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.

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 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 Targeted delivery of mesoporous silica nanoparticles loaded monastrol into cancer cells: an in vitro study

2017 ◽  
Vol 7 (8) ◽  
pp. 549-555 ◽  
Author(s):  
Huzaifa Hanif ◽  
Samina Nazir ◽  
Kehkashan Mazhar ◽  
Muhammad Waseem ◽  
Shazia Bano ◽  
...  
Keyword(s):  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Mesoporous Silica Nanoparticles ◽  
In Vitro Study ◽  
Vitro Study

scholarly journals Inducing cell death in vitro in cancer cells by targeted delivery of cytochrome c via a transferrin conjugate

PLoS ONE ◽  
2018 ◽  
Vol 13 (4) ◽  
pp. e0195542 ◽  
Author(s):  
Manoj Saxena ◽  
Yamixa Delgado ◽  
Rohit Kumar Sharma ◽  
Shweta Sharma ◽  
Solimar Liz Ponce De León Guzmán ◽  
...  
Keyword(s):  
Cell Death ◽  
Cytochrome C ◽  
Cancer Cells ◽  
Targeted Delivery

scholarly journals Novel Infectivity-Enhanced Oncolytic Adenovirus with a Capsid-Incorporated Dual-Imaging Moiety for Monitoring Virotherapy in Ovarian Cancer

2009 ◽  
Vol 8 (5) ◽  
pp. 7290.2009.00025 ◽  
Author(s):  
Kristopher J. Kimball ◽  
Angel A. Rivera ◽  
Kurt R. Zinn ◽  
Mert Icyuz ◽  
Vaibhav Saini ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Fluorescent Protein ◽  
Imaging Modality ◽  
Fluorescent Microscopy ◽  
Oncolytic Adenovirus ◽  
Ovarian Cancer Cells ◽  
Microscopy Imaging ◽  
Dual Imaging

We sought to develop a cancer-targeted, infectivity-enhanced oncolytic adenovirus that embodies a capsid-labeling fusion for non-invasive dual-modality imaging of ovarian cancer virotherapy. A functional fusion protein composed of fluorescent and nuclear imaging tags was genetically incorporated into the capsid of an infectivity-enhanced conditionally replicative adenovirus. Incorporation of herpes simplex virus thymidine kinase (HSV-tk) and monomeric red fluorescent protein 1 (mRFP1) into the viral capsid and its genomic stability were verified by molecular analyses. Replication and oncolysis were evaluated in ovarian cancer cells. Fusion functionality was confirmed by in vitro gamma camera and fluorescent microscopy imaging. Comparison of tk-mRFP virus to single-modality controls revealed similar replication efficiency and oncolytic potency. Molecular fusion did not abolish enzymatic activity of HSV-tk as the virus effectively phosphorylated thymidine both ex vivo and in vitro. In vitro fluorescence imaging demonstrated a strong correlation between the intensity of fluorescent signal and cytopathic effect in infected ovarian cancer cells, suggesting that fluorescence can be used to monitor viral replication. We have in vitro validated a new infectivity-enhanced oncolytic adenovirus with a dual-imaging modality-labeled capsid, optimized for ovarian cancer virotherapy. The new agent could provide incremental gains toward climbing the barriers for achieving conditionally replicated adenovirus efficacy in human trials.

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.

scholarly journals A Novel Approach to Anticancer Therapy: Molecular Modules Based on the Barnase:Barstar Pair for Targeted Delivery of HSP70 to Tumor Cells

Acta Naturae ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 85-91 ◽  
Author(s):  
A. M. Sapozhnikov ◽  
A. V. Klinkova ◽  
O. A. Shustova ◽  
M. V. Grechikhina ◽  
M. S. Kilyachus ◽  
...  
Keyword(s):  
Immune System ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Targeted Delivery ◽  
Important Distinction ◽  
Tumor Tissues ◽  
Wide Range ◽  
Antitumor Immunotherapy ◽  
Surface Localization

One important distinction between many tumor cell types and normal cells consists in the translocation of a number of intracellular proteins, in particular the 70 kDa heat shock protein (HSP70), to the surface of the plasma membrane. It has been demonstrated that such surface localization of HSP70 on tumor cells is recognized by cytotoxic effectors of the immune system, which increases their cytolytic activity. The mechanisms behind this interaction are not fully clear; however, the phenomenon of surface localization of HSP70 on cancer cells can be used to develop new approaches to antitumor immunotherapy. At the same time, it is known that the presence of HSP70 on a cells surface is not a universal feature of cancer cells. Many types of tumor tissues do not express membrane-associated HSP70, which limits the clinical potential of these approaches. In this context, targeted delivery of exogenous HSP70 to the surface of cancer cells with the aim of attracting and activating the cytotoxic effectors of the immune system can be considered a promising means of antitumor immunotherapy. Molecular constructs containing recombinant mini-antibodies specific to tumor-associated antigens (in particular, antibodies specific to HER2/neu-antigen and other markers highly expressed on the surface of a wide range of cancer cells) can be used to target the delivery of HSP70 to tumor tissues. In order to assess the feasibility and effectiveness of this approach, recombinant constructs containing a mini-antibody specific to the HER2/ neu-antigen in the first module and HSP70 molecule or a fragment of this protein in the second module were developed in this study. Strong selective interaction between the modules was ensured by a cohesive unit formed by the barnase:barstar pair, a heterodimer characterized by an unusually high constant of association. During testing of the developed constructs in in vitro models the constructs exhibited targeted binding to tumor cells expressing the HER2/neu antigen and the agents had a significant stimulating effect on the cytotoxic activity of NK cells against the respective cancer cells.

scholarly journals Precise and Efficient Phototheranostics: Molecular Engineering of Photosensitizers with Near-Infrared Aggregation-Induced Emission for Acid-Triggered Nucleus-Targeted Photodynamic Cancer Therapy

2020 ◽  
Author(s):  
Zhijun Zhang ◽  
Wenhan XU ◽  
Peihong Xiao ◽  
Miaomiao Kang ◽  
Dingyuan Yan ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Targeted Delivery ◽  
Near Infrared ◽  
Fluorescence Emission ◽  
Molecular Engineering ◽  
Ros Generation ◽  
Subcellular Targeting ◽  
Aggregation Induced Emission ◽  
Photodynamic Cancer Therapy

Phototheranostics involving both fluorescence imaging (FLI) and photodynamic therapy (PDT) has been recognized to be potentially powerful for cancer treatment by virtue of various intrinsic advantages. However, the state-of-the-art materials in this area are still far from ideal towards practical applications, owing to their respective and collective drawbacks, such as inefficient imaging quality, inferior reactive oxygen species (ROS) production, the lack of subcellular-targeting capability, and dissatisfactory theranostics delivery. In this contribution, these shortcomings are successfully addressed through the integration of finely engineered photosensitizers having aggregation-induced emission (AIE) features and well tailored nanocarrier system. The yielded AIE NPs simultaneously exhibit broad absorption in visible light region, bright near-infrared fluorescence emission, extremely high ROS generation, as well as tumor lysosomal acidity-activated and nucleus-targeted delivery functions, making them dramatically promising for precise and efficient phototheranostics. Both in vitro and in vivo evaluations show that the presented nanotheranostic system bearing excellent photostability and appreciable biosecurity well performed in FLI-guided photodynamic cancer therapy. This study thus not only extends the applications scope of AIE nanomaterials, but also offers useful insights into constructing a new generation of cancer theranostics.

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