Designing Hypoxia‐Responsive Nanotheranostic Agents for Tumor Imaging and Therapy

Abstract

Hypoxia, a common feature of most solid tumors, plays an important role in tumor proliferation, metastasis, and invasion, leading to drug, radiation, and photodynamic therapy resistance, and resulting in a sharp reduction in the disease‐free survival rate of tumor patients. The lack of sufficient blood supply to the interior regions of tumors hinders the delivery of traditional drugs and contrast agents, interfering with their accumulation in the hypoxic region, and preventing efficient theranostics. Thus, there is a need for the fabrication of novel tumor theranostic agents that overcome these obstacles. Reports, in recent years, of hypoxia‐responsive nanomaterials may provide with such means. In this review, a comprehensive description of the physicochemical and biological characteristics of hypoxic tumor tissues is provided, the principles of designing the hypoxia‐responsive tumor theranostic agents are discussed, and the recent research into hypoxia‐triggered nanomaterials is examined. Additionally, other hypoxia‐associated responsive strategies, the current limitations, and future prospects for hypoxia‐responsive nanotheranostic agents in tumor treatment are discussed.

Oxygen nanocarrier broke the hypoxia trap of solid tumors and rescued transfection efficiency for gene therapy

“…Malignant cellular proliferation and aberrant neovascularization cause tumor hypoxia inevitably, which is a common characteristic in rapidly growing solid tumors [ 8 ]. Notably, the adaptation of progressing tumors to hypoxia not only accelerates tumor invasion and metastasis but inhibits T lymphocytes functions and antigen presentation capacity of dendritic cells (DCs), thereby strongly enhancing the immunosuppressive microenvironment and greatly reducing the efficacy of various treatments, including gene therapy [ 9 – 12 ].…”

A novel targeted multifunctional nanoplatform for visual chemo-hyperthermia synergy therapy on metastatic lymph nodes via lymphatic delivery

“…Oxygen plays a key substrate in cell metabolism, signal transduction and maintaining normal physiological functions, while hypoxia is the basic feature of the tumor microenvironment (TME) [ 41 – 43 ]. Hypoxia-inducible factor 1 (HIF 1) is an important transcription factor that regulates oxygen homeostasis [ 44 , 45 ] by inducing the expression of genes that mediate the adaptive response of cells to hypoxia [ 46 , 47 ].…”

Recent advances in peptide-based nanomaterials for targeting hypoxia

“…3 Hypoxia is related to the malignant degree, invasion, and prognosis of a tumor, as well as resistance to radiotherapy and chemotherapy, with higher degrees of hypoxia in tumors decreasing therapeutic response. 4,5 For some anticancer drugs, oxygen increases the cytotoxicity of cell damage they cause. Therefore, hypoxia has become the main target of cancer treatment in tumor progression as well as a significant challenge to overcome in the development of new therapies that do not result in resistance to treatment.…”

“…Fig 5. Molecular design of self-assembled CA IX inhibitors (A) and their hypoxic cancer cell-targeted self-assembly (B).…”