Nanobiohybrids: A Synergistic Integration of Bacteria and Nanomaterials in Cancer Therapy

Yuhao Chen; Meng Du; Jinsui Yu; Lang Rao; Xiaoyuan Chen; Zhiyi Chen

doi:10.15212/bioi-2020-0008

Nanobiohybrids: A Synergistic Integration of Bacteria and Nanomaterials in Cancer Therapy

BIO Integration ◽

10.15212/bioi-2020-0008 ◽

2020 ◽

Vol 1 (1) ◽

pp. 25-36

Author(s):

Yuhao Chen ◽

Meng Du ◽

Jinsui Yu ◽

Lang Rao ◽

Xiaoyuan Chen ◽

...

Keyword(s):

Cancer Therapy ◽

Cancer Treatment ◽

Targeted Delivery ◽

Tumor Targeting ◽

Tumor Tissue ◽

Tumor Therapy ◽

Fluid Pressure ◽

Therapeutic Agents ◽

Treatment Modalities ◽

Targeting Ability

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.

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Tumor-Targeting Peptides Search Strategy for the Delivery of Therapeutic and Diagnostic Molecules to Tumor Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22010314 ◽

2020 ◽

Vol 22 (1) ◽

pp. 314

Author(s):

Maria D. Dmitrieva ◽

Anna A. Voitova ◽

Maya A. Dymova ◽

Vladimir A. Richter ◽

Elena V. Kuligina

Keyword(s):

Phage Display ◽

Cell Sorting ◽

Targeted Delivery ◽

Tumor Targeting ◽

Search Strategy ◽

Tumor Therapy ◽

Therapeutic Agents ◽

Phage Libraries

Background: The combination of the unique properties of cancer cells makes it possible to find specific ligands that interact directly with the tumor, and to conduct targeted tumor therapy. Phage display is one of the most common methods for searching for specific ligands. Bacteriophages display peptides, and the peptides themselves can be used as targeting molecules for the delivery of diagnostic and therapeutic agents. Phage display can be performed both in vitro and in vivo. Moreover, it is possible to carry out the phage display on cells pre-enriched for a certain tumor marker, for example, CD44 and CD133. Methods: For this work we used several methods, such as phage display, sequencing, cell sorting, immunocytochemistry, phage titration. Results: We performed phage display using different screening systems (in vitro and in vivo), different phage libraries (Ph.D-7, Ph.D-12, Ph.D-C7C) on CD44+/CD133+ and without enrichment U-87 MG cells. The binding efficiency of bacteriophages displayed tumor-targeting peptides on U-87 MG cells was compared in vitro. We also conducted a comparative analysis in vivo of the specificity of the accumulation of selected bacteriophages in the tumor and in the control organs (liver, brain, kidney and lungs). Conclusions: The screening in vivo of linear phage peptide libraries for glioblastoma was the most effective strategy for obtaining tumor-targeting peptides providing targeted delivery of diagnostic and therapeutic agents to glioblastoma.

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Targeted Protein Liposomes-Mediated AChE Gene Therapy for Effective Liver Cancer Treatment

10.21203/rs.3.rs-45975/v2 ◽

2020 ◽

Author(s):

Kai Wang ◽

Fusheng Shang ◽

Dagui Chen ◽

Tieliu Cao ◽

Xiaowei Wang ◽

...

Keyword(s):

Gene Therapy ◽

Cancer Therapy ◽

Gene Delivery ◽

Liver Cancer ◽

Cancer Treatment ◽

Targeted Delivery ◽

Tumor Targeting ◽

Transfection Efficiency ◽

Subcutaneous Administration ◽

Viral Gene

Abstract Background: Effective methods to deliver therapeutic genes to solid tumors and improve their bioavailability are the main challenges of current medical research on gene therapy. The development of efficient non-viral gene vector with tumor-targeting has very important application value in the field of cancer therapy. Proteolipid integrated with tumor-targeting potential of functional protein and excellent gene delivery performance has shown potential for targeted gene therapy.Results: Herein, we prepared transferrin-modified liposomes (Tf-PL) for the targeted delivery of acetylcholinesterase (AChE) therapeutic gene to liver cancer. We found that the derived Tf-PL/AChE liposomes exhibited much higher transfection efficiency than the commercial product Lipo 2000 and shown premium targeting efficacy to liver cancer SMMC-7721 cells in vitro. In vivo, the Tf-PL/AChE could effectively target liver cancer, and significantly inhibit the growth of liver cancer xenografts grafted in nude mice by subcutaneous administration. Conclusion: This study proposed a transferrin-modified proteolipid-mediated gene delivery strategy for targeted liver cancer treatment, which has a promising potential for precise personalized cancer therapy.

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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

10.31219/osf.io/embqk ◽

2021 ◽

Author(s):

Moataz Dowaidar

Keyword(s):

Clinical Trials ◽

Cancer Therapy ◽

Cancer Treatment ◽

Negative Charge ◽

Human Cancer ◽

Drug Loading ◽

Tumor Therapy ◽

Preclinical Research ◽

Immunodeficient Mice ◽

Virulence Attenuation

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.

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A Low Dose of Hydrous Icaritin Nano-Formulation with Remarkable Efficacy and Tumor Targeting in Cancer Therapy

Journal of Biomedical Nanotechnology ◽

10.1166/jbn.2021.3176 ◽

2021 ◽

Vol 17 (10) ◽

pp. 2003-2013

Author(s):

Jingxin Fu ◽

Yian Wang ◽

Haowen Li ◽

Likang Lu ◽

Hui Ao ◽

...

Keyword(s):

Cancer Therapy ◽

Tumor Targeting ◽

Low Dose ◽

Drug Loading ◽

Tumor Therapy ◽

High Dose ◽

Inhibition Rate ◽

Tumor Inhibition ◽

Nano Formulation ◽

Tumor Inhibition Rate

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.

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Polymeric Co-Delivery Systems in Cancer Treatment: An Overview on Component Drugs’ Dosage Ratio Effect

Molecules ◽

10.3390/molecules24061035 ◽

2019 ◽

Vol 24 (6) ◽

pp. 1035 ◽

Cited By ~ 22

Author(s):

Jiayi Pan ◽

Kobra Rostamizadeh ◽

Nina Filipczak ◽

Vladimir Torchilin

Keyword(s):

Cancer Therapy ◽

Cancer Treatment ◽

Therapeutic Agent ◽

Polymeric Nanoparticles ◽

Therapeutic Agents ◽

Delivery Systems ◽

Individual Therapy ◽

Multiple Factors ◽

Therapeutic Outcomes ◽

Anti Cancer

Multiple factors are involved in the development of cancers and their effects on survival rate. Many are related to chemo-resistance of tumor cells. Thus, treatment with a single therapeutic agent is often inadequate for successful cancer therapy. Ideally, combination therapy inhibits tumor growth through multiple pathways by enhancing the performance of each individual therapy, often resulting in a synergistic effect. Polymeric nanoparticles prepared from block co-polymers have been a popular platform for co-delivery of combinations of drugs associated with the multiple functional compartments within such nanoparticles. Various polymeric nanoparticles have been applied to achieve enhanced therapeutic efficacy in cancer therapy. However, reported drug ratios used in such systems often vary widely. Thus, the same combination of drugs may result in very different therapeutic outcomes. In this review, we investigated polymeric co-delivery systems used in cancer treatment and the drug combinations used in these systems for synergistic anti-cancer effect. Development of polymeric co-delivery systems for a maximized therapeutic effect requires a deeper understanding of the optimal ratio among therapeutic agents and the natural heterogenicity of tumors.

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Hyaluronic acid-modified zirconium phosphate nanoparticles for potential lung cancer therapy

Biomedical Engineering / Biomedizinische Technik ◽

10.1515/bmt-2015-0238 ◽

2017 ◽

Vol 62 (1) ◽

Cited By ~ 3

Author(s):

Ranwei Li ◽

Tiecheng Liu ◽

Ke Wang

Keyword(s):

Lung Cancer ◽

Hyaluronic Acid ◽

Cancer Therapy ◽

Cancer Cells ◽

Tumor Targeting ◽

Zirconium Phosphate ◽

Drug Loading ◽

Lung Cancer Therapy ◽

Targeting Ability ◽

A549 Lung

AbstractNovel tumor-targeting zirconium phosphate (ZP) nanoparticles modified with hyaluronic acid (HA) were developed (HA-ZP), with the aim of combining the drug-loading property of ZP and the tumor-targeting ability of HA to construct a tumor-targeting paclitaxel (PTX) delivery system for potential lung cancer therapy. The experimental results indicated that PTX loading into the HA-ZP nanoparticles was as high as 20.36%±4.37%, which is favorable for cancer therapy. PTX-loaded HA-ZP nanoparticles increased the accumulation of PTX in A549 lung cancer cells via HA-mediated endocytosis and exhibited superior anticancer activity

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Subcellular co-delivery of two different site-oriented payloads based on multistage targeted polymeric nanoparticles for enhanced cancer therapy

Journal of Materials Chemistry B ◽

10.1039/c8tb02230e ◽

2018 ◽

Vol 6 (42) ◽

pp. 6752-6766 ◽

Cited By ~ 14

Author(s):

Chao-Qun You ◽

Hong-Shuai Wu ◽

Zhi-Guo Gao ◽

Kai Sun ◽

Fang-Hui Chen ◽

...

Keyword(s):

Cancer Therapy ◽

Targeted Delivery ◽

Polymeric Nanoparticles ◽

Therapeutic Agents ◽

Antitumor Therapy

Smart nanoparticles which encapsulated two different site-oriented therapeutic agents for multistage targeted delivery and enhanced antitumor therapy.

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Photosensitizer-Functionalized Nanocomposites for Light-Activated Cancer Theranostics

International Journal of Molecular Sciences ◽

10.3390/ijms22136658 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6658

Author(s):

Banendu Sunder Dash ◽

Suprava Das ◽

Jyh-Ping Chen

Keyword(s):

Cancer Therapy ◽

Cancer Treatment ◽

Penetration Depth ◽

Targeted Delivery ◽

Near Infrared ◽

Red Light ◽

Light Sources ◽

Combination Cancer Therapy ◽

Red Light Laser ◽

Cancer Theranostics

Photosensitizers (PSs) have received significant attention recently in cancer treatment due to its theranostic capability for imaging and phototherapy. These PSs are highly responsive to light source of a suitable wavelength for image-guided cancer therapy from generated singlet oxygen and/or thermal heat. Various organic dye PSs show tremendous attenuation of tumor cells during cancer treatment. Among them, porphyrin and chlorophyll-based ultraviolet-visible (UV-Vis) dyes are employed for photodynamic therapy (PDT) by reactive oxygen species (ROS) and free radicals generated with 400–700 nm laser lights, which have poor tissue penetration depth. To enhance the efficacy of PDT, other light sources such as red light laser and X-ray have been suggested; nonetheless, it is still a challenging task to improve the light penetration depth for deep tumor treatment. To overcome this deficiency, near infrared (NIR) (700–900 nm) PSs, indocyanine green (ICG), and its derivatives like IR780, IR806 and IR820, have been introduced for imaging and phototherapy. These NIR PSs have been used in various cancer treatment modality by combining photothermal therapy (PTT) and/or PDT with chemotherapy or immunotherapy. In this review, we will focus on the use of different PSs showing photothermal/photodynamic response to UV-Vis or NIR-Vis light. The emphasis is a comprehensive review of recent smart design of PS-loaded nanocomposites for targeted delivery of PSs in light-activated combination cancer therapy.

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Mitochondria-Targeted Nanocarriers Promote Highly Efficient Cancer Therapy: A Review

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.784602 ◽

2021 ◽

Vol 9 ◽

Author(s):

Zeng Zeng ◽

Chao Fang ◽

Ying Zhang ◽

Cong-Xian Chen ◽

Yi-Feng Zhang ◽

...

Keyword(s):

Cancer Therapy ◽

Cancer Treatment ◽

Therapeutic Agents ◽

Sonodynamic Therapy ◽

Therapeutic Modalities ◽

Normal Functions ◽

The Past ◽

Highly Efficient ◽

Apoptotic Pathways ◽

Mitochondria Targeting

Mitochondria are the primary organelles which can produce adenosine triphosphate (ATP). They play vital roles in maintaining normal functions. They also regulated apoptotic pathways of cancer cells. Given that, designing therapeutic agents that precisely target mitochondria is of great importance for cancer treatment. Nanocarriers can combine the mitochondria with other therapeutic modalities in cancer treatment, thus showing great potential to cancer therapy in the past few years. Herein, we summarized lipophilic cation- and peptide-based nanosystems for mitochondria targeting. This review described how mitochondria-targeted nanocarriers promoted highly efficient cancer treatment in photodynamic therapy (PDT), chemotherapy, combined immunotherapy, and sonodynamic therapy (SDT). We further discussed mitochondria-targeted nanocarriers’ major challenges and future prospects in clinical cancer treatment.

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