Exploiting a New Approach to Destroy the Barrier of Tumor Microenvironment: Nano-Architecture Delivery Systems

Abstract

Recent findings suggest that tumor microenvironment (TME) plays an important regulatory role in the occurrence, proliferation, and metastasis of tumors. Different from normal tissue, the condition around tumor significantly altered, including immune infiltration, compact extracellular matrix, new vasculatures, abundant enzyme, acidic pH value, and hypoxia. Increasingly, researchers focused on targeting TME to prevent tumor development and metastasis. With the development of nanotechnology and the deep research on the tumor environment, stimulation-responsive intelligent nanostructures designed based on TME have attracted much attention in the anti-tumor drug delivery system. TME-targeted nano therapeutics can regulate the distribution of drugs in the body, specifically increase the concentration of drugs in the tumor site, so as to enhance the efficacy and reduce adverse reactions, can utilize particular conditions of TME to improve the effect of tumor therapy. This paper summarizes the major components and characteristics of TME, discusses the principles and strategies of relevant nano-architectures targeting TME for the treatment and diagnosis systematically.

A tumor microenvironment-responsive poly(amidoamine) dendrimer nanoplatform for hypoxia-responsive chemo/chemodynamic therapy

“…Tumor microenvironment (TME) is characterized by weak acidity, high concentration of hydrogen peroxide (H 2 O 2 ), excessive glutathione (GSH), and hypoxia [ 1 – 3 ]. It has been well proved that TME not only plays an important role in the occurrence, development and metastasis of tumors [ 4 , 5 ], but also induces resistance to conventional anticancer treatments such as radiotherapy and chemotherapy, resulting in poor prognosis [ 5 , 6 ]. Nevertheless, TME could also be exploited to realize certain specific cancer treatments owing to its notable difference to normal tissues [ 7 ].…”

“…Nevertheless, TME could also be exploited to realize certain specific cancer treatments owing to its notable difference to normal tissues [ 7 ]. In addition, normalization of TME may in turn improve tumor therapy outcome [ 4 ]. Thereby a large number of TME-responsive cancer treatment strategies have been developed in recent years [ 8 – 10 ], including chemodynamic therapy (CDT) [ 11 – 13 ] and hypoxic-sensitive chemotherapy [ 14 , 15 ].…”

Advances in Graphene Platforms for Drug Delivery in Cancer and Its Biocompatibility

“…There may be low levels of glucose and other nutrients, as well as changes in temperature, all associated with various alterations in tumor cell metabolism [60]. While the heterogeneity of the tumor microenvironment sometimes makes it difficult to adequately characterize tumors [61], this has spawned interest in developing new nanotechnology therapeutic strategies to improve not only drug delivery conditions and directly destroy tumor cells, but also alter the balance between neoplastic cells and their microenvironment. Therefore, intelligent systems have been developed for the administration of drugs that respond to stimuli, and therapeutic agents can be activated by endogenous or exogenous stimuli [62,63].…”

Reactive Oxygen Species and Folate Receptor-Targeted Nanophotosensitizers Composed of Folic Acid-Conjugated and Poly(ethylene glycol)-Chlorin e6 Tetramer Having Diselenide Linkages for Targeted Photodynamic Treatment of Cancer Cells

“…For example, Lei et al reported that polymeric micelles having pH and temperature dual-responsive properties accelerate the release rate of anticancer drugs at an acidic pH and a higher temperature [ 20 ]. From these points of view, stimuli-responsive nanocarriers have great potential in tumor targeting, because the physiological properties of the tumor microenvironment are quite different from their normal counterparts (i.e., tumor tissues are characterized as having an acidic pH, abnormal redox status, abundant extra- or intra-cellular enzymes and elevated expression of various molecular receptors) [ 22 , 23 , 24 , 25 ]. Therefore, the abnormal status of a tumor microenvironment provides a tumor targeting opportunity for polymeric nanocarrier-based drug delivery [ 26 ].…”