Unimolecular micelles of pH-responsive star-like copolymers for co-delivery of anticancer drugs and small-molecular photothermal agents: a new drug-carrier for combinational chemo/photothermal cancer therapy

2017 ◽  
Vol 5 (43) ◽  
pp. 8514-8524 ◽  
Author(s):  
Tao Jia ◽  
Shuo Huang ◽  
Cangjie Yang ◽  
Mingfeng Wang
Keyword(s):  
Cancer Therapy ◽  
Cancer Cells ◽  
Therapeutic Effect ◽  
Anticancer Drugs ◽  
Drug Carrier ◽  
Ph Responsive ◽  
New Drug

Robust unimolecular micelles of amphiphilic pH-responsive starlike copolymers that carry anticancer drugs and photothermal agents show enhanced therapeutic effect against cancer cells.

scholarly journals Bioinformatic Analysis of the Nicotinamide Binding Site in Poly(ADP-Ribose) Polymerase Family Proteins

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1201
Author(s):  
Garri Manasaryan ◽  
Dmitry Suplatov ◽  
Sergey Pushkarev ◽  
Viktor Drobot ◽  
Alexander Kuimov ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Cancer Therapy ◽  
Adverse Effects ◽  
Binding Site ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Bioinformatic Analysis ◽  
Parp Inhibitors ◽  
Functional Region ◽  
D Loop

The PARP family consists of 17 members with diverse functions, including those related to cancer cells’ viability. Several PARP inhibitors are of great interest as innovative anticancer drugs, but they have low selectivity towards distinct PARP family members and exert serious adverse effects. We describe a family-wide study of the nicotinamide (NA) binding site, an important functional region in the PARP structure, using comparative bioinformatic analysis and molecular modeling. Mutations in the NA site and D-loop mobility around the NA site were identified as factors that can guide the design of selective PARP inhibitors. Our findings are of particular importance for the development of novel tankyrase (PARPs 5a and 5b) inhibitors for cancer therapy.

Antitumor efficacy of a PLGA composite nanofiber embedded with doxorubicin@MSNs and hydroxycamptothecin@HANPs

RSC Advances ◽  
2014 ◽  
Vol 4 (95) ◽  
pp. 53344-53351 ◽  
Author(s):  
Mengxia Chen ◽  
Wei Feng ◽  
Si Lin ◽  
Chuanglong He ◽  
Yu Gao ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Therapeutic Effect ◽  
Anticancer Drugs ◽  
Delivery System ◽  
Antitumor Efficacy ◽  
Composite Nanofiber

A co-delivery system with two or more anticancer drugs has been proposed to minimize the dosage of drug and to achieve the synergistic therapeutic effect in cancer therapy.

scholarly journals Synthesis of surface capped mesoporous silica nanoparticles for pH-stimuli responsive drug delivery applications

MedChemComm ◽  
2017 ◽  
Vol 8 (9) ◽  
pp. 1797-1805 ◽  
Author(s):  
Madhappan Santha Moorthy ◽  
Subramanian Bharathiraja ◽  
Panchanathan Manivasagan ◽  
Kang Dae Lee ◽  
Junghwan Oh
Keyword(s):  
Drug Delivery ◽  
Cancer Therapy ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Mesoporous Silica Nanoparticles ◽  
Drug Carrier ◽  
Stimuli Responsive ◽  
Ph Responsive ◽  
Drug Delivery Applications

Herein, we propose a “host–guest” complexation-based mesoporous silica drug carrier, MSNs@Mela@TTM, for pH-responsive drug delivery applications in cancer therapy.

Glutathione- and pH-responsive nonporous silica prodrug nanoparticles for controlled release and cancer therapy

Nanoscale ◽  
2015 ◽  
Vol 7 (13) ◽  
pp. 5859-5868 ◽  
Author(s):  
Zhigang Xu ◽  
Shiying Liu ◽  
Yuejun Kang ◽  
Mingfeng Wang
Keyword(s):  
Controlled Release ◽  
Cancer Therapy ◽  
Anticancer Drugs ◽  
Stimuli Responsive ◽  
Ph Responsive ◽  
Silica Matrices

Stimuli-responsive nonporous silica prodrug nanoparticles are developed by covalently encapsulating anticancer drugs camptothecin (CPT) and doxorubicin (DOX) into silica matrices through glutathione (GSH)-responsive disulfide and pH-responsive hydrazone bonds.

scholarly journals Stimuli-Responsive, Plasmonic Nanogel for Dual Delivery of Curcumin and Photothermal Therapy for Cancer Treatment

2021 ◽  
Vol 8 ◽  
Author(s):  
Fadak Howaili ◽  
Ezgi Özliseli ◽  
Berrin Küçüktürkmen ◽  
Seyyede Mahboubeh Razavi ◽  
Majid Sadeghizadeh ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Photothermal Therapy ◽  
Drug Carrier ◽  
Drug Loading ◽  
Stimuli Responsive ◽  
Ph Responsive ◽  
Cytotoxicity Studies

Nanogels (Ng) are crosslinked polymer-based hydrogel nanoparticles considered to be next-generation drug delivery systems due to their superior properties, including high drug loading capacity, low toxicity, and stimuli responsiveness. In this study, dually thermo-pH-responsive plasmonic nanogel (AuNP@Ng) was synthesized by grafting poly (N-isopropyl acrylamide) (PNIPAM) to chitosan (CS) in the presence of a chemical crosslinker to serve as a drug carrier system. The nanogel was further incorporated with gold nanoparticles (AuNP) to provide simultaneous drug delivery and photothermal therapy (PTT). Curcumin's (Cur) low water solubility and low bioavailability are the biggest obstacles to effective use of curcumin for anticancer therapy, and these obstacles can be overcome by utilizing an efficient delivery system. Therefore, curcumin was chosen as a model drug to be loaded into the nanogel for enhancing the anticancer efficiency, and further, its therapeutic efficiency was enhanced by PTT of the formulated AuNP@Ng. Thorough characterization of Ng based on CS and PNIPAM was conducted to confirm successful synthesis. Furthermore, photothermal properties and swelling ratio of fabricated nanoparticles were evaluated. Morphology and size measurements of nanogel were determined by transmission electron microscopy (TEM), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). Nanogel was found to have a hydrodynamic size of ~167 nm and exhibited sustained release of curcumin up to 72 h with dual thermo-pH responsive drug release behavior, as examined under different temperature and pH conditions. Cytocompatibility of plasmonic nanogel was evaluated on MDA-MB-231 human breast cancer and non-tumorigenic MCF 10A cell lines, and the findings indicated the nanogel formulation to be cytocompatible. Nanoparticle uptake studies showed high internalization of nanoparticles in cancer cells when compared with non-tumorigenic cells and confocal microscopy further demonstrated that AuNP@Ng were internalized into the MDA-MB-231 cancer cells via endosomal route. In vitro cytotoxicity studies revealed dose-dependent and time-dependent drug delivery of curcumin loaded AuNP@Ng/Cur. Furthermore, the developed nanoparticles showed an improved chemotherapy efficacy when irradiated with near-infrared (NIR) laser (808 nm) in vitro. This work revealed that synthesized plasmonic nanogel loaded with curcumin (AuNP@Ng/Cur) can act as stimuli-responsive nanocarriers, having potential for dual therapy i.e., delivery of hydrophobic drug and photothermal therapy.

scholarly journals ID: 4001 Nanoparticle-based Cancer Therapy

2017 ◽  
Vol 4 (S) ◽  
pp. 2
Author(s):  
Fuyu Tamanoi
Keyword(s):  
Magnetic Field ◽  
Iron Oxide ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Tumor Targeting ◽  
Two Photon ◽  
Pore Opening ◽  
Oscillating Magnetic Field ◽  
The Way

Advances in Nanotechnology have led to the development of a variety of nanomaterials that are changing the way cancer therapy is carried out. A particularly important example is nanoparticle that can carry cargo to tumor. We are using mesoporous silica nanoparticles (MSNs) for cancer therapy. MSNs contain thousands of pores that provide storage space for anticancer drugs. These materials are biocompatible and safe. In addition, we have recently introduced biodegradability into MSNs.  We have shown that MSNs exhibit excellent tumor targeting capability in two different animal model systems (chicken egg tumor model and mouse xenografts). This tumor targeting capability is partly due to its small size; these nano-sized particles can accumulate in tumor due to leaky tumor vasculature. In addition, we have carried out surface modifications to attach ligands that bind receptors present on the surface of cancer cells. For example, folate was attached to the surface that enables binding to folate receptors overexpressed on cancer cells.  We have also conferred controlled anticancer drug release capability to MSNs in collaboration with Fraser Stoddart and Jeff Zink. This was accomplished by attaching nanovalves at the opening of the pores. Rotaxanes and pseudorotaxanes are used to prepare nanovalves. These chemical compounds consist of a stalk and a moving part. When the moving part is close to the pore opening, the nanovalve is closed. On the other hand, when the moving part is located away from the pore opening, the nanovalve is closed. In this way, the nanovalve provides an open and close function so that controlled release of anticancer drugs can be carried out.  Light activated nanovalves were developed by incorporating azobenzene into nanovalves. Azobenzene changes conformation upon light exposure and this conformational change opens the nanovalve releasing anticancer drugs in a power and exposure time dependent manner. More recently, this system was modified by incorporating two-photon dyes that can capture energy from two-photon light and transfer to azobenzene to drive the release of anticancer drugs. This enables the system to work with tissue penetrating two-photon light.  We have also developed nanoparticles that respond to oscillating magnetic field. This system was developed using MSNs that contain iron oxide core. Because of superparamagnetic property of iron oxide, the internal temperature of such nanoparticles increases when exposed to oscillating magnetic field. This temperature increase drives opening of nanovalves that are particularly designed for this purpose.   Development of nanoparticles that respond to external cues such as light and magnetic field may change the way cancer therapy is carried out. Implications on the future of cancer therapy will be discussed.

scholarly journals Mitochondria-targeted accumulation of oxygen-irrelevant free radicals for enhanced synergistic low-temperature photothermal and thermodynamic therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hongzhi Hu ◽  
Xiangtian Deng ◽  
Qingcheng Song ◽  
Wenbo Yang ◽  
Yiran Zhang ◽  
...  
Keyword(s):  
Free Radicals ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Therapeutic Effect ◽  
Xenograft Model ◽  
Dual Responsive ◽  
Cancer Cell Death ◽  
Azo Initiator

Abstract Background Although lower temperature (< 45 °C) photothermal therapy (LPTT) have attracted enormous attention in cancer therapy, the therapeutic effect is still unsatisfying when applying LPTT alone. Therefore, combining with other therapies is urgently needed to improve the therapeutic effect of LPTT. Recently reported oxygen-irrelevant free radicals based thermodynamic therapy (TDT) exhibit promising potential for hypoxic tumor treatment. However, overexpression of glutathione (GSH) in cancer cells would potently scavenge the free radicals before their arrival to the specific site and dramatically diminish the therapeutic efficacy. Methods and results In this work, a core–shell nanoplatform with an appropriate size composed of arginine–glycine–aspartate (RGD) functioned polydopamine (PDA) as a shell and a triphenylphosphonium (TPP) modified hollow mesoporous manganese dioxide (H-mMnO2) as a core was designed and fabricated for the first time. This nanostructure endows a size-controllable hollow cavity mMnO2 and thickness-tunable PDA layers, which effectively prevented the pre-matured release of encapsulated azo initiator 2,2′-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIBI) and revealed pH/NIR dual-responsive release performance. With the mitochondria-targeting ability of TPP, the smart nanocomposites (AIBI@H-mMnO2-TPP@PDA-RGD, AHTPR) could efficiently induce mitochondrial associated apoptosis in cancer cells at relatively low temperatures (< 45 °C) via selectively releasing oxygen-irrelevant free radicals in mitochondria and facilitating the depletion of intracellular GSH, exhibiting the advantages of mitochondria-targeted LPTT/TDT. More importantly, remarkable inhibition of tumor growth was observed in a subcutaneous xenograft model of osteosarcoma (OS) with negligible side effects. Conclusions The synergistic therapy efficacy was confirmed by effectively inducing cancer cell death in vitro and completely eradicating the tumors in vivo. Additionally, the excellent biosafety and biocompatibility of the nanoplatforms were confirmed both in vitro and in vivo. Taken together, the current study provides a novel paradigm toward oxygen-independent free-radical-based cancer therapy, especially for the treatment of hypoxic solid tumors. Graphical Abstract

scholarly journals Biocompatible pH-responsive nanoparticles with a core-anchored multilayer shell of triblock copolymers for enhanced cancer therapy

2017 ◽  
Vol 5 (23) ◽  
pp. 4421-4425 ◽  
Author(s):  
Elizabeth Ellis ◽  
Kangyi Zhang ◽  
Qianyu Lin ◽  
Enyi Ye ◽  
Alessandro Poma ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Cancer Cells ◽  
Self Assembly ◽  
Triblock Copolymers ◽  
Drug Efficacy ◽  
Multilayer Shell ◽  
Ph Responsive ◽  
Drug Nanocarriers ◽  
Excellent Stability

pH-Responsive drug nanocarriers were made via facile self-assembly, showing excellent stability in bio-media (50% PBS/FBS) and enhanced drug efficacy towards cancer cells.

Tumor-Targeting Peptide Conjugated pH-Responsive Micelles as a Potential Drug Carrier for Cancer Therapy

2010 ◽  
Vol 21 (2) ◽  
pp. 208-213 ◽  
Author(s):  
Xiang Lan Wu ◽  
Jong Ho Kim ◽  
Heebeom Koo ◽  
Sang Mun Bae ◽  
Hyeri Shin ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Tumor Targeting ◽  
Drug Carrier ◽  
Potential Drug ◽  
Ph Responsive ◽  
Targeting Peptide ◽  
Tumor Targeting Peptide
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