Preclinical investigations revealed possibilities for Salmonella tumor treatment. Bacteria can also be coupled to nanomaterials enabling drug-loading, photocatalytic and/or magnetic properties, using the bacteria's net negative charge

2021 ◽  
Author(s):  
Moataz Dowaidar

Except in human clinical trials, preclinical tests showed the potential of Salmonella bacteria for tumor therapy. There are still various challenges to tackle before salmonella bacteria may be employed to treat human cancer. Due to its pathogenic nature, attenuation is essential to minimize the host's harmful effects of bacterial infection. Loss of anticancer efficacy from bacterial virulence attenuation can be compensated by giving therapeutic payloads to microorganisms. Bacteria can also be linked to micro-or nanomaterials with diverse properties, such as drug-loaded, photocatalytic and/or magnetic-sensing nanoparticles, using the net negative charge of the bacteria. Combining bacteria-mediated cancer treatment with other medicines that have been clinically shown to be helpful but have limits may provide surprising therapeutic results. Recently, this strategy has received attention and is underway. The use of live germs for cancer treatment has not yet been approved for human clinical trials. The non-invasive oral form of administration benefits from safety, making it more suitable for clinical cancer patients.Infection of live germs through systemic means, on the other hand, involves toxicity risk. Although Salmonella bacteria can be genetically manipulated with high tumor targeting, harm to normal tissues can not be excluded when medications with nonspecific toxicity are administered. It is preferred if the action of selected drugs may be restricted to the tumor site rather than healthy tissues, thereby boosting cancer therapy safety. In recent years, many regulatory mechanisms have been developed to manage pharmaceutical distribution through live bacterial vectors. Engineered salmonella can accumulate 1000 times greater than normal tissue density in the tumor. The QS-regulated mechanism, which initiates gene expression when bacterial density exceeds a particular threshold level, also promises Salmonella bacteria for targeted medication delivery. Nanovesicle structures of Salmonella bacteria can also be used as biocompatible nanocarriers to deliver functional medicinal chemicals in cancer therapy. Surface-modified nanovesicles preferably attach to tumor cells and are swallowed by receptor-mediated endocytosis before being destroyed to release packed drugs. The xenograft methodology, which comprises the implantation of cultivated tumor cell lines into immunodeficient mice, has often been used in preclinical research revealing favorable results about the anticancer effects of genetically engineered salmonella.

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 520
Author(s):  
Tianqi Wang ◽  
Yusuke Suita ◽  
Saradha Miriyala ◽  
Jordan Dean ◽  
Nikos Tapinos ◽  
...  

Nanomedicines have shown great potential in cancer therapy; in particular, the combination of chemotherapy and immunotherapy (namely chemoimmunotherapy) that is revolutionizing cancer treatment. Currently, most nanomedicines for chemoimmunotherapy are still in preclinical and clinical trials. Lipid-based nanoparticles, the most widely used nanomedicine platform in cancer therapy, is a promising delivery platform for chemoimmunotherapy. In this review, we introduce the commonly used immunotherapy agents and discuss the opportunities for chemoimmunotherapy mediated by lipid-based nanoparticles. We summarize the clinical trials involving lipid-based nanoparticles for chemoimmunotherapy. We also highlight different chemoimmunotherapy strategies based on lipid-based nanoparticles such as liposomes, nanodiscs, and lipid-based hybrid nanoparticles in preclinical research. Finally, we discuss the challenges that have hindered the clinical translation of lipid-based nanoparticles for chemoimmunotherapy, and their future perspectives.


Author(s):  
Menghan Gao ◽  
Hong Deng ◽  
Weiqi Zhang

: Hyaluronan (HA) is a natural linear polysaccharide that has excellent hydrophilicity, biocompatibility, biodegradability, and low immunogenicity, making it one of the most attractive biopolymers used for biomedical researches and applications. Due to the multiple functional sites on HA and its intrinsic affinity for CD44, a receptor highly expressed on various cancer cells, HA has been widely engineered to construct different drug-loading nanoparticles (NPs) for CD44- targeted anti-tumor therapy. When a cocktail of drugs is co-loaded in HA NP, a multifunctional nano-carriers could be obtained, which features as a highly effective and self-targeting strategy to combat the cancers with CD44 overexpression. The HA-based multidrug nano-carriers can be a combination of different drugs, various therapeutic modalities, or the integration of therapy and diagnostics (theranostics). Up to now, there are many types of HA-based multidrug nano-carriers constructed by different formulation strategies including drug co-conjugates, micelles, nano-gels and hybrid NP of HA and so on. This multidrug nano-carrier takes the full advantages of HA as NP matrix, drug carriers and targeting ligand, representing a simplified and biocompatible platform to realize the targeted and synergistic combination therapy against the cancers. In this review, recent progresses about HA-based multidrug nano-carriers for combination cancer therapy are summarized and its potential challenges for translational applications have been discussed.


2021 ◽  
Vol 17 (10) ◽  
pp. 2003-2013
Author(s):  
Jingxin Fu ◽  
Yian Wang ◽  
Haowen Li ◽  
Likang Lu ◽  
Hui Ao ◽  
...  

Background: The use of chemotherapeutic drugs is restricted in the tumor-therapy because of the severely toxic and side effects among most important factors. The active herbal extracts are always used as a high dose while in the tumortherapy to achieve good anti-tumor effects. Hydrous icaritin has a high activity while there are few existing dosage forms as a result of low solubility in water and poor bioavailability. Results: The prepared hydrous icaritin nanorods (DP-HICT NRs) using mPEG2000-DSPE as a stabilizer, presented a narrow distribution of particle size with of 217 nm and a properly high drug-loading content of approximately 65.3±1.5%. A low dose of hydrous icaritin nano-formulation shows remarkable efficacy in cancer therapy (tumor inhibition rate: 61.36±10.80%) compared with the same dose of Paclitaxel injection (tumor inhibition rate: 66.80±4.43%), which approved as medicaments. Not only that, DP-HICT NRs can escape the clearance of the immune system and enhance targeting ability to the tumor site with only one excipient and such a low dose. Conclusions: This kind of nanoparticles contain a low dose of HICT used mPEG2000-DSPE as a stabilizer, while can achieve good tumor targeting as some active targeting agents and an anti-tumor effect as the PTX injection. There are broad prospects in drug safety, anti-tumor efficacy and even prognosis.


2005 ◽  
Vol 2 (1) ◽  
pp. 49-57 ◽  
Author(s):  
Richard J. Pietras ◽  
Olga K. Weinberg

Despite advances in the early detection of tumors and in the use of chemotherapy, radiotherapy and surgery for disease management, the worldwide mortality from human cancer remains unacceptably high. The treatment of cancer may benefit from the introduction of novel therapies derived from natural products. Natural products have served to provide a basis for many of the pharmaceutical agents in current use in cancer therapy. Emerging research indicates that progressive growth and spread of many solid tumors depends, in part, on the formation of an adequate blood supply, and this process of tumor-associated angiogenesis is reported to have prognostic significance in several human cancers. This review focuses on the potential application in antitumor therapy of naturally-occurring steroids that target tumor-associated angiogenesis. Squalamine, a 7,24 dihydroxylated 24-sulfated cholestane steroid conjugated to a spermidine at position C-3, is known to have strong antiangiogenic activityin vitro, and it significantly disrupts tumor proliferation and progression in laboratory studies. Work on the interactions of squalamine with vascular endothelial cells indicate that it binds with cell membranes, inhibits the membrane Na+/H+ exchanger and may further function as a calmodulin chaperone. These primary actions appear to promote inhibition of several vital steps in angiogenesis, such as blockade of mitogen-induced actin polymerization, cell–cell adhesion and cell migration, leading to suppression of endothelial cell proliferation. Preclinical studies with squalamine have shown additive benefits in tumor growth delay when squalamine is combined with cisplatin, paclitaxel, cyclophosphamide, genistein or radiation therapy. This compound has also been assessed in early phase clinical trials in cancer; squalamine was found to exhibit little systemic toxicity and was generally well tolerated by treated patients with various solid tumor malignancies, including ovarian, non-small cell lung and breast cancers. Clinical trials with squalamine alone or combined with standard chemotherapies or other biologic therapies, including antiangiogenic agents, should be considered for selected cancer patients, and further study of the mechanism of action and bioactivity of squalamine is warranted.


2020 ◽  
Vol 10 (19) ◽  
pp. 6898
Author(s):  
Lars Boeckmann ◽  
Mirijam Schäfer ◽  
Thoralf Bernhardt ◽  
Marie Luise Semmler ◽  
Ole Jung ◽  
...  

Plasma medicine is gaining increasing attention and is moving from basic research into clinical practice. While areas of application are diverse, much research has been conducted assessing the use of cold atmospheric pressure plasma (CAP) in wound healing and cancer treatment—two applications with entirely different goals. In wound healing, a tissue-stimulating effect is intended, whereas cancer therapy aims at killing malignant cells. In this review, we provide an overview of the latest clinical and some preclinical research on the efficacy of CAP in wound healing and cancer therapy. Furthermore, we discuss the current understanding of molecular signaling mechanisms triggered by CAP that grant CAP its antiseptic and tissue regenerating or anti-proliferative and cell death-inducing properties. For the efficacy of CAP in wound healing, already substantial evidence from clinical studies is available, while evidence for therapeutic effects of CAP in oncology is mainly from in vitro and in vivo animal studies. Efforts to elucidate the mode of action of CAP suggest that different components, such as ultraviolet (UV) radiation, electromagnetic fields, and reactive species, may act synergistically, with reactive species being regarded as the major effector by modulating complex and concentration-dependent redox signaling pathways.


Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3638
Author(s):  
Moon Jong Kim ◽  
Yuanjian Huang ◽  
Jae-Il Park

Wnt signaling governs tissue development, homeostasis, and regeneration. However, aberrant activation of Wnt promotes tumorigenesis. Despite the ongoing efforts to manipulate Wnt signaling, therapeutic targeting of Wnt signaling remains challenging. In this review, we provide an overview of current clinical trials to target Wnt signaling, with a major focus on gastrointestinal cancers. In addition, we discuss the caveats and alternative strategies for therapeutically targeting Wnt signaling for cancer treatment.


2016 ◽  
Vol 23 (4) ◽  
pp. 750-757 ◽  
Author(s):  
Jun Xu ◽  
Hee-Jin Lee ◽  
Jia Zeng ◽  
Yonghui Wu ◽  
Yaoyun Zhang ◽  
...  

Abstract Objective: Clinical trials investigating drugs that target specific genetic alterations in tumors are important for promoting personalized cancer therapy. The goal of this project is to create a knowledge base of cancer treatment trials with annotations about genetic alterations from ClinicalTrials.gov. Methods: We developed a semi-automatic framework that combines advanced text-processing techniques with manual review to curate genetic alteration information in cancer trials. The framework consists of a document classification system to identify cancer treatment trials from ClinicalTrials.gov and an information extraction system to extract gene and alteration pairs from the Title and Eligibility Criteria sections of clinical trials. By applying the framework to trials at ClinicalTrials.gov, we created a knowledge base of cancer treatment trials with genetic alteration annotations. We then evaluated each component of the framework against manually reviewed sets of clinical trials and generated descriptive statistics of the knowledge base. Results and Discussion: The automated cancer treatment trial identification system achieved a high precision of 0.9944. Together with the manual review process, it identified 20 193 cancer treatment trials from ClinicalTrials.gov. The automated gene-alteration extraction system achieved a precision of 0.8300 and a recall of 0.6803. After validation by manual review, we generated a knowledge base of 2024 cancer trials that are labeled with specific genetic alteration information. Analysis of the knowledge base revealed the trend of increased use of targeted therapy for cancer, as well as top frequent gene-alteration pairs of interest. We expect this knowledge base to be a valuable resource for physicians and patients who are seeking information about personalized cancer therapy.


Plasma ◽  
2018 ◽  
Vol 1 (1) ◽  
pp. 150-155 ◽  
Author(s):  
Hiromasa Tanaka ◽  
Masaaki Mizuno ◽  
Kenji Ishikawa ◽  
Shinya Toyokuni ◽  
Hiroaki Kajiyama ◽  
...  

Non-thermal plasma represents a novel approach in cancer treatment. Both direct and indirect plasma treatments are available, with clinical trials of direct plasma treatment in progress. Indirect treatments involve chemotherapy (i.e., plasma-activated medium) and immunotherapy. Recent studies suggest that integrated plasma treatments could be an extremely effective approach to cancer therapy.


2020 ◽  
Vol 1 (1) ◽  
pp. 25-36
Author(s):  
Yuhao Chen ◽  
Meng Du ◽  
Jinsui Yu ◽  
Lang Rao ◽  
Xiaoyuan Chen ◽  
...  

Abstract Cancer is a common cause of mortality in the world. For cancer treatment modalities such as chemotherapy, photothermal therapy and immunotherapy, the concentration of therapeutic agents in tumor tissue is the key factor which determines therapeutic efficiency. In view of this, developing targeted drug delivery systems are of great significance in selectively delivering drugs to tumor regions. Various types of nanomaterials have been widely used as drug carriers. However, the low tumor-targeting ability of nanomaterials limits their clinical application. It is difficult for nanomaterials to penetrate the tumor tissue through passive diffusion due to the elevated tumoral interstitial fluid pressure. As a biological carrier, bacteria can specifically colonize and proliferate inside tumors and inhibit tumor growth, making it an ideal candidate as delivery vehicles. In addition, synthetic biology techniques have been applied to enable bacteria to controllably express various functional proteins and achieve targeted delivery of therapeutic agents. Nanobiohybrids constructed by the combination of bacteria and nanomaterials have an abundance of advantages, including tumor targeting ability, genetic modifiability, programmed product synthesis, and multimodal therapy. Nowadays, many different types of bacteria-based nanobiohybrids have been used in multiple targeted tumor therapies. In this review, firstly we summarized the development of nanomaterial-mediated cancer therapy. The mechanism and advantages of the bacteria in tumor therapy are described. Especially, we will focus on introducing different therapeutic strategies of nanobiohybrid systems which combine bacteria with nanomaterials in cancer therapy. It is demonstrated that the bacteria-based nanobiohybrids have the potential to provide a targeted and effective approach for cancer treatment.


2018 ◽  
Vol 19 (10) ◽  
pp. 2963 ◽  
Author(s):  
Ying Wang ◽  
Pengfei Yang ◽  
Xinrui Zhao ◽  
Di Gao ◽  
Na Sun ◽  
...  

Nanocarriers encapsulating multiple chemotherapeutics are a promising strategy to achieve combinational chemotherapy for cancer therapy; however, they generally use exotic new carriers without therapeutic effect, which usually suffer from carrier-related toxicity issues, as well as having to pass extensive clinical trials to be drug excipients before any clinical applications. Cargo-free nanomedicines, which are fabricated by drugs themselves without new excipients and possess nanoscale characteristics to realize favorable pharmacokinetics and intracellular delivery, have been rapidly developed and drawn much attention to cancer treatment. Herein, we discuss recent advances of cargo-free nanomedicines for cancer treatment. After a brief introduction to the major types of carrier-free nanomedicine, some representative applications of these cargo-free nanomedicines are discussed, including combination therapy, immunotherapy, as well as self-monitoring of drug release. More importantly, this review draws a brief conclusion and discusses the future challenges of cargo-free nanomedicines from our perspective.


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