Recent Advance in Tumor Microenvironment-Based Stimuli-Responsive Nanoscale Drug Delivery and Imaging Platform

Abstract

The tumor microenvironment (TME) plays an important role in the development, progression, and metastasis of cancer, and the extremely crucial feature is hypoxic and acidic. Cancer-associated fibroblasts (CAFs), extracellular matrix (ECM), mesenchymal cells, blood vessels, and interstitial fluid are widely recognized as fundamentally crucial hallmarks for TME. As nanotechnology briskly boomed, the nanoscale drug delivery and imaging platform (NDDIP) emerged and has attracted intensive attention. Based on main characteristics of TME, NDDIP can be classified into pH-sensitive delivery and imaging platforms, enzyme-sensitive delivery and imaging platforms, thermo-sensitive delivery and imaging platforms, redox-sensitive delivery and imaging platforms, and light-sensitive delivery and imaging platforms. Furthermore, imageology is one of the significant procedures for disease detection, image-guided drug delivery, and efficacy assessment, including magnetic resonance imaging (MRI), computed tomography (CT), ultrasound (US), and fluorescence imaging. Therefore, the stimuli-responsive NDDIP will be a versatile and practicable tumor disease diagnostic procedure and efficacy evaluation tool. In this review article, we mainly introduce the characteristics of TME and summarize the progress of multitudinous NDDIP as well as their applications.

Keywords: TME; cancer therapy; imaging platform; nanomaterials; stimuli-responsive nanoscale drug delivery.

FIGURE 1

Graphical summarization of five different types of stimuli put into the design of stimuli-sensitive nanocarriers for drug delivery and imaging platforms: pH-sensitive delivery and imaging platforms, enzyme-sensitive delivery and imaging platforms, thermo-sensitive delivery and imaging platforms, redox-sensitive delivery and imaging platforms, and light-sensitive delivery and imaging platforms.

FIGURE 2

| Malignant tumor cells are characterized by intracellular high concentrations of GSH. Advantage is taken from this in developing the redox-responsive drug delivery platform. Sun and colleagues explore redox-sensitive delivery platform (mPEG-ss-Tripp). Synthesized mPEG-ss-Tripp was loaded with doxorubicin via a disulfide bond, which is sensitive to reductive substance GSH and then quickly cleaved through thiol-disulfide exchange, in order to release the DOX at targeted sites without damaging normal tissues (Sun et al., 2021).