Bacterial proteolytic activity improves drug delivery in tumors in a size, pharmacokinetic, and binding affinity dependent manner – A mechanistic understanding

Shirai, Hiroaki; Tsukada, Kosuke

doi:10.1016/j.jconrel.2020.02.024

Cited by 9 publications

(5 citation statements)

References 51 publications

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“…Motile bacteria are promising anticancer drug delivery vectors by virtue of their proteolytic activity toward ECM components that promote solid tumor colonization [51,52]. Recently, the engineering of bacteria to promote ECM degradation has been proposed as an innovative strategy to modify the immune landscape of the TME.…”

Section: Collagen-degrading Bacteriamentioning

confidence: 99%

Strategies for Efficient Targeting of Tumor Collagen for Cancer Therapy

Baldari¹,

Modugno²,

Nisticò³

et al. 2022

Cancers

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The tumor stroma, which comprises stromal cells and non-cellular elements, is a critical component of the tumor microenvironment (TME). The dynamic interactions between the tumor cells and the stroma may promote tumor progression and metastasis and dictate resistance to established cancer therapies. Therefore, novel antitumor approaches should combine anticancer and anti-stroma strategies targeting dysregulated tumor extracellular matrix (ECM). ECM remodeling is a hallmark of solid tumors, leading to extensive biochemical and biomechanical changes, affecting cell signaling and tumor tissue three-dimensional architecture. Increased deposition of fibrillar collagen is the most distinctive alteration of the tumor ECM. Consequently, several anticancer therapeutic strategies have been developed to reduce excessive tumor collagen deposition. Herein, we provide an overview of the current advances and challenges of the main approaches aiming at tumor collagen normalization, which include targeted anticancer drug delivery, promotion of degradation, modulation of structure and biosynthesis of collagen, and targeting cancer-associated fibroblasts, which are the major extracellular matrix producers.

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Section: Collagen-degrading Bacteriamentioning

confidence: 99%

Strategies for Efficient Targeting of Tumor Collagen for Cancer Therapy

Baldari¹,

Modugno²,

Nisticò³

et al. 2022

Cancers

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“…Regarding other factors contributing to the improvement of i DPSs, bacterial proteolytic activity [ 86 ] might be able to widen the localization area of bacteria, thus also being effective to spread anti-cancer substances produced by bacterial micro-factories to the whole tumor region from the central necrosis and/or periphery of the necrotic region where the anaerobic bacteria are colonized. For better distribution of anti-cancer substances in tumor tissue, there may be other ways to conjugate anti-tumor substances with oligopeptides to penetrate tumor masses and consequently widen the diffusion area of therapeutic agents [ 87 ].…”

Section: For Further Improvement Of the I Dpsmentioning

confidence: 99%

In Situ Delivery and Production System (iDPS) of Anti-Cancer Molecules with Gene-Engineered Bifidobacterium

Taniguchi

2021

JPM

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To selectively and continuously produce anti-cancer molecules specifically in malignant tumors, we have established an in situ delivery and production system (iDPS) with Bifidobacterium as a micro-factory of various anti-cancer agents. By focusing on the characteristic hypoxia in cancer tissue for a tumor-specific target, we employed a gene-engineered obligate anaerobic and non-pathogenic bacterium, Bifidobacterium, as a tool for systemic drug administration. This review presents and discusses the anti-tumor effects and safety of the iDPS production of numerous anti-cancer molecules and addresses the problems to be improved by directing attention mainly to the hallmark vasculature and so-called enhanced permeability and retention effect of tumors.

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“…These organisms could therefore serve as appropriate therapeutic payloads for tumor treatment. 19 However, the potential risk of infection remains a major concern on live bacteria-based therapy, especially when administered systemically. 20 How the live bacteria can be further manipulated to be safe and versatile at producing various therapeutic proteins awaits further investigation.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, anaerobic bacteria contribute to the restriction of tumor growth and can also compete with tumor cells in consuming nutrients, accompanied by secretion of proteins, toxins and other stimuli activating the immune system locally. These organisms could therefore serve as appropriate therapeutic payloads for tumor treatment 19 . However, the potential risk of infection remains a major concern on live bacteria‐based therapy, especially when administered systemically 20 .…”

Section: Introductionmentioning

confidence: 99%

Engineered oncolytic bacteria for malignant solid tumor treatment

Wang,

Song,

Liu

et al. 2024

Interdisciplinary Medicine

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Bacteria have been explored for their potential in fighting against cancer for decades. Due to their outstanding tumor‐targeting capacity and high biocompatibility, live bacteria can serve as microrobots delivering and producing anti‐tumor agents. In addition, live bacteria have intrinsic immune‐activating functions that aid in the generation of anti‐tumor immunity both systemically and locally in the tumor microenvironment. While bacteria‐based cancer therapy is still facing great challenges, progress in this platform combined with nanobiotechnologies has shown promise in terms of safety and effectiveness. Here, basic development strategies of bacteria‐based delivery systems armed with nanotechnologies, virulence attenuation, and genetic manipulation are summarized and the design of a spatiotemporal selectivity is particularly emphasized. In conclusion, the engineered bacteria platform has a high potentiality in the development of novel cancer therapeutics and holds prospects for future investigation and clinical use.

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Bacterial proteolytic activity improves drug delivery in tumors in a size, pharmacokinetic, and binding affinity dependent manner – A mechanistic understanding

Cited by 9 publications

References 51 publications

Strategies for Efficient Targeting of Tumor Collagen for Cancer Therapy

Strategies for Efficient Targeting of Tumor Collagen for Cancer Therapy

In Situ Delivery and Production System (iDPS) of Anti-Cancer Molecules with Gene-Engineered Bifidobacterium

Engineered oncolytic bacteria for malignant solid tumor treatment

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