Theranostics - a sure cure for cancer after 100 years?

Abstract

Cancer has remained a formidable challenge in medicine and has claimed an enormous number of lives worldwide. Theranostics, combining diagnostic methods with personalized therapeutic approaches, shows huge potential to advance the battle against cancer. This review aims to provide an overview of theranostics in oncology: exploring its history, current advances, challenges, and prospects. We present the fundamental evolution of theranostics from radiotherapeutics, cellular therapeutics, and nanotherapeutics, showcasing critical milestones in the last decade. From the early concept of targeted drug delivery to the emergence of personalized medicine, theranostics has benefited from advances in imaging technologies, molecular biology, and nanomedicine. Furthermore, we emphasize pertinent illustrations showcasing that revolutionary strategies in cancer management enhance diagnostic accuracy and provide targeted therapies customized for individual patients, thereby facilitating the implementation of personalized medicine. Finally, we describe future perspectives on current challenges, emerging topics, and advances in the field.

Keywords: cancer; nanotheranostics; personalized medicine; radiotheranostics; synthetic biology.

Figure 1

Illustration of radiotheranostics. Adapted with permission from , Copyright 2023 Springer Nature.

Figure 2

Clinical application in radiotheranostics. A. [¹⁷⁷Lu]Lu-DOTATATE planar scans (left) and isodose curves (right) of a patient with G2 neuroendocrine tumor (ileum) after injection of [¹⁷⁷Lu]Lu-DOTATATE. B. Corresponding [¹⁷⁷Lu]Lu-DOTA-JR11 planar scans (left) and isodose curves (right) after injection of [¹⁷⁷Lu]Lu-DOTA-JR11. Adapted with permission from , Copyright 2014 Society of Nuclear Medicine and Molecular Imaging. C. A 75-year-old post-radical prostatectomy patient exhibited intense uptake on [⁶⁸Ga]Ga-PSMA PET, indicating a single lymph node metastasis confirmed by biopsy (left); a 58-year-old patient with mCRPC showed multiple systemic metastases in baseline and significant improvement in post-treatment [⁶⁸Ga]Ga-PSMA-11 PET/CT after [¹⁷⁷Lu]Lu-PSMA-I&T therapy (right). Adapted with permission from , , Copyright 2015 Society of Nuclear Medicine and Molecular Imaging and 2022 Frontiers Media S.A. D. A 79-year-old mCRPC patient responded to initial [¹⁷⁷Lu]Lu-PSMA treatment but experienced disease progression, showing a significant response to subsequent [²²⁵Ac]Ac-PSMA-I&T therapy. Adapted with permission from , Copyright 2014 Society of Nuclear Medicine and Molecular Imaging.

Figure 3

Advancements in radiotheranostics targeting novel biomarkers. A. Targeting the chemokine CXCR4 with Pentixafor/Pentixather. Adapted with permission from , Copyright 2023 Society of Nuclear Medicine and Molecular Imaging. B. Initial results of peptide-receptor radionuclide therapy with [¹⁷⁷Lu]Lu-FAP-2286. Adapted with permission from , Copyright 2022 Society of Nuclear Medicine and Molecular Imaging.

Figure 4

Clinical application of representive PSMA-617 albumin-binding derivatives. A. Preclinical survival impact in mice from [¹⁷⁷Lu]Lu-PSMA-ALB-56 vs. [¹⁷⁷Lu]Lu-PSMA-617 treatment (left) and clinical SPECT images of [¹⁷⁷Lu]Lu-PSMA-ALB-56 (right). Adapted with permission from , , Copyright 2022 Society of Nuclear Medicine and Molecular Imaging and 2020 Springer Nature. B. Representative mCRPC patients for [⁶⁸Ga]Ga-PSMA PET/CT and PSA response evaluation in the phase 1 trial to determine the maximum tolerated dose and patient‐specific dosimetry of [¹⁷⁷Lu]Lu‐LNC1003. Adapted with permission from , Copyright 2022 Springer Nature.

Figure 5

Representative nanomaterials for NIR-II imaging guided theranostics. A. Imaging of neck lymph and blood vessels with the molecular complex EB766 and downconversion NPs, cross-sectional intensity profile along the white dashed line. Mouse hindlimb lymph structures (EB766) and blood vessels (downconversion NPs) in different regions of a mouse and cross-sectional intensity profile along the white dashed line. Scale bars, 4 mm. Adapted with permission from , Copyright 2021 Springer Nature. B. Schematic illustration of NIR-II emissive AIEgen photosensitizer PTZ-TQ that enables ultrasensitive imaging-guided surgery and phototherapy to fully inhibit orthotopic hepatic tumors. Adapted with permission from , Copyright 2021 Springer Nature.

Figure 6

Representative work of fractionated delivery of singlet oxygen for cancer theranostics. A. Illustration of the nanoformulation structure. Adapted with permission from , Copyright 2020 Wiley-VCH B. Anthracene functionalized photosensitizers for fractionated delivery of singlet oxygen with enhanced phototheranostics. Adapted with permission from , Copyright 2021 Wiley-VCH.

Figure 7

Typical examples of designing type I photosensitizers for cancer theranostics. A. Preparation and characterization of NanoPcA by TEM and DLS. Adapted with permission from , Copyright 2020 Wiley-VCH. B. Illustration of molecular design of TFMN and TTFMN, mechanisms of type-I and II processes, construction of acid-activated TTFMN NPs, and their applications in precise photodynamic nuclear targeting cancer therapy. Adapted with permission from , Copyright 2021 Wiley-VCH.

Figure 8

A. Representative nanomaterials for sonotheranostics. Illustration of Dy-TCPP nanocrystals killing cancer cells by the combination treatment of SDT and immunotherapy. Adapted with permission from , Copyright 2023 Springer Nature publishing group. B. The preparation of MPIRx nanodrugs for SDT and CD47 inhibitors. Adapted with permission from , Copyright 2023 Elsevier publishing group.

Figure 9

Representative work of sonoafterglow theranostics. A. Illustration of sonoafterglow initiators and substrates. B. Molecular mechanism of sonoafterglow. Initiators generate ¹O₂ to convert substrate into active dioxetane substrates under ultrasound application, emitting afterglow luminescence. The luminescence can transfer back to sonosensitizer and re-emit at longer wavelength. Reproduced from ref with permission. Copyright 2023 Nature Publishing Group.

Figure 10

Representative work of nanomaterials for chemotheranostics. A. Synthesis and characterization of a spongy μCGP comprising multiple small NPs (nanoconstructs) dispersed within a porous PEG matrix. Adapted with permission from , Copyright 2023 Wiley-VCH. B. Schematic representation of nanohybrid MTX-NLPHS system formulation and its cellular internalization. Adapted with permission from , Copyright 2023 Ivyspring International Publisher.

Figure 11

Representative work of nanomaterials for chemo-CDT. A. Microfluidic synthesis of FDRF NCs for T1-MRI guided chemo-CDT of tumors. Adapted with permission from , Copyright 2023 Elsevier Publishing Group. B. Schematic illustration of TME-responsive HSPMH-DOX for activation MRI guided synergistic therapy. Adapted with permission from , Copyright 2023 Elsevier Publishing Group.