Vascular and extracellular matrix remodeling by physical approaches to improve drug delivery at the tumor site

ABSTRACT

Introduction

Modern comprehensive studies of tumor microenvironment changes allowed scientists to develop new and more efficient strategies that will improve anticancer drug delivery on site. The tumor microenvironment, especially the dense extracellular matrix, has a recognized capability to hamper the penetration of conventional drugs. Development and co-applications of strategies aiming at remodeling the tumor microenvironment are highly demanded to improve drug delivery at the tumor site in a therapeutic prospect.

Areas covered

Increasing indications suggest that classical physical approaches such as exposure to ionizing radiations, hyperthermia or light irradiation, and emerging ones as sonoporation, electric field or cold plasma technology can be applied as standalone or associated strategies to remodel the tumor microenvironment. The impacts on vasculature and extracellular matrix remodeling of these physical approaches will be discussed with the goal to improve nanotherapeutics delivery at the tumor site.

Expert opinion

Physical approaches to modulate vascular properties and remodel the extracellular matrix are of particular interest to locally control and improve drug delivery and thus increase its therapeutic index. They are particularly powerful as adjuvant to nanomedicine delivery; the development of these technologies could have extremely widespread implications for cancer treatment.

KEYWORDS:

• Collagens
• ECM
• tumor microenvironment
• radiotherapy
• hyperthermia
• photodynamic therapy (PDT)
• electroporation
• sonoporation
• cold atmospheric plasma
• vascular permeability

Article highlights

• As opposed to pharmacological strategies, physical approaches allow a spatial and temporal treatment of the target tissue.

• Radiotherapy (RT), by damaging tumor vasculature and ECM, enhance nanotherapeutics drug delivery and subsequent increase of RT activity at the tumour site leading to significant reduction of both resistance processes and tumor hypoxia.

• Hyperthermia therapy, focused ultrasounds or alternative magnetic fields, are three approaches that prime the tumor by disrupting extracellular matrix and tumor vasculature, enhancing on-site drug delivery.

• Chemophototherapy, the combination of phototherapy and chemotherapy, is an efficient strategy to induce tumor vascular permeability and ensuing drug delivery to tumors.

• Standalone or co-applied physical strategies to disrupt the dense tumor extracellular matrix or to mediate vascular permeability may be of major interest to improve drug delivery at the tumor site in a therapeutic prospect.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

Lab2screen is acknowledged for English proofreading and editing as well as design creations for graphical abstract, Figures 2 and Figures 7.

Additional information

Funding

This work was supported by the French Agence Nationale de la recherche under Grant ANR-17-CE19-0013-01.