Novel Mitochondrial Targeting Multifunctional Surface Charge-Reversal Polymeric Nanoparticles for Cancer Treatment

2019 ◽  
Vol 15 (11) ◽  
pp. 2151-2163 ◽  
Author(s):  
Lei Fang ◽  
Huaying Fan ◽  
Chunjing Guo ◽  
Linhan Cui ◽  
Peng Zhang ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Targeted Delivery ◽  
Polymeric Nanoparticles ◽  
In Vitro Cytotoxicity ◽  
Hydrodynamic Diameter ◽  
Mitochondrial Targeting ◽  
Anticancer Activities ◽  
Charge Reversal

Polymeric nanoparticles were widely used as delivery vehicles for targeted delivery of anticancer drugs, because of their targeting property and versatility. Mitochondria are one of the important organelles that regulate the apoptosis of cancer cells and can be considered as a pivotal target for cancer treatment. A pH-responsive charge-reversal and mitochondrial targeting nanoparticles, Vitamin B6-oligomeric hyaluronic acid-dithiodipropionic acid-berberine (B6-oHA-SS-Ber), were prepared in this study. Ber is a lipophilic cation that was conjugated with oHA through disulfide bonds to produce mitochondria-targeted conjugates (oHA-SS-Ber). B6 was conjugated to oHA to obtain B6-oHA-SS-Ber and the two types of Cur-loaded nanoparticles (Cur-NPs) were formulated by the dialysis method. Due to pKa of B6, the charge they carried in the tumor tissue acidic microenvironment can be transferred from negative charge to positive charge, further targeting mitochondria. In our study, we successfully synthesized B6-HA-SS-Ber and characterized the structure by 1H-NMR. According to the results of transmission electron microscopy (TEM), we found that the B6-oHA-SS-Ber/Cur micelles could self-assembled in water to form spherical nanoparticles, with a hydrodynamic diameter of 172.9±13 nm. Moreover, in vitro cytotoxicity, cellular uptake, lysosome escape and mitochondrial distribution researches revealed the better effect of B6-oHA-SS-Ber/Cur micelles in comparison to oHA-SS-Ber/Cur. In vivo anticancer activities indicated that the B6-oHA-SS-Ber/Cur micelles exhibited effective inhibition of tumor growth.

SN38 polymeric nanoparticles: In vitro cytotoxicity and in vivo antitumor efficacy in xenograft balb/c model with breast cancer versus irinotecan

2014 ◽  
Vol 471 (1-2) ◽  
pp. 485-497 ◽  
Author(s):  
Nima Sepehri ◽  
Hasti Rouhani ◽  
Faranak Tavassolian ◽  
Hamed Montazeri ◽  
Mohammad Reza Khoshayand ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Polymeric Nanoparticles ◽  
In Vitro Cytotoxicity ◽  
Antitumor Efficacy

scholarly journals Targeted Delivery System of Nanobiomaterials in Anticancer Therapy: From Cells to Clinics

2014 ◽  
Vol 2014 ◽  
pp. 1-23 ◽  
Author(s):  
Su-Eon Jin ◽  
Hyo-Eon Jin ◽  
Soon-Sun Hong
Keyword(s):  
Anticancer Drugs ◽  
Targeted Delivery ◽  
Polymeric Nanoparticles ◽  
Anticancer Therapy ◽  
Delivery Systems ◽  
Specific Receptors ◽  
Targeted Delivery System ◽  
Targeted Delivery Systems

Targeted delivery systems of nanobiomaterials are necessary to be developed for the diagnosis and treatment of cancer. Nanobiomaterials can be engineered to recognize cancer-specific receptors at the cellular levels and to deliver anticancer drugs into the diseased sites. In particular, nanobiomaterial-based nanocarriers, so-called nanoplatforms, are the design of the targeted delivery systems such as liposomes, polymeric nanoparticles/micelles, nanoconjugates, norganic materials, carbon-based nanobiomaterials, and bioinspired phage system, which are based on the nanosize of 1–100 nm in diameter. In this review, the design and the application of these nanoplatforms are discussed at the cellular levels as well as in the clinics. We believe that this review can offer recent advances in the targeted delivery systems of nanobiomaterials regardingin vitroandin vivoapplications and the translation of nanobiomaterials to nanomedicine in anticancer therapy.

scholarly journals Anticancer Efficacy of Cordyceps militaris Ethanol Extract in a Xenografted Leukemia Model

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Jae Gwang Park ◽  
Young-Jin Son ◽  
Tae Ho Lee ◽  
Nam Joon Baek ◽  
Deok Hyo Yoon ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Caspase 3 ◽  
In Vitro Cytotoxicity ◽  
Cordyceps Militaris ◽  
C6 Glioma Cells ◽  
Control Group ◽  
Therapeutic Effects ◽  
Anticancer Activities

Cordyceps militaris is used widely as a traditional medicine in East Asia. Although a few studies have attempted to elucidate the anticancer activities of C. militaris, the precise mechanism of C. militaris therapeutic effects is not fully understood. We examined the anticancer activities of C. militaris ethanolic extract (Cm-EE) and its cellular and molecular mechanisms. For this purpose, a xenograft mouse model bearing murine T cell lymphoma (RMA) cell-derived cancers was established to investigate in vivo anticancer mechanisms. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, immunoblotting analysis, and flow cytometric assay were employed to check in vitro cytotoxicity, molecular targets, and proapoptotic action of Cm-EE. Interestingly, cancer sizes and mass were reduced in a C. militaris-administered group. Levels of the phosphorylated forms of p85 and AKT were clearly decreased in the group administered with Cm-EE. This result indicated that levels of phosphoglycogen synthase kinase 3β (p-GSK3β) and cleaved caspase-3 were increased with orally administered Cm-EE. In addition, Cm-EE directly inhibited the viability of cultured RMA cells and C6 glioma cells. The number of proapoptotic cells was significantly increased in a Cm-EE treated group compared with a control group. Our results suggested that C. militaris might be able to inhibit cancer growth through regulation of p85/AKT-dependent or GSK3β-related caspase-3-dependent apoptosis.

scholarly journals Preparation and Characterization of Curcumin Loaded Dextrin Sulfate- Chitosan Nanoparticles for Promoting Curcumin Anticancer Activity

2019 ◽  
Vol 16 (1) ◽  
pp. 185-195
Author(s):  
Nihal S Elbialy
Keyword(s):  
Cancer Cells ◽  
Polymeric Nanoparticles ◽  
Drug Carrier ◽  
Chitosan Nanoparticles ◽  
In Vitro Cytotoxicity ◽  
Hydrodynamic Diameter ◽  
Transmission Electron ◽  
Hct 116 ◽  
Nano Formulation

Curcumin as a natural medicinal agent has been proved to kill cancer cells effectively. However, its biomedical applications have been hindered owing to its poor bioavailability. Many nanoparticulate systems have been introduced to overcome this problem. Among this types polymeric-based nanoparticles which exhibit unique properties allowing their use as a efficient drug carrier. Developing a polymeric- blend nanoparticles will offer a promising nanocarrier with excellent biocompatibility, biodegradability and low immunogencity. In this study, curcumin nano-vehicle has been made up by combining dextren sulfate and chitosan (DSCSNPs). DSCSNPs have been characterized using different techniques. Transmission electron microscopy (TEM) which revealed the spherical, smooth surface of the nano-formulation. Dynamic light scattering (DLS) for measuring DSCSNPs hydrodynamic- diameter. Zeta potential measurements showed nanoparticles high stability. Fourier transform infrared spectroscopy (FTIR) confirmed  successful combination between the two polymers and curcumin loading on naoparticles surface. Curcumin release profile out of DSCSNPs showed high drug release in tumor acidic microenvironment. In vitro cytotoxicity measurements demonstrated that curcumin loaded polymeric nanoparticles (DSCSNPs-Cur) have high therapeutic efficacy against colon (HCT-116) and breast  (MCF-7) cancer cells compared with free curcumin.  DSCSNPs as a combined biopolymers is an excellent candidate for improving curcumin bioavailability  allowing its use as anticancer  agent.

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.

Chemotherapeutic potential of L-carnosine from stimuli-responsive magnetic nanoparticles against breast cancer model

Nanomedicine ◽  
2020 ◽  
Vol 15 (9) ◽  
pp. 891-911
Author(s):  
Ragwa M Farid ◽  
Passent M E Gaafar ◽  
Heba A Hazzah ◽  
Maged W Helmy ◽  
Ossama Y Abdallah
Keyword(s):  
Magnetic Nanoparticles ◽  
Targeted Delivery ◽  
Physicochemical Characterization ◽  
Tumor Model ◽  
Entrapment Efficiency ◽  
In Vitro Cytotoxicity ◽  
Scanning Calorimetry ◽  
Chemotherapeutic Activity

Aim: L-carnosine-coated magnetic nanoparticles (CCMNPs) were developed to enhance chemotherapeutic activity of carnosine-dipeptide. Materials & methods: Surface grafting of MNPs with carnosine was contended by differential scanning calorimetry, infrared spectroscopy and x-ray diffraction. Physicochemical characterization and in vitro cytotoxicity on MCF-7 cell line was carried out. In vivo chemotherapeutic activity and toxicity was assessed by an Ehrlich Ascites tumor model. Results: CCMNPs possessed monodispersed size (120 nm), ζ (-27.3 mV), magnetization (51.52 emu/g) and entrapment efficiency (88.3%) with sustained release rate. CCMNPs showed 2.3-folds lower IC50 values compared with carnosine solution after 48 h. Targeted CCMNPs were specifically accumulated in tumor showing significant reduction in tumor size with no systemic toxicity. Significant reduction in VEGF and cyclin D1 levels were observed. Conclusion: The developed system endowed with responsiveness to an external stimulus can represent a promising magnetically targeted delivery system for carnosine site specific delivery.

scholarly journals NIR Light-Triggered Chemo-Phototherapy by ICG Functionalized MWNTs for Synergistic Tumor-Targeted Delivery

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2145
Author(s):  
Lu Tang ◽  
Aining Zhang ◽  
Yijun Mei ◽  
Qiaqia Xiao ◽  
Xiangting Xu ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Targeted Delivery ◽  
Near Infrared ◽  
Drug Carrier ◽  
Tumor Growth Inhibition ◽  
In Vivo Experiments ◽  
Promising Application ◽  
Targeting Ability

The combinational application of photothermal therapy (PTT), chemotherapy, and nanotechnology is a booming therapeutic strategy for cancer treatment. Multi-walled carbon nanotube (MWNT) is often utilized as drug carrier in biomedical fields with excellent photothermal properties, and indocyanine green (ICG) is a near-infrared (NIR) dye approved by FDA. In addition, ICG is also a photothermal agent that can strongly absorb light energy for tumor ablation. Herein, we explored a synergistic strategy by connecting MWNT and a kind of ICG derivate ICG-NH2 through hyaluronic acid (HA) that possesses CD44 receptor targeting ability, which largely enhanced the PTT effect of both MWNT and ICG-NH2. To realize the synergistic therapeutic effect of chemotherapy and phototherapy, doxorubicin (DOX) was attached on the wall of MWNT via π–π interaction to obtain the final MWNT-HA-ICG/DOX nanocomplexes. Both in vitro and in vivo experiments verified the great therapeutic efficacy of MWNT-HA-ICG/DOX nanocomplexes, which was characterized by improved photothermal performance, strengthened cytotoxicity, and elevated tumor growth inhibition based on MCF-7 tumor models. Therefore, this synergistic strategy we report here might offer a new idea with promising application prospect for cancer treatment.

Dequalinium-derived nanoconstructs: A promising vehicle for mitochondrial targeting

2021 ◽  
Vol 18 ◽  
Author(s):  
Abhishek Pawar ◽  
Swati Korake ◽  
Kavita R. Gajbhiye
Keyword(s):  
Drug Targeting ◽  
Polymeric Nanoparticles ◽  
Pharmaceutical Formulations ◽  
Mitochondrial Targeting ◽  
Power House ◽  
Therapeutic Molecules ◽  
Dequalinium Chloride ◽  
And Function

Abstract: The power house of the cell; mitochondrion, is a vital organelle for drug targeting in the treatment of many diseases owing to its fundamental duties and function related to cell proliferation and death. The mitochondrial membrane comprises bilayer artifact and pose extremely negative potential which create hurdle for therapeutic molecules in reaching mitochondria. To accomplish mitochondrial targeting, the scientific community has explored diverse pharmaceutical formulations like liposomes, polymeric nanoparticles (NPs), and inorganic NPs. However, the game changing technology was modification of these carriers by mitochondriotropic moiety, dequalinium chloride (DQA) or delivering the chemotherapeutics by DQAsomes. The DQA represents a distinctive mitochondriotropic delocalized cation that display their selectivity towards accumulation in mitochondria of carcinoma cell. Attributed to this characteristics, DQAsomes have been formulated using DQA and explored for successful mitochondrial targeting of bioactives. In this review, we have discussed the effectiveness of DQA nanocarriers which efficiently and selectively transmit the cytotoxic drug to the tumor cell. The DQA based nanoformulations have evidently displayed augmented pharmacological and therapeutic outcome than their counterparts both in vitro and in vivo. Thus, DQAsomes symbolizes an ideal carrier with excellent potential as mitochondial targeting agent.

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