Nanoscale Radiotheranostics for Cancer Treatment: From Bench to Bedside

Abstract

In recent years, the application of radionuclides-containing nanomaterials in cancer treatment has garnered widespread attention. The diversity of nanomaterials allows researchers to selectively combine them with appropriate radionuclides for biomedical purposes, addressing challenges faced by peptides, small molecules, or antibodies used for radionuclide labeling. However, with advantages come challenges, and nanoradionuclides still encounter significant issues during clinical translation. This review summarized the recent progress of nanosized radionuclides for cancer treatment or diagnosis. The discussion began with representative radionuclides and the methods of incorporating them into nanomaterial structures. Subsequently, new combinations of nanomaterials and radionuclides, along with their applications, were introduced to demonstrate their future trends. The benefits of nanoradionuclides included optimized pharmacokinetic properties, enhanced disease-targeting efficacy, and synergistic application with other treatment techniques. Besides, the basic rule of this section was to summarize how these nanoradionuclides can truly impact the diagnosis and therapy of various cancer types. In the last part, the focus was devoted to the nanoradionuclides currently applicable in clinics and how to address the existing issues and problems based on our knowledge.

Keywords: cancer therapy; nanoradionuclides; nuclear imaging; radiolabeling method; theranostics.

FIGURE 1

The main emission types from radionuclides and their penetration ranges. Therapeutic radionuclides emit α or β⁻ particles, or Auger electrons, while β⁺ and γ emitters were applicable for in vivo imaging (Banerjee, Pillai, and Knapp ; Chatal and Hoefnagel ; Kassis 2008).

FIGURE 2

(a) The illustration of ²²⁵Ac decay via a cascade of six radionuclides to stable ²⁰⁹Bi. Reproduced with permission from Cakici and Kilbas (2022); (b) Schematic representation of the treatment of U87MG using Au NPs labeled with ²²⁵Ac through DOTA. Reproduced with permission from Salvanou et al. (2020); (c) Polymersomes encapsulate ²¹³Bi through self‐assembly, leading to DNA damage in U2OS cells. Reproduced with permission from Roobol et al. (2020). (d) Specific binding of [²²³Ra]BaFe–CEPA–trastuzumab in SKOV‐3 (HER2⁺) and MDA‐MB‐231 (HER2⁻) cells. Reproduced with permission from Gawęda et al. (2020).

FIGURE 3

(a) The schematic diagram and action mechanism of radioimmunotherapy promoters‐augmented synergistic TAT/CDT/ICB therapy (²¹¹At‐ATE‐MnO₂‐BSA). (b) Biodistribution of free ²¹¹At, ²¹¹At‐ATE‐MnO₂‐BSA in 4 T1. (c) Statistical data depicting the maturation of dendritic cells induced by ²¹¹At‐ATE‐MnO₂‐BSA in mice with CT26 tumors. Note, 1: Control, 2: MnO₂‐BSA, 3: Free ²¹¹At, 4: ²¹¹At‐ATE‐MnO₂‐BSA. (d) A schematic illustration outlining the combination therapy aimed at generating anticancer immune memory and inhibiting cancer recurrence. (e) Tumor growth curves following various treatment regimens for rechallenged tumors. Reprinted with permission under a Creative Commons CC BY License from Zhang, Li, et al. (2022).

FIGURE 4

(a) A schematic diagram illustrating the construction of radioactive organic semiconducting polymer nanoparticles (rSPNs) for multimodal cancer theranostics by labeling poly (ethylene glycol) (PEG) grafted SPNs with ¹³¹I. Adapted with permission from Yu et al. (2022), Copyright 2022 Elsevier. (b) A schematic illustrating the proposed mechanism for enhanced ¹⁸⁸Re‐induced cancer cell killing by WS₂‐PEG, along with the relative viabilities of 4T1 cells pretreated with varying concentrations of ¹⁸⁸Re‐WS₂‐PEG labeled for 24 h. (c) SPECT images of 4T1 tumor‐bearing mice after i.v. injection with ¹⁸⁸Re‐WS₂‐PEG. Adapted with permission from Chao et al. (2016), Copyright 2016 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. (d) A schematic diagram of a dual receptor‐targeted radiation nanomedicine labeled with ¹⁷⁷Lu (DRT‐Au NPs‐¹⁷⁷Lu) for treating human breast cancer (BC) cells co‐expressing HER2 and EGFR. Adapted with permission from Yook et al. (2020), Copyright 2020 American Chemical Society.

FIGURE 5

(a) A schematic diagram depicting the alloying strategy and mechanisms for detoxification and theranostic multi‐functionalization in TeSe_x. (b) In vivo PET imaging of a 4T1 tumor‐bearing mouse captured at various time points following the injection of ⁶⁴Cu‐labeled TeSe_x nano‐alloys. Reproduced with permission from Ling et al. (2021) Copyright 2020 Oxford University Press. (c) A schematic diagram of ^68/67Ga‐radiolabeled sphingolipid nanoemulsions by PET and SPECT imaging. Reproduced with permission from Díez‐Villares et al. (2021) Copyright 2021 Dove Press. (d) Schematic illustration of ¹⁸F‐radiolabeled organosilicon fluoride receptor‐derived polymeric core‐shell nanoparticles (SiFA) for PET imaging. Reproduced with permission from Berke et al. (2018) Copyright 2018 American Chemical Society.

FIGURE 6

(a) Schematic overview of the imaging setup during treatment. Baseline ¹⁸F‐FDG PET/CT scans were obtained. Patients then received ⁸⁹Zr‐CPC634 within 2 h after the first therapeutic cycle. Follow‐up PET/CT scans were conducted at 24, 96 and 144 h post‐injection. (b) MIP images showing ¹⁸F‐FDG PET and on‐treatment ⁸⁹Zr‐CPC634 PET scans for a representative patient (patient 7) with adenocarcinoma of unknown primary. The black arrows highlight the accumulation of ⁸⁹Zr‐CPC634 in a bone metastasis. (c) Representative tumor accumulation examples at 96 h post‐injection with arrows indicating tumor lesions, showcasing both on‐treatment and diagnostic dose imaging. Reproduced with permission from Miedema et al. (2022), Copyright 2022 John Wiley and Sons.

FIGURE 7

(a) The schematic illustrated PET imaging of ⁸⁹Zr‐labeled high‐density lipoprotein nanoparticles, showing tumor uptake in patients with esophageal cancer. (b) Maximum‐intensity projections of consecutive PET images using ⁸⁹Zr‐HDL in Patient 1. (c) PET/CT scans of patient 6 diagnosed with esophageal adenocarcinoma. (d) No correlation was observed between the uptake of ¹⁸F‐FDG and ⁸⁹Zr‐HDL in tumors. Reproduced with permission from K. H. Zheng et al. (2022), Copyright 2022 Journal of Nuclear Medicine. (e) PET/CT images with volume rendering (on the left and right) and axial views (in the middle). Reproduced with permission from Doughton et al. (2018), Copyright 2018 Journal of Nuclear Medicine.