Harnessing Tumor Microenvironment for Nanoparticle‐Mediated Radiotherapy

Abstract

Recent years have witnessed the dramatic improvement of nanoparticle‐mediated radiotherapy in preclinical or even clinical cancer research. Among the extensive developments, tumor‐targeted strategies are receiving more and more attention as they become able increase their therapeutic effects as well as reduce the side effects to healthy tissues. The tumor microenvironment (TME) with its critical function in tumor development and distinctive abnormal characteristics, is also widely studied as a target/response for tumor‐specific nano‐radiotherapy. The fast advances of TME‐assisted nano‐radiotherapy have offered numerous novel strategies and approaches for efficiently destroying cancer. This review summarizes the recent advances and development of TME‐enabled nanoparticle‐mediated radiotherapy. Firstly, a brief description of the typical TME characteristics including vasculature, hypoxia, mild acidity, redox reactions, extracellular matrix, and various cellular components is given. Next, the representative examples of TME‐enabled nanoparticle‐mediated radiotherapy are categorized and discussed in two parts: TME components–targeted nano‐radiotherapy and TME characteristics‐responsive nano‐radiotherapy. Lastly, some obstacles and challenges associated with this field are also proposed at the end of this review.

Prostate-specific membrane antigen targeted gold nanoparticles for prostate cancer radiotherapy: does size matter for targeted particles?

“…Second, it appears that the location of the targeted-AuNP may impact the radiosensitizing efficacy. As evidenced by silver staining, the 2 nm AuNPs had a more homogeneous distribution and deeper penetration into cells and tumors than the 19 nm AuNPs, which may enable severe mitochondrial dysfunction and cellular damage induced by intracellular reactive oxygen species (ROS) upon radiation 9. Recently, Yang et al have shown that AuNPs delivered intracellularly via amphiphilic lipids are localized more homogeneously resulting in much higher radiation-induced cell killing 52.…”

“…Upon X-ray irradiation, gold has a greater absorptivity over soft tissue and generates secondary electrons, producing biological damage, e.g. DNA strand break and mitochondrial dysfunction, to cells and tissue 9,10. This makes AuNPs outstanding for enhancement of radiation therapy.…”

Targeted Gold Nanocluster‐Enhanced Radiotherapy of Prostate Cancer

“…In this case, radiation therapy is often necessary to reduce surgery‐related morbidities. More than half of the patients receive radiation in the form of electrons, protons, or photons (gamma‐ or X‐rays) during their battle against cancers . However, in the practice of radiation treatment, normal tissue is also exposed and potential radiotoxicity is, thus, unavoidable.…”

“…Upon X‐ray radiation, such radiosensitizers can generate secondary effects in the form of scattered photons, electrons, electron–positron pairs, or fluorescence. The secondary electrons can compromise and kill the cancer cells . The radiation enhancement is especially outstanding for gold (Z = 79).…”

Nano-Therapies for Glioblastoma Treatment

“…Indeed, TME is not only characterized by the presence of angiogenesis, but also by hypoxia, mild acidity, specific redox reactions, high interstitial pressure and dense stromal structure. When a nanoparticle based anti-GBM therapeutic approach is considered, such properties should be fully taken into consideration, in particular for reaching a homogenous NP distribution, which can be strongly affected by TME properties [96,116,117]. Methods to control nanoparticle distribution/activity within TME should be developed to achieve efficient anti-GBM treatment with nano-drugs.…”