Nanoagents Based on Poly(ethylene glycol)‐b‐Poly(l‐thyroxine) Block Copolypeptide for Enhanced Dual‐Modality Imaging and Targeted Tumor Radiotherapy

Abstract

Future healthcare requires development of novel theranostic agents that are capable of not only enhancing diagnosis and monitoring therapeutic responses but also augmenting therapeutic outcomes. Here, a versatile and stable nanoagent is reported based on poly(ethylene glycol)‐b‐poly(l‐thyroxine) (PEG‐PThy) block copolypeptide for enhanced single photon emission computed tomography/computed tomography (SPECT/CT) dual‐modality imaging and targeted tumor radiotherapy in vivo. PEG‐PThy acquired by polymerization of l‐thyroxine‐N‐carboxyanhydride (Thy‐NCA) displays a controlled Mn, high iodine content of ≈49.2 wt%, and can spontaneously form 65 nm‐sized nanoparticles (PThyN). In contrast to clinically used contrast agents like iohexol and iodixanol, PThyN reveals iso‐osmolality, low viscosity, and long circulation time. While PThyN exhibits comparable in vitro CT attenuation efficacy to iohexol, it greatly enhances in vivo CT imaging of vascular systems and soft tissues. PThyN allows for surface decoration with the cRGD peptide achieving enhanced CT imaging of subcutaneous B16F10 melanoma and orthotopic A549 lung tumor. Taking advantages of a facile iodine exchange reaction, 125I‐labeled PThyN enables SPECT/CT imaging of tumors and monitoring of PThyN biodistribution in vivo. Besides, 131I‐labeled and cRGD‐functionalized PThyN displays remarkable growth inhibition of the B16F10 tumor in mice (tumor inhibition rate > 89%). These poly(l‐thyroxine) nanoparticles provide a unique and versatile theranostic platform for varying diseases.

Advances and Perspectives of Peptide and Polypeptide‐Based Materials for Biomedical Imaging

“…Deng and co-workers reported a block copolypeptide for SPECT/CT dual-modality imaging. [131] Different from the common strategy to only load radionuclides for SPECT, they modified polypeptide with both iodinated molecules for enhanced CT and 125 I for SPECT. They utilized iodineexchange reaction to easily label 125 I on the iodinated side chain of polypeptide.…”

“…Also, H&E staining results showed negligible damage on major organs including spleen and liver, which indicated the excellent biocompatibility of this polypeptide-based platform. Furthermore, 131 I could also be introduced into this polypeptide platform with iodine-exchange reaction, indicating the potential to combine enhanced imaging and radiotherapy.…”

Cancer Nanomedicines Based on Synthetic Polypeptides

“…showed efficient uptake and superb antiproliferative activity in B16F10 melanoma and HCT-116 tumor cells, respectively, leading to significantly more effective inhibition of both tumor models than nontargeted controls. , cRGD-decorated lipopepsomes (cRGD-LPP) revealed high loading and targeted delivery of DOX·HCl to an orthotopic A549 human lung tumor in nude mice, resulting in a significantly improved survival rate as compared to nontargeted counterpart and clinically used liposomal DOX (Lipo-DOX) . Robust and versatile nanoagents developed from PEG- b -poly­( l -thyroxine) following cRGD functionalization have exhibited enhanced single photon emission computed tomography/computed tomography (SPECT/CT) dual-modality imaging and targeted radiotherapy in subcutaneous B16F10 melanoma and orthotopic A549 lung tumor . Of note, selective cell penetrating CPP33 peptide-functionalized chimaeric lipopepsomes were developed from PEG–PAPA-PLys for selective delivery of siPLK1 to A549 human lung cancer cells in vivo, inducing effective tumor suppression and prolonged survival time .…”

“…72 Robust and versatile nanoagents developed from PEG-b-poly(L-thyroxine) following cRGD functionalization have exhibited enhanced single photon emission computed tomography/computed tomography (SPECT/CT) dual-modality imaging and targeted radiotherapy in subcutaneous B16F10 melanoma and orthotopic A549 lung tumor. 73 Of note, selective cell penetrating CPP33 peptide-functionalized chimaeric lipopepsomes were developed from PEG− PAPA-PLys for selective delivery of siPLK1 to A549 human lung cancer cells in vivo, inducing effective tumor suppression and prolonged survival time. 74 In a recent study, antihuman tissue factor antibody fragment (Fab′)-installed PIC micelles were constructed from PEG−PLys and siRNA, and the results showed that three molecules of Fab′-installed PIC micelles had the highest binding affinity and the most efficient gene silencing activity in pancreatic cancer BxPC3 cells compared with one or two molecule(s) of Fab′-installed PIC micelles, and exhibited high penetrability in BxPC3 spheroids.…”

Fabrication of PEGylated porphyrin/reduced graphene oxide/doxorubicin nanoplatform for tumour combination therapy

“…As references have reported, the combined application of PDT or PTT with other therapeutic tools can effectively overcome the above mentioned issues with reduced dosage and improved therapy efficacy 9,19–22 . For example, the Liu group reported a facile and low‐cost approach to designing a di‐functional nanoplatform (CuS@mSiO 2 ‐PEG) as a NIR light responsive drug delivery system for efficient chemo‐photothermal therapy 9 .…”