Anticancer nanomedicines harnessing tumor microenvironmental components

ABSTRACT

Introduction

Small-molecular drugs are extensively used in cancer therapy, while they have issues of nonspecific distribution and consequent side effects. Nanomedicines that incorporate chemotherapeutic drugs have been developed to enhance the therapeutic efficacy of these drugs and reduce their side effects. One of the promising strategies is to prepare nanomedicines by harnessing the unique tumor microenvironment (TME).

Areas covered

The TME contains numerous cell types that specifically express specific antibodies on the surface. The physicochemical environment is characterized with a low pH, hypoxia, and a high redox potential resulting from tumor-specific metabolism. Therefore, intelligent nanomedicines designed based on the characteristics of the tumor microenvironment can be divided into two groups: the first group which is rapidly responsive to extracellular chemical/biological factors in the TME and the second one which actively and/or specifically targets cellular components in the TME.

Expert opinion

In this paper, we review recent progress of nanomedicines by harnessing the TME and illustrate the principles and advantages of different strategies for designing nanomedicines, which are of great significance for exploring novel nanomedicines or translating current nanomedicines into clinical practice. We will discuss the challenges and prospects of preparing nanomedicines to utilize or alter the TME for achieving effective, safe anticancer treatment.

KEYWORDS:

• Nanomedicine
• stimuli-responsive drug delivery systems
• tumor microenvironment
• tumor immunosuppressive microenvironment

Article highlights

• The tumor microenvironment is a complex network containing a large number of different cell types, including tumor vascular endothelial cells, tumor-associated adipocytes, and tumor-associated fibroblasts.

• The tumor is characterized with a special physicochemical environment with a low pH, hypoxia and a high redox potential caused by tumor-specific metabolism.

• Targeting the tumor tissue can be achieved by specifically interacting its cellular components and harnessing its physical characteristics.

• The strategy of designing tumor-targeting nanomedicines by targeting its cellular components is to identify unique molecules expressed in the TME, while these molecules may be absent or present at a low level in normal tissues.

• TME-responsive nanomedicines are special to the tumor tissue by incorporating chemical bonds to their structures that are sensitive to extracellular chemical/biological factors in the TME. Under the action of extracellular chemical/biological factors in the TME, the chemical bond between the drug and the carrier is cleaved, thus realizing drug delivery to the target tumor cells.

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.

Additional information

Funding

This work was financially supported by National Natural Science Foundation of China (No. 52073193, No.51873120, No.81621003, No.81801820), 1‧3‧5 project for disciplines of excellence, West China Hospital, Sichuan University (No.ZYJC21013, No.ZYGD20007, No.ZYJC18011), Science and Technology Program of Sichuan province (No.2020YJ0231, No.2018JY0574) and Postdoctoral Science Foundation of China (No.2018M643493).