in the treatment of osteosarcoma.

The Effect of Phase Transition Temperature on Therapeutic Efficacy of Liposomal Bortezomib

2020 ◽  
Vol 20 (6) ◽  
pp. 700-708
Author(s):  
Mitra Korani ◽  
Sara Nikoofal-Sahlabadi ◽  
Amin R. Nikpoor ◽  
Solmaz Ghaffari ◽  
Hossein Attar ◽  
...  
Keyword(s):  
Side Effects ◽  
Cell Line ◽  
Therapeutic Efficacy ◽  
Drug Loading ◽  
Particle Diameter ◽  
In Vitro Cytotoxicity ◽  
Liposomal Formulations ◽  
Cytotoxicity Studies ◽  
Anti Tumor Activity

Aims: Here, three liposomal formulations of DPPC/DPPG/Chol/DSPE-mPEG2000 (F1), DPPC/DPPG/Chol (F2) and HSPC/DPPG/Chol/DSPE-mPEG2000 (F3) encapsulating BTZ were prepared and characterized in terms of their size, surface charge, drug loading, and release profile. Mannitol was used as a trapping agent to entrap the BTZ inside the liposomal core. The cytotoxicity and anti-tumor activity of formulations were investigated in vitro and in vivo in mice bearing tumor. Background: Bortezomib (BTZ) is an FDA approved proteasome inhibitor for the treatment of mantle cell lymphoma and multiple myeloma. The low solubility of BTZ has been responsible for the several side effects and low therapeutic efficacy of the drug. Encapsulating BTZ in a nano drug delivery system; helps overcome such issues. Among NDDSs, liposomes are promising diagnostic and therapeutic delivery vehicles in cancer treatment. Objective: Evaluating anti-tumor activity of bortezomib liposomal formulations. Methods: Data prompted us to design and develop three different liposomal formulations of BTZ based on Tm parameter, which determines liposomal stiffness. DPPC (Tm 41°C) and HSPC (Tm 55°C) lipids were chosen as variables associated with liposome rigidity. In vitro cytotoxicity assay was then carried out for the three designed liposomal formulations on C26 and B16F0, which are the colon and melanoma cancer mouse-cell lines, respectively. NIH 3T3 mouse embryonic fibroblast cell line was also used as a normal cell line. The therapeutic efficacy of these formulations was further assessed in mice tumor models. Result: MBTZ were successfully encapsulated into all the three liposomal formulations with a high entrapment efficacy of 60, 64, and 84% for F1, F2, and F3, respectively. The findings showed that liposomes mean particle diameter ranged from 103.4 to 146.8nm. In vitro cytotoxicity studies showed that liposomal-BTZ formulations had higher IC50 value in comparison to free BTZ. F2-liposomes with DPPC, having lower Tm of 41°C, showed much higher anti-tumor efficacy in mice models of C26 and B16F0 tumors compared to F3-HSPC liposomes with a Tm of 55°C. F2 formulation also enhanced mice survival compared with untreated groups, either in BALB/c or in C57BL/6 mice. Conclusion: Our findings indicated that F2-DPPC-liposomal formulations prepared with Tm close to body temperature seem to be effective in reducing the side effects and increasing the therapeutic efficacy of BTZ and merits further investigation.

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.

scholarly journals Alkynyl N-BODIPYs as Reactive Intermediates for the Development of Dyes for Biophotonics

2020 ◽  
Vol 3 (1) ◽  
pp. 15
Author(s):  
César Ray ◽  
Andrés García-Sampedro ◽  
Christopher Schad ◽  
Edurne Avellanal-Zaballa ◽  
Florencio Moreno ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Photodynamic Therapy ◽  
Click Chemistry ◽  
Cancer Cells ◽  
Reactive Intermediates ◽  
New Approach ◽  
Pancreatic Cancer Cells ◽  
Bio Imaging

A new approach for the rapid multi-functionalization of BODIPY dyes towards biophotonics is reported. It is based on novel N-BODIPYs, through reactive intermediates with alkynyl groups to be further derivatized by click chemistry. This approach has been exemplified by the development of new dyes for cell bio-imaging, which have proven to successfully internalize into pancreatic cancer cells and accumulate in the mitochondria. The in vitro suitability for photodynamic therapy (PDT) was also analyzed and confirmed our compounds to be promising PDT candidates for the treatment of pancreatic cancer.

scholarly journals An Efficient Photodynamic Therapy Treatment for Human Pancreatic Adenocarcinoma

2020 ◽  
Vol 9 (1) ◽  
pp. 192 ◽  
Author(s):  
Alexandre Quilbe ◽  
Olivier Moralès ◽  
Martha Baydoun ◽  
Abhishek Kumar ◽  
Rami Mustapha ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Photodynamic Therapy ◽  
Immune System ◽  
Cancer Cells ◽  
Pancreatic Adenocarcinoma ◽  
Cell Lines ◽  
Folate Receptor ◽  
Mice Model ◽  
Gene And Protein Expression ◽  
The Impact

To date, pancreatic adenocarcinoma (ADKP) is a devastating disease for which the incidence rate is close to the mortality rate. The survival rate has evolved only 2–5% in 45 years, highlighting the failure of current therapies. Otherwise, the use of photodynamic therapy (PDT), based on the use of an adapted photosensitizer (PS) has already proved its worth and has prompted a growing interest in the field of oncology. We have developed a new photosensitizer (PS-FOL/PS2), protected by a recently published patent (WO2019 016397-A1, 24 January 2019). This photosensitizer is associated with an addressing molecule (folic acid) targeting the folate receptor 1 (FOLR1) with a high affinity. Folate binds to FOLR1, in a specific way, expressed in 100% of ADKP or over-expressed in 30% of cases. The first objective of this study is to evaluate the effectiveness of this PS2-PDT in four ADKP cell lines: Capan-1, Capan-2, MiapaCa-2, and Panc-1. For this purpose, we first evaluated the gene and protein expression of FOLR1 on four ADKP cell lines. Subsequently, we evaluated PS2’s efficacy in our cell lines and we assessed the impact of PDT on the secretome of cancer cells and its impact on the immune system. Finally, we evaluate the PDT efficacy on a humanized SCID mouse model of pancreatic cancer. In a very interesting way, we observed a significant increase in the proliferation of activated-human PBMC when cultured with conditioned media of ADKP cancer cells subjected to PDT. Furthermore, to evaluate in vivo the impact of this new PS, we analyzed the tumor growth in a humanized SCID mice model of pancreatic cancer. Four conditions were tested: Untreated, mice (nontreated), mice with PS (PS2), mice subjected to illumination (Light only), and mice subjected to illumination in the presence of PS (PDT). We noticed that the mice subjected to PDT presented a strong decrease in the growth of the tumor over time after illumination. Our investigations have not only suggested that PS2-PDT is an effective therapy in the treatment of PDAC but also that it activates the immune system and could be considered as a real adjuvant for anti-cancer vaccination. Thus, this new study provides new treatment options for patients in a therapeutic impasse and will provide a new arsenal in the fight against PDAC.

Oxovanadium(IV) complexes with tetradentate thiosemicarbazones. Synthesis, characterization, anticancer enzyme inhibition and in vitro cytotoxicity on breast cancer cells

Polyhedron ◽  
2021 ◽  
Vol 202 ◽  
pp. 115192
Author(s):  
Onur Ertik ◽  
Ferdane Danışman Kalındemirtaş ◽  
Büşra Kaya ◽  
Refiye Yanardag ◽  
Serap Erdem Kuruca ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Enzyme Inhibition ◽  
Breast Cancer Cells ◽  
In Vitro Cytotoxicity

scholarly journals Gold(I) Complexes with P-Donor Ligands and Their Biological Evaluation

Processes ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 2100
Author(s):  
Monika Richert ◽  
Renata Mikstacka ◽  
Mariusz Walczyk ◽  
Marcin Janusz Cieślak ◽  
Julia Kaźmierczak-Barańska ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Umbilical Vein ◽  
Biological Properties ◽  
Biological Evaluation ◽  
In Vitro Cytotoxicity ◽  
Myelogenous Leukemia ◽  
31P Nmr Spectroscopy ◽  
Cervix Carcinoma ◽  
Ovarian Carcinoma Cell Line

Gold(I) complexes with phosphine ligands—[Au(TrippyPhos)Cl] (1) (TrippyPhos = 1-[2-[bis(tert-butyl)phosphino]phenyl]-3,5-diphenyl-1H-pyrazole), [Au(BippyPhos)Cl]0.5CH2Cl2 (2) (BippyPhos = 5-(di-tert-butylphosphino)-1′, 3′, 5′-triphenyl-1′H-[1,4′]bipyrazole), and [Au(meCgPPh)Cl] (3) (meCgPPh = 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantane—were investigated as types of bioactive gold metallodrugs. Complexes (1)–(3) were characterized using IR, 1H, 13C, 31P NMR spectroscopy, elemental analysis and mass spectrometry (FAB-MS). Complexes of (1) and (2) exhibited substantial in vitro cytotoxicity (IC50 = 0.5–7.0 μM) against both the cisplatin-sensitive and -resistant variants of the A2780 human ovarian carcinoma cell line, as well as against the A549 human lung carcinoma, K562 chronic myelogenous leukemia, and HeLa (human cervix carcinoma) cells. However, among the compounds studied, complex (2) showed the most promising biological properties: the highest stability in biologically relevant media, selectivity towards cancer cells over the non-cancer cells (HUVEC, human umbilical vein endothelial cells), and the highest inhibitory effect on cytosolic NADPH-dependent reductases in A2780 and A2780cis cells among the gold complexes under analysis.

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.

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