scholarly journals Apoptotic body–mediated intercellular delivery for enhanced drug penetration and whole tumor destruction

2021 ◽  
Vol 7 (16) ◽  
pp. eabg0880
Author(s):  
Dongyang Zhao ◽  
Wenhui Tao ◽  
Songhao Li ◽  
Yao Chen ◽  
Yinghua Sun ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Chemotherapeutic Agents ◽  
Deep Penetration ◽  
Drug Penetration ◽  
Apoptotic Bodies ◽  
Apoptotic Body ◽  
Tumor Penetration ◽  
Tumor Destruction ◽  
Low Toxicity ◽  
Hypoxic Tumor

Chemotherapeutic nanomedicines can exploit the neighboring effect to increase tumor penetration. However, the neighboring effect is limited, likely by the consumption of chemotherapeutic agents and resistance of internal hypoxic tumor cells. Here, we first propose and demonstrate that apoptotic bodies (ApoBDs) could carry the remaining drugs to neighboring tumor cells after apoptosis. To enhance the ApoBD-based neighboring effect, we fabricated disulfide-linked prodrug nanoparticles consisting of camptothecin (CPT) and hypoxia-activated prodrug PR104A. CPT kills external normoxic tumor cells to produce ApoBDs, while PR104A remains inactive. The remaining drugs could be effectively delivered into internal tumor cells via ApoBDs. Although CPT exhibits low toxicity to internal hypoxic tumor cells, PR104A could be activated to exert strong cytotoxicity, which further facilitates deep penetration of the remaining drugs. Such a synergic approach could overcome the limitations of the neighboring effect to penetrate deep into solid tumors for whole tumor destruction.

Hybrid Compounds & Oxidative Stress Induced Apoptosis in Cancer Therapy

2020 ◽  
Vol 27 (13) ◽  
pp. 2118-2132 ◽  
Author(s):  
Aysegul Hanikoglu ◽  
Hakan Ozben ◽  
Ferhat Hanikoglu ◽  
Tomris Ozben
Keyword(s):  
Oxidative Stress ◽  
Drug Resistance ◽  
Side Effects ◽  
Cancer Therapy ◽  
Tumor Cells ◽  
Anticancer Drugs ◽  
Chemotherapeutic Agents ◽  
Oxidation Reactions ◽  
Hybrid Compounds ◽  
Induced Apoptosis

: Elevated Reactive Oxygen Species (ROS) generated by the conventional cancer therapies and the endogenous production of ROS have been observed in various types of cancers. In contrast to the harmful effects of oxidative stress in different pathologies other than cancer, ROS can speed anti-tumorigenic signaling and cause apoptosis of tumor cells via oxidative stress as demonstrated in several studies. The primary actions of antioxidants in cells are to provide a redox balance between reduction-oxidation reactions. Antioxidants in tumor cells can scavenge excess ROS, causing resistance to ROS induced apoptosis. Various chemotherapeutic drugs, in their clinical use, have evoked drug resistance and serious side effects. Consequently, drugs having single-targets are not able to provide an effective cancer therapy. Recently, developed hybrid anticancer drugs promise great therapeutic advantages due to their capacity to overcome the limitations encountered with conventional chemotherapeutic agents. Hybrid compounds have advantages in comparison to the single cancer drugs which have usually low solubility, adverse side effects, and drug resistance. This review addresses two important treatments strategies in cancer therapy: oxidative stress induced apoptosis and hybrid anticancer drugs.

Recent Advances on Therapeutic Peptides for Breast Cancer Treatment

2020 ◽  
Vol 21 ◽  
Author(s):  
Samad Beheshtirouy ◽  
Farhad Mirzaei ◽  
Shirin Eyvazi ◽  
Vahideh Tarhriz
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Breast Cancer Cells ◽  
Specific Binding ◽  
High Specificity ◽  
The Novel ◽  
Anti Cancer ◽  
Therapeutic Peptides ◽  
Low Toxicity

: Breast cancer is a heterogeneous malignancy which is the second cause of mortality among women in the world. Increasing the resistance to anti-cancer drugs in breast cancer cells persuades researchers to search the novel therapies approaches for the treatment of the malignancy. Among the novel methods, therapeutic peptides which target and disrupt tumor cells have been of great interest. Therapeutic peptides are short amino acids monomer chains with high specificity to bind and modulate a protein interaction of interest. Several advantages of peptides such as specific binding on tumor cells surface, low molecular weight and low toxicity on normal cells make the peptides as an appealing therapeutic agents against solid tumors, particularly breast cancer. Also, National Institutes of Health (NIH) describes therapeutic peptides as suitable candidate for the treatment of drug-resistant breast cancer. In this review, we attempt to review the different therapeutic peptides against breast cancer cells which can be used in treatment and diagnosis of the malignancy. Meanwhile, we presented an overview of peptide vaccines which have been developed for the treatment of breast cancer.

scholarly journals Melatonin as an Adjuvant to Antiangiogenic Cancer Treatments

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3263
Author(s):  
Alicia González ◽  
Carolina Alonso-González ◽  
Alicia González-González ◽  
Javier Menéndez-Menéndez ◽  
Samuel Cos ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Protective Effect ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Chemotherapeutic Agents ◽  
Inhibitory Effects ◽  
Anticancer Effect ◽  
Cancer Treatments ◽  
Melatonin Administration ◽  
Effects Of Radiation

Melatonin is a hormone with different functions, antitumor actions being one of the most studied. Among its antitumor mechanisms is its ability to inhibit angiogenesis. Melatonin shows antiangiogenic effects in several types of tumors. Combination of melatonin and chemotherapeutic agents have a synergistic effect inhibiting angiogenesis. One of the undesirable effects of chemotherapy is the induction of pro-angiogenic factors, whilst the addition of melatonin is able to overcome these undesirable effects. This protective effect of the pineal hormone against angiogenesis might be one of the mechanisms underlying its anticancer effect, explaining, at least in part, why melatonin administration increases the sensitivity of tumors to the inhibitory effects exerted by ordinary chemotherapeutic agents. Melatonin has the ability to turn cancer totally resistant to chemotherapeutic agents into a more sensitive chemotherapy state. Definitely, melatonin regulates the expression and/or activity of many factors involved in angiogenesis which levels are affected (either positively or negatively) by chemotherapeutic agents. In addition, the pineal hormone has been proposed as a radiosensitizer, increasing the oncostatic effects of radiation on tumor cells. This review serves as a synopsis of the interaction between melatonin and angiogenesis, and we will outline some antiangiogenic mechanisms through which melatonin sensitizes cancer cells to treatments, such as radiotherapy or chemotherapy.

In situ injection of dual-delivery PEG based MMP-2 sensitive hydrogels for enhanced tumor penetration and chemo-immune combination therapy

Nanoscale ◽  
2021 ◽  
Author(s):  
Jianqin Yan ◽  
Zhuangzhuang Zhang ◽  
xiaohui Zhan ◽  
Keqi Chen ◽  
Yuji Pu ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Cancer Treatment ◽  
Deep Penetration ◽  
Tumor Penetration ◽  
Dna Nanostructure ◽  
Promising Strategy

mproving the deep penetration of nanoparticles and realizing the combination of chemotherapy and immunotherapy have become a promising strategy for cancer treatment. Herein, nuclear-targeted tetrahedral DNA nanostructure (NLS-TDNs, NT) was...

scholarly journals Anthracycline-induced cytotoxicity in the GL261 glioma model system

2021 ◽  
Author(s):  
Amber M. Tavener ◽  
Megan C. Phelps ◽  
Richard L. Daniels
Keyword(s):  
Cell Viability ◽  
Tumor Cells ◽  
Flow Cytometric Analysis ◽  
Annexin V ◽  
Chemotherapeutic Agents ◽  
Cytotoxic Effects ◽  
High Concentrations ◽  
Induced Apoptosis ◽  
Dose Dependent ◽  
Gl261 Glioma

AbstractGlioblastoma (GBM) is a lethal astrocyte-derived tumor that is currently treated with a multi-modal approach of surgical resection, radiotherapy, and temozolomide-based chemotherapy. Alternatives to current therapies are urgently needed as its prognosis remains poor. Anthracyclines are a class of compounds that show great potential as GBM chemotherapeutic agents and are widely used to treat solid tumors outside the central nervous system. Here we investigate the cytotoxic effects of doxorubicin and other anthracyclines on GL261 glioma tumor cells in anticipation of novel anthracycline-based CNS therapies. Three methods were used to quantify dose-dependent effects of anthracyclines on adherent GL261 tumor cells, a murine cell-based model of GBM. MTT assays quantified anthracycline effects on cell viability, comet assays examined doxorubicin genotoxicity, and flow cytometry with Annexin V/PI staining characterized doxorubicin-induced apoptosis and necrosis. Dose-dependent reductions in GL261 cell viability were found in cells treated with doxorubicin (EC50 = 4.9 μM), epirubicin (EC50 = 5.9 μM), and idarubicin (EC50 = 4.4 μM). Comet assays showed DNA damage following doxorubicin treatments, peaking at concentrations of 1.0 μM and declining after 25 μM. Lastly, flow cytometric analysis of doxorubicin-treated cells showed dose-dependent induction of apoptosis (EC50 = 5.2 μM). Together, these results characterized the cytotoxic effects of anthracyclines on GL261 glioma cells. We found dose-dependent apoptotic induction; however at high concentrations we find that cell death is likely necrotic. Our results support the continued exploration of anthracyclines as compounds with significant potential for improved GBM treatments.

scholarly journals Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice

2008 ◽  
Author(s):  
Pierre Sonveaux ◽  
Frédérique Végran ◽  
Thies Schroeder ◽  
Melanie C. Wergin ◽  
Julien Verrax ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Hypoxic Tumor

A cyanine-derived “turn-on” fluorescent probe for imaging nitroreductase in hypoxic tumor cells

2015 ◽  
Vol 7 (24) ◽  
pp. 10125-10128 ◽  
Author(s):  
Cong Xue ◽  
Yingjie Lei ◽  
Sichun Zhang ◽  
Yaowu Sha
Keyword(s):  
Tumor Cells ◽  
Fluorescent Probe ◽  
Phenol Group ◽  
Turn On ◽  
Hypoxic Tumor

A new “turn-on” fluorescent probe, composed of a protected phenol group with ap-nitrobenzyl moiety that functions as a latent donor and conjugated with two benzo[f]indolinium acceptors, was developed and applied for imaging nitroreductase (NTR) in hypoxic tumor cells.

pH-responsive size-shrinkable mesoporous silica-based nanocarrier for improved tumor penetration and therapeutic efficacy

Nanoscale ◽  
2022 ◽  
Author(s):  
Yongju He ◽  
Xingyu Fan ◽  
Xiaozan Wu ◽  
Taishun Hu ◽  
Fangfang Zhou ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Mesoporous Silica ◽  
Therapeutic Efficacy ◽  
Anticancer Therapy ◽  
Major Obstacle ◽  
Drug Penetration ◽  
Ph Responsive ◽  
Tumor Penetration ◽  
Promising Strategy

Poor tumor penetration is a major obstacle to nanomedicine for achieving effective anticancer therapy. Tumor microenvironment-induced nanomedicine size shrinkage is a promising strategy to overcome the drug penetration barrier across...

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