Cancer Brachytherapy at the Nanoscale: An Emerging Paradigm

Abstract

Brachytherapy is an established treatment modality that has been globally utilized for the therapy of malignant solid tumors. However, classic therapeutic sealed sources used in brachytherapy must be surgically implanted directly into the tumor site and removed after the requisite period of treatment. In order to avoid the trauma involved in the surgical procedures and prevent undesirable radioactive distribution at the cancerous site, welldispersed radiolabeled nanomaterials are now being explored for brachytherapy applications. This emerging field has been coined "nanoscale brachytherapy". Despite present-day advancements, an ongoing challenge is obtaining an advanced, functional nanomaterial that concurrently incorporates features of high radiolabeling yield, short labeling time, good radiolabeling stability, and long tumor retention time without leakage of radioactivity to the nontargeted organs. Further, attachment of suitable targeting ligands to the nanoplatforms would widen the nanoscale brachytherapy approach to tumors expressing various phenotypes. Molecular imaging using radiolabeled nanoplatforms enables noninvasive visualization of cellular functions and biological processes in vivo. In vivo imaging also aids in visualizing the localization and retention of the radiolabeled nanoplatforms at the tumor site for the requisite time period to render safe and effective therapy. Herein, we review the advancements over the last several years in the synthesis and use of functionalized radiolabeled nanoplatforms as a noninvasive substitute to standard brachytherapy sources. The limitations of present-day brachytherapy sealed sources are analyzed, while highlighting the advantages of using radiolabeled nanoparticles (NPs) for this purpose. The recent progress in the development of different radiolabeling methods, delivery techniques and nanoparticle internalization mechanisms are discussed. The preclinical studies performed to date are summarized with an emphasis on the current challenges toward the future translation of nanoscale brachytherapy in routine clinical practices.

Smart Molecular Imaging and Theranostic Probes by Enzymatic Molecular In Situ Self-Assembly

“…Theranostic probes, which combine imaging and therapy to allow imaging-guided therapy, are a promising tool for precision medicine. Considering that the E-MISA strategy could enhance the accumulation of various imaging moieties at the target tissues for in vivo imaging of different enzyme activities, the integration of therapeutic functions into the E-MISA strategy could be amenable to the design of enzyme-activable therapeutic probes for imaging-guided on-demand therapy. − Currently, a number of E-MISA theranostic probes have been reported by integrating different imaging modalities with different therapeutic modes, such as chemotherapy, phototherapy (e.g., photodynamic therapy (PDT) and photothermal therapy (PTT)), SDT and combination therapy.…”

177Lu-Labeled Iron Oxide Nanoparticles Functionalized with Doxorubicin and Bevacizumab as Nanobrachytherapy Agents against Breast Cancer

“…For example, breast brachytherapy has been studied as a supporting treatment as well as a standalone treatment when used in high doses [ 5 , 6 ]. While brachytherapy is a well-established method used in clinical practice, nanobrachytherapy or “nanoscale brachytherapy” is a relatively unexplored field with scarce studies over the last 15 years but with an exponentially increasing amount of interest in the last couple of years [ 7 ]. Nanobrachytherapy includes the use of nanoparticles (NPs) instead of seeds or devices (i.e., catheters) [ 8 ].…”