This comprehensive review provides an in-depth analysis of how nanotechnology has revolutionized cancer theragnostic, which combines diagnostic and therapeutic methods to customize cancer treatment. The study examines the unique attributes, uses, and difficulties linked to different types of nanoparticles, including gold, iron oxide, silica, Quantum dots, Carbon nanotubes, and liposomes, in the context of cancer treatment. In addition, the paper examines the progression of nanotheranostics, emphasizing its uses in precise medication administration, photothermal therapy, and sophisticated diagnostic methods such as MRI, CT, and fluorescence imaging. Moreover, the article highlights the capacity of nanoparticles to improve the effectiveness of drugs, reduce the overall toxicity in the body, and open up new possibilities for treating cancer by releasing drugs in a controlled manner and targeting specific areas. Furthermore, it tackles concerns regarding the compatibility of nanoparticles and their potential harmful effects, emphasizing the significance of continuous study to improve nanotherapeutic methods for use in medical treatments. The review finishes by outlining potential future applications of nanotechnology in predictive oncology and customized medicine. 

Nanoparticles in cancer theragnostic and drug delivery: A comprehensive review

Abstract Cancer remains one of the most challenging health issues globally, demanding innovative therapeutic approaches for effective treatment. Nanoparticles, particularly those composed of gold, silver, and iron oxide, have emerged as promising candidates for changing cancer therapy. This comprehensive review demonstrates the landscape of nanoparticle‐based oncological interventions, focusing on the remarkable advancements and therapeutic potentials of gold, silver, and iron oxide nanoparticles. Gold nanoparticles have garnered significant attention for their exceptional biocompatibility, tunable surface chemistry, and distinctive optical properties, rendering them ideal candidates for various cancer diagnostic and therapeutic strategies. Silver nanoparticles, renowned for their antimicrobial properties, exhibit remarkable potential in cancer therapy through multiple mechanisms, including apoptosis induction, angiogenesis inhibition, and drug delivery enhancement. With their magnetic properties and biocompatibility, iron oxide nanoparticles offer unique cancer diagnosis and targeted therapy opportunities. This review critically examines the recent advancements in the synthesis, functionalization, and biomedical applications of these nanoparticles in cancer therapy. Moreover, the challenges are discussed, including toxicity concerns, immunogenicity, and translational barriers, and ongoing efforts to overcome these hurdles are highlighted. Finally, insights into the future directions of nanoparticle‐based cancer therapy and regulatory considerations, are provided aiming to accelerate the translation of these promising technologies from bench to bedside. 

Advanced Nanomaterials for Cancer Therapy: Gold, Silver, and Iron Oxide Nanoparticles in Oncological Applications

Nanostructures and nanoparticles as medical diagnostic imaging contrast agents: A review

Abstract Background Previously, we discovered that human solid tumours, but not normal human tissues, preferentially overexpress interleukin‐13Receptor alpha2, a high binding receptor for IL‐13. To develop novel anti‐cancer approaches, we constructed a chimeric antigen receptor construct using a high binding and codon optimised scFv‐IL‐13Rα2 fragment fused with CD3ζ and co‐stimulatory cytoplasmic domains of CD28 and 4‐1BB. Methods We developed a scFv clone, designated 14‐1, by biopanning the bound scFv phages using huIL‐13Rα2Fc chimeric protein and compared its binding with our previously published clone 4‐1. We performed bioinformatic analyses for complementary determining regions (CDR) framework and residue analyses of the light and heavy chains. This construct was packaged with helper plasmids to produce CAR‐lentivirus and transduced human Jurkat T or activated T cells from peripheral blood mononuclear cells (PBMCs) to produce CAR‐T cells and tested for their quality attributes in vitro and in vivo. Serum enzymes including body weight from non‐tumour bearing mice were tested for assessing general toxicity of CAR‐T cells. Results The binding of 14‐1 clone is to IL‐13Rα2Fc‐chimeric protein is ∼5 times higher than our previous clone 4‐1. The 14‐1‐CAR‐T cells grew exponentially in the presence of cytokines and maintained phenotype and biological attributes such as cell viability, potency, migration and T cell activation. Clone 14‐1 migrated to IL‐13Rα2Fc and cell free supernatants only from IL‐13Rα2+ve confluent glioma tumour cells in a chemotaxis assay. scFv‐IL‐13Rα2‐CAR‐T cells specifically killed IL‐13Rα2+ve but not IL‐13Rα2‐ve tumour cells in vitro and selectively caused significant release of IFN‐γ only from IL‐13Rα2+ve co‐cultures. These CAR‐T cells regressed IL‐13Rα2+ve glioma xenografts in vivo without any general toxicity. In contrast, the IL‐13Rα2 gene knocked‐down U251 and U87 xenografts failed to respond to the CAR‐T therapy. Conclusion Taken together, we conclude that the novel scFv‐IL‐13Rα2 CAR‐T cell therapy may offer an effective therapeutic option after designing a careful pre‐clinical and clinical study. 

Identification and characterisation of novel CAR‐T cells to target IL13Rα2 positive human glioma in vitro and in vivo

Aluminum fluoride (AlF) complexes have been used over the past decade to incorporate [18F]fluoride into large biomolecules in a highly selective fashion by using relatively facile conditions. However, despite their widespread usage, there are a large number of variations in the reaction conditions, without a definitive discussion provided on the mechanism to understand how these changes would alter the end result. Herein, we report a detailed mechanistic investigation of the reaction, using a mixture of theoretical studies, fluorine-19 and fluorine-18 chemistry, and the consequences it has on the efficient clinical translation of AlF-containing imaging agents.

Investigating the Mechanism of Aluminum Fluoride Chelation.

Spectral CT imaging (multi-energy detection) is a promising imaging technique that can benefit from the use of high atomic number (high- Z ) based nanoparticles (NPs) as contrast agents. 

High atomic number nanoparticles to enhance spectral CT imaging aspects

Abstract Background Chimeric antigen receptor (CAR) T cell therapy is an exciting cell-based cancer immunotherapy. Unfortunately, CAR-T cell therapy is associated with serious toxicities such as cytokine release syndrome (CRS) and neurotoxicity. The mechanism of these serious adverse events (SAEs) and how homing, distribution and retention of CAR-T cells contribute to toxicities is not fully understood. Enabling in vitro methods to allow meaningful, sensitive in vivo biodistribution studies is needed to better understand CAR-T cell disposition and its relationship to both effectiveness and safety of these products. Methods To determine if radiolabelling of CAR-T cells could support positron emission tomography (PET)-based biodistribution studies, we labeled IL-13Rα2 targeting scFv-IL-13Rα2-CAR-T cells (CAR-T cells) with 89 Zirconium-oxine ( 89 Zr-oxine) and characterized and compared their product attributes with non-labeled CAR-T cells. The 89 Zr-oxine labeling conditions were optimized for incubation time, temperature, and use of serum for labeling. In addition, T cell subtype characterization and product attributes of radiolabeled CAR-T cells were studied to assess their overall quality including cell viability, proliferation, phenotype markers of T-cell activation and exhaustion, cytolytic activity and release of interferon-γ upon co-culture with IL-13Rα2 expressing glioma cells. Results We observed that radiolabeling of CAR-T cells with 89 Zr-oxine is quick, efficient, and radioactivity is retained in the cells for at least 8 days with minimal loss. Also, viability of radiolabeled CAR-T cells and subtypes such as CD4 + , CD8 + and scFV-IL-13Rα2 transgene positive T cell population were characterized and found similar to that of unlabeled cells as determined by TUNEL assay, caspase 3/7 enzyme and granzyme B activity assay. Moreover, there were no significant changes in T cell activation (CD24, CD44, CD69 and IFN-γ) or T cell exhaustion (PD-1, LAG-3 and TIM3) markers expression between radiolabeled and unlabeled CAR-T cells. In chemotaxis assays, migratory capability of radiolabeled CAR-T cells to IL-13Rα2Fc was similar to that of non-labeled cells. Conclusions Importantly, radiolabeling has minimal impact on biological product attributes including potency of CAR-T cells towards IL-13Rα2 positive tumor cells but not IL-13Rα2 negative cells as measured by cytolytic activity and release of IFN-γ. Thus, IL-13Rα2 targeting CAR-T cells radiolabeled with 89 Zr-oxine retain critical product attributes and suggest 89 Zr-oxine radiolabeling of CAR-T cells may facilitate biodistribution and tissue trafficking studies in vivo using PET. 

/pdf/characterization-of-chimeric-antigen-receptor-modified-t-259spquj.pdf

Characterization of chimeric antigen receptor modified T cells expressing scFv-IL-13Rα2 after radiolabeling with 89Zirconium oxine for PET imaging

A radiochemical synthesis of [18 F]DK222, a peptide binder of programmed death ligand 1 protein, suitable for human PET studies is described and results from validation productions are presented. The high specific activity radiotracer product is prepared as a sterile, apyrogenic solution that conforms to current Good Manufacturing Practice (cGMP) requirements. In addition, the production is extended to use a commercial synthesizer platform (General Electric FASTlab 2).

An Optimized Radiosynthesis of [18 F]DK222, a PET Radiotracer for Imaging PD-L1.

Correction for 'LHRH conjugated gold nanoparticles assisted efficient ovarian cancer targeting evaluated via spectral photon-counting CT imaging: a proof-of-concept research' by Dhiraj Kumar et al., J. Mater. Chem. B, 2023, 11, 1916-1928, https://doi.org/10.1039/D2TB02416K.

/pdf/correction-lhrh-conjugated-gold-nanoparticles-assisted-29du53hl.pdf

Correction: LHRH conjugated gold nanoparticles assisted efficient ovarian cancer targeting evaluated via spectral photon-counting CT imaging: a proof-of-concept research.

Purpose We aimed to develop a novel molecular imaging agent to monitor Multiple Myeloma (MM) using CD38, a target that has shown uniform expression in MM. However, only a few molecularly targeted imaging agents are available to take advantage of this high expression and the sensitivity of positron emission tomography (PET), and none of them fit into the standard clinical workflow. To address this, we developed and evaluated a first-in-class peptide-based radiotracer, [68Ga]Ga-AJ206, to non-invasively quantify CD38 levels in MM. Experimental design To quantify CD38 levels non-invasively, we synthesized a peptide-based high-affinity binder, tested its affinity by surface plasmon resonance, and evaluated a gallium-68–labeled analog for in vitro specificity. We also performed in vivo distribution, pharmacokinetics, and CD38 specificity evaluations in MM preclinical models, and cross-validated imaging data with flow cytometry and immunohistochemistry-based analysis of CD38 expression. Results [68Ga]Ga-AJ206 demonstrated CD38 binding specificity with a dissociation constant (KD) of 19.1±0.99 nM and in vitro binding dependent on CD38 expression. PET imaging with [68Ga]Ga-AJ206 showed high contrast within 60 min and suitable radiation dose estimates for clinical use. Additionally, [68Ga]Ga-AJ206 detected CD38 expression in xenograft and disseminated disease models in a manner consistent with immunohistochemistry-based detection. Conclusions [68Ga]Ga-AJ206 exhibited the salient features required for clinical translation, providing CD38-specific high contrast images and detecting varying levels of CD38 expression in bone disease and soft tissue metastases. STATEMENT OF TRANSLATIONAL RELEVANCE Multiple myeloma is a challenging bone marrow plasma cell disease that is associated with heterogenous responses and universal recurrence. While minimal residual disease monitoring by blood and invasive bone marrow samples have improved prognostication of disease recurrence, molecularly targeted non-invasive imaging options remain limited. Additionally, there is an unmet need for functional imaging agents to monitor the effects of new therapeutics targeting CD38 protein, which is highly expressed on MM cells. To address this gap, we report the development of a high affinity first-in-class gallium-68 labeled peptide radiotracer for CD38, [68Ga]Ga-AJ206. [68Ga]Ga-AJ206 provides high-contrast images by PET within the standard clinical workflow of 60 minutes. Furthermore, we have demonstrated the potential of [68Ga]Ga-AJ206 PET to measure varying levels of CD38 expression. Further development of this new radiotracer may complement existing technologies and improve prognostication and monitoring of therapy response in MM patients.

https://www.biorxiv.org/content/biorxiv/early/2023/05/12/2023.05.09.540036.full.pdf

A gallium-68-labeled peptide radiotracer for cd38-targeted imaging in multiple myeloma with pet

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