Cancer Theranostic Applications Research Articles

Progress on carbon dots and hydroxyapatite based biocompatible luminescent nanomaterials for cancer theranostics

Despite the significant advancement in cancer diagnosis and therapy, a huge burden remains. Consequently, much research has been diverted on the development of multifunctional nanomaterials for improvement in conventional diagnosis and therapy. Luminescent nanomaterials offer a versatile platform for the development of such materials as their intrinsic photoluminescence (PL) property offers convergence of diagnosis as well as therapy at the same time. However, the clinical translation of nanomaterials faces various challenges, including biocompatibility and cost-effective scale up production. Thus, luminescent materials with facile synthesis approach along with intrinsic biocompatibility and anticancerous activity hold significant importance. As a result, carbon dots (CDs) and nanohydroxyapatite (nHA) have attracted much attention for the development of optical imaging probes. CDs are the newest members of the carbonaceous nanomaterials family that possess intrinsic luminescent and therapeutic properties, making them a promising candidate for cancer theranostic. Additionally, nHA is an excellent bioactive material due to its compositional similarity to the human bone matrix. The nHA crystal can efficiently host rare-earth elements to attain luminescent property, which can further be implemented for cancer theranostic applications. Herein, the development of CDs and nHA based nanomaterials as multifunctional agents for cancer has been briefly discussed. The emphasis has been given to different synthesis strategies leading to different morphologies and tunable PL spectra, followed by their diverse applications as biocompatible theranostic agents. Finally, the review has been summarized with the current challenges and future perspectives.

Emerging Roles of Green-Synthesized Chalcogen and Chalcogenide Nanoparticles in Cancer Theranostics

The last few decades have seen an overwhelming increase in the amount of research carried out on the use of inorganic nanoparticles. More fascinating is the tremendous progress made in the use of chalcogen and chalcogenide nanoparticles in cancer theranostics. These nanomaterials, which were initially synthesized through chemical methods, have now been efficiently produced using different plant materials. The paradigm shift towards the biogenic route of nanoparticle synthesis stems from its superior advantages of biosafety, eco-friendliness, and simplicity, among others. Despite a large number of reviews available on inorganic nanoparticle synthesis through green chemistry, there is currently a dearth of information on the green synthesis of chalcogens and chalcogenides for cancer research. Nanoformulations involving chalcogens such as sulfur, selenium, and tellurium and their respective chalcogenides have recently emerged as promising tools in cancer therapeutics and diagnosis. Similar to other inorganic nanoparticles, chalcogens and chalcogenides have been synthesized using plant extracts and their purified biomolecules. In this review, we provide an up-to-date discussion of the recent progress that has been made in the plant-mediated synthesis of chalcogens and chalcogenides with a special focus on their application in cancer theranostics.

Metal-Phenolic Networks as Versatile Coating Materials for Biomedical Applications.

Polyphenols are naturally derived organic compounds that have long been used as food additives, antioxidants, and adhesives owing to their intrinsic physicochemical properties. Recently, there has been growing interest in the fabrication of coordination networks based on the self-assembly of polyphenols and metal ions, termed metal-phenolic networks (MPNs), for multiple biological applications including bioimaging, drug delivery, and cell encapsulation. The as-synthesized MPN complexes feature pH responsiveness, controllable size and rigidity, and tunable permeability based on the choice of polyphenol-metal ion pairs. The aim of this Review is to introduce the physicochemical properties of MPNs, highlight their recent biological applications in cancer theranostics and single-cell encapsulation, and discuss the future utility of MPNs for biomedical applications.

Fuel-Powered DNA Nanomachines for Biosensing and Cancer Therapy.

Inspired by biological motors, various artificial nanomachines and DNA motors have been fabricated to manipulate their motion on the nanometer scale, due to the high predictability and programmability of Watson-Crick base pairing. Among them, a fuel-powered DNA nanomachine is essentially a toehold-mediated strand exchange reaction and its driving force mainly comes from the hybridization of fuel DNA. It can be initiated by an input strand and automatically operate with the assistance of fuel DNA, realizing input strand recycle and signal amplification. Meanwhile, it is used as a carrier to load various drugs, such as Dox, siRNA and photosensitizers. Due to its excellent cellular penetrability and biocompatibility, fuel-powered DNA nanomachine usually enables operation inside living systems to execute all kinds of specific tasks according to the well-designed DNA strand displacement reaction, such as biomarker imaging, DNA computing and cancer theranostic applications. Therefore, as a catalytic amplification strategy and intelligent drug release platform, fuel-powered DNA nanomachine has attracted widespread attention in biosensors and cancer therapy. Hence, we present a Review on the design mechanism of fuel-powered DNA nanomachines and recent research advances in bioimaging and cancer therapy. It is hoped that this Review will provide the constructive direction for the design of fuel-powered DNA nanomachines and their applications in biological analysis and cancer treatment.

P-208 - Hypoxia targeting lutetium-177 labeled gold nanoparticles for cancer theranostic application

P-208 - Hypoxia targeting lutetium-177 labeled gold nanoparticles for cancer theranostic application

Polyacrylic Acid Nanoplatforms: Antimicrobial, Tissue Engineering, and Cancer Theranostic Applications.

Polyacrylic acid (PAA) is a non-toxic, biocompatible, and biodegradable polymer that gained lots of interest in recent years. PAA nano-derivatives can be obtained by chemical modification of carboxyl groups with superior chemical properties in comparison to unmodified PAA. For example, nano-particles produced from PAA derivatives can be used to deliver drugs due to their stability and biocompatibility. PAA and its nanoconjugates could also be regarded as stimuli-responsive platforms that make them ideal for drug delivery and antimicrobial applications. These properties make PAA a good candidate for conventional and novel drug carrier systems. Here, we started with synthesis approaches, structure characteristics, and other architectures of PAA nanoplatforms. Then, different conjugations of PAA/nanostructures and their potential in various fields of nanomedicine such as antimicrobial, anticancer, imaging, biosensor, and tissue engineering were discussed. Finally, biocompatibility and challenges of PAA nanoplatforms were highlighted. This review will provide fundamental knowledge and current information connected to the PAA nanoplatforms and their applications in biological fields for a broad audience of researchers, engineers, and newcomers. In this light, PAA nanoplatforms could have great potential for the research and development of new nano vaccines and nano drugs in the future.

Development, Therapeutic Evaluation and Theranostic Applications of Cubosomes on Cancers: An Updated Review.

Cancer is a group of disorders characterized by aberrant gene function and alterations in gene expression patterns. In 2020, it was anticipated that 19 million new cancer cases would be diagnosed globally, with around 10 million cancer deaths. Late diagnosis and interventions are the leading causes of cancer-related mortality. In addition, the absence of comprehensive cancer therapy adds to the burden. Many lyotropic non-lamellar liquid-crystalline-nanoparticle-mediated formulations have been developed in the last few decades, with promising results in drug delivery, therapeutics, and diagnostics. Cubosomes are nano-structured liquid-crystalline particles made of specific amphiphilic lipids in particular proportions. Their ability to encapsulate lipophilic, hydrophilic, and amphiphilic molecules within their structure makes them one of a kind. They are biocompatible, versatile drug carriers that can deliver medications through various routes of administration. Many preclinical studies on the use of cubosomes in cancer treatment and theranostic applications have been conducted. However, before cubosomes may be employed in clinical practice, significant technical advances must be accomplished. This review summarizes the development of cubosomes and their multifunctional role in cancer treatment based on the most recent reports.

A Facile and Universal Method for Preparing Polyethylene Glycol-Metal Hybrid Nanoparticles and Their Application in Tumor Theranostics.

Metal ions are of widespread interest owing to their brilliant biomedical functions. However, a simple and universal nanoplatform designed for assembling a range of functional metal ions has not been explored. In this study, a concept of polyethylene glycol (PEG)-mediated transport of metal ions is proposed. 31 types of PEG-metal hybrid nanoparticles (P-MNPs) are successfully synthesized through anionic ring-opening polymerization (ROP), "thiol-ene" click reaction, and subsequent incorporation with multiple metal ions. Compared with other methods, the facile method proposed in this study can provide a feasible approach to design MNPs (mostly <200nm)containing different metal ions and thus to explore their potential for cancer theranostics. As a proof-of-concept demonstration, four types P-MNPs, i.e., PEG-metal hybrid copper nanoparticles (PEG-Cu NPs), ruthenium nanoparticles (PEG-Ru NPs), and manganese nanoparticles (PEG-Mn NPs) or gadolinium nanoparticles (PEG-Gd NPs), are proven to be tailored for chemodynamic therapy, photothermal therapy, and magnetic resonance imaging of tumors, respectively. Overall, this study provides several metal ions-based nanomaterials with versatile functions for broad applications in cancer theranostics. Furthermore, it offers a promising tool that can be utilized for processing other metal-based nanoparticles and exploring their potential in the biomedical field.

Biodegradable 2D GeP nanosheets with high photothermal conversion efficiency for multimodal cancer theranostics

• Discovery of a new indirect bandgap phosphorus-based 2 D materials with a super photothermal conversion efficiency of 68.6 %. • Multimodal-imaging-Guided drug delivery of GeP nanosheets based platform for cancer. • GeP nanosheets based platform with excellent biodegradation and biocompatibility. • Stimulative responsive drug releasing and tumor inhibition of the GeP nanosheets based hybrid platform. Germanium phosphide (GeP), a new member of phosphorus-based 2D materials, is a semiconductor with indirect and narrowed band gap, which theoretically would have great potential to serve as near-infrared (NIR) photothermal agent (PTA) with high photothermal conversion efficiency (PTCE). However, the photothermal conversion performance and biomedical application of GeP-based nanocarriers has not been explored yet. Herein, we demonstrate the GeP nanosheets as high-performance PTA with PTCE of 68.6% in NIR region, which is much higher than many of other 2D PTA such as graphene, Mxenes, transition metal dichalcogenides, and black phosphorus (BP), and explore its application in multimodal cancer theranostics. Similar to BP nanosheets, the GeP nanosheets are biodegradable with excellent biocompatibility. With the merit of large specific surface area, the GeP nanosheets have high loading capacity (134 wt%) for anticancer drug Doxorubicin (DOX). The NH 2 -PEG-FA modified GeP-DOX hybrids show pH-responsive, heat-stimulative and sustained-drug-release performance as chemo-photothermal synergistic cancer therapy platform, and demonstrate remarkable tumor ablation ability both in vitro and in vivo . Meanwhile, multimodal imaging capability including photoacoustic imaging and photothermal imaging is also realized on basis of the excellent photothermal performance of GeP nanosheets. This study highlights the great promise of 2D GeP nanosheets as multifunctional platform for cancer theranostics application.

Synthesis, characterization, and optimization of Co-, Mn-, and Zn-substituted ferrite nanoparticles and nanoclusters for cancer theranostic applications

Synthesis, characterization, and optimization of Co-, Mn-, and Zn-substituted ferrite nanoparticles and nanoclusters for cancer theranostic applications

Design of Magnetic Nanoplatforms for Cancer Theranostics.

Cancer is the top cause of death globally. Developing smart nanomedicines that are capable of diagnosis and therapy (theranostics) in one–nanoparticle systems are highly desirable for improving cancer treatment outcomes. The magnetic nanoplatforms are the ideal system for cancer theranostics, because of their diverse physiochemical properties and biological effects. In particular, a biocompatible iron oxide nanoparticle based magnetic nanoplatform can exhibit multiple magnetic–responsive behaviors under an external magnetic field and realize the integration of diagnosis (magnetic resonance imaging, ultrasonic imaging, photoacoustic imaging, etc.) and therapy (magnetic hyperthermia, photothermal therapy, controlled drug delivery and release, etc.) in vivo. Furthermore, due to considerable variation among tumors and individual patients, it is a requirement to design iron oxide nanoplatforms by the coordination of diverse functionalities for efficient and individualized theranostics. In this article, we will present an up–to–date overview on iron oxide nanoplatforms, including both iron oxide nanomaterials and those that can respond to an externally applied magnetic field, with an emphasis on their applications in cancer theranostics.

Eco-friendly synthesis of carbon nanotubes and their cancer theranostic applications.

Carbon nanotubes (CNTs) with attractive physicochemical characteristics such as high surface area, mechanical strength, functionality, and electrical/thermal conductivity have been widely studied in different fields of science. However, the preparation of these nanostructures on a large scale is either expensive or sometimes ecologically unfriendly. In this context, plenty of studies have been conducted to discover innovative methods to fabricate CNTs in an eco-friendly and inexpensive manner. CNTs have been synthesized using various natural hydrocarbon precursors, including plant extracts (e.g., tea-tree extract), essential oils (e.g., eucalyptus and sunflower oil), biodiesel, milk, honey, and eggs, among others. Additionally, agricultural bio-wastes have been widely studied for synthesizing CNTs. Researchers should embrace the usage of natural and renewable precursors as well as greener methods to produce various types of CNTs in large quantities with the advantages of cost-effectiveness and environmentally benign features. In addition, multifunctionalized CNTs with improved biocompatibility and targeting features are promising candidates for cancer theranostic applications owing to their attractive optical, chemical, thermal, and electrical properties. This perspective discusses the recent developments in eco-friendly synthesis of CNTs using green chemistry-based techniques, natural renewable resources, and sustainable catalysts, with emphasis on important challenges and future perspectives and highlighting techniques for the functionalization or modification of CNTs. Significant and promising cancer theranostic applications as well as their biocompatibility and cytotoxicity issues are also discussed.

MnCO3-mineralized polydopamine nanoparticles as an activatable theranostic agent for dual-modality imaging-guided photothermal therapy of cancers.

Background: Single imaging modality is still insufficient to evaluate the biological and anatomical structures of tumors with high accuracy and reliability. Generation of non-specific contrast, leading to a low target-to-background signal ratio, results in low imaging resolution and accuracy. Tumor environment-specific activatable multifunctional contrast agents need to maximize the contrast signals, representing a dual imaging-guided photothermal therapy (PTT) at target tumor sites.Methods: Cellular uptake, cytotoxicity assay, and in vitro photothermal conversion efficiency of MnCO3-mineralized fluorescent polydopamine nanoparticles (MnCO3-FPNPs) were evaluated using 4T1 breast cancer cells. In vivo dual-modality imaging was performed using IVIS imaging and a 4.7 T animal MRI systems after injection into 4T1 tumor-bearing nude mice. The effects of photothermal therapeutic through PTT were measured after irradiation with an 808 nm laser (1.5 W/cm2) for 10 min, measuring the size of the tumors every 2 days.Results: At physiological pH (7.4), MnCO3-FPNP is efficiently quenched. Conversely, at acidic pH (5.4), the strong fluorescence (FL) is recovered due to the dissociation of Mn2+ from the FPNPs. At pH 7.4, MnCO3-FPNP activity is silenced to enhance water proton relaxation due to unionized MnCO3 maintenance; conversely, at acidic pH (5.4), MnCO3-FPNPs efficiently release Mn2+ ions, thereby resulting in T1-weighted magnetic resonance (MR) contrast enhancement. MnCO3-FPNPs display a promising diagnostic ability for 4T1 breast cancer xenograft models, as well as exhibit a high photothermal conversion efficiency. A successful tumor treatment via their photothermal activity is accomplished within 14 days.Conclusions: Our studies exhibited unique “OFF-ON” activation abilities in FL/MR dual imaging and PTT functions. This approach suggests that the MnCO3-FPNPs may serve as a useful platform for various mineralization-based multimodal imaging-guided PTT models for many cancer theranostic applications.

“Nano effects”: a review on nanoparticle-induced multifarious systemic effects on cancer theranostic applications

The advent of nanotechnology has broadened the scope of technological advances in both medical and industrial applications.

Receptor-Targeted Surface-Engineered Nanomaterials for Breast Cancer Imaging and Theranostic Applications.

Breast cancer is one of the most frequently diagnosed cancers in women and the major cause of worldwide cancer-related deaths among women. Various treatment strategies including conventional chemotherapy, immunotherapy, gene therapy, gene silencing and deliberately engineered nanomaterials for receptor mediated targeted delivery of anticancer drugs, antibodies, and small-molecule inhibitors, etc are being investigated by scientists to combat breast cancer. Smartly designed/fabricated nanomaterials are being explored to target breast cancer through enhanced permeation and retention effect; and also, being conjugated with suitable ligand for receptor-mediated endocytosis to target breast cancer for diagnostic, and theranostic applications. These receptor-targeted nanomedicines have shown efficacy to target specific tumor tissue/cells abstaining the healthy tissues/cells from cytotoxic effect of anticancer drug molecules. In the last few decades, theranostic nanomedicines have gained much attention among other nanoparticle systems due to their unique ability to deliver chemotherapeutic as well as diagnostic agents, simultaneously. Theranostic nanomaterials are emerging as novel paradigm with ability for concurrent delivery of imaging (with contrasting agents), targeting (with biomarkers), and anticancer therapeutics with one delivery system (as cancer theranostics) and can transpire as promising strategy to overcome various hurdles for effective management of breast cancer including its most aggressive form, triple-negative breast cancer.

An Endogenous miRNA-Initiated Hybridization Chain Reaction and Subsequent DNAzyme Activation for Cellular Theranostics

An Endogenous miRNA-Initiated Hybridization Chain Reaction and Subsequent DNAzyme Activation for Cellular Theranostics

Oral Cancer Theranostic Application of FeAu Bimetallic Nanoparticles Conjugated with MMP-1 Antibody.

Metastatic oral squamous cell carcinoma (SCC) displays a poor disease prognosis with a 5-year survival rate of 39%. Chemotherapy has emerged as the mainstream treatment against small clusters of cancer cells but poses more risks than benefits for metastatic cells due to the non-specificity and cytotoxicity. To overcome these obstacles, we conjugated antibodies specific for matrix metalloproteinase-1 (MMP-1), a prognostic biomarker of SCC, to iron–gold bimetallic nanoparticles (FeAu NPs) and explored the capability of this complex to target and limit SSC cell growth via magnetic field-induced hyperthermia. Our results showed that 4.32 ± 0.79 nm sized FeAu NPs were superparamagnetic in nature with a saturation magnetization (Ms) of 5.8 emu/g and elevated the media temperature to 45 °C, confirming the prospect to deliver hyperthermia. Furthermore, conjugation with MMP-1 antibodies resulted in a 3.07-fold higher uptake in HSC-3 (human tongue squamous cell carcinoma) cells as compared to L929 (fibroblast) cells, which translated to a 5-fold decrease in cell viability, confirming SCC targeting. Finally, upon magnetic stimulation, MMP-1-FeAu NPs conjugate triggered 89% HSC-3 cellular death, confirming the efficacy of antibody-conjugated nanoparticles in limiting SCC growth. The synergistic effect of biomarker-specific antibodies and magnetic nanoparticle-induced hyperthermia may open new doors towards SCC targeting for improved disease prognosis.

Data-Driven Modeling of Breast Cancer Tumors Using Boolean Networks.

Cancer is a genomic disease involving various intertwined pathways with complex cross-communication links. Conceptually, this complex interconnected system forms a network, which allows one to model the dynamic behavior of the elements that characterize it to describe the entire system’s development in its various evolutionary stages of carcinogenesis. Knowing the activation or inhibition status of the genes that make up the network during its temporal evolution is necessary for the rational intervention on the critical factors for controlling the system’s dynamic evolution. In this report, we proposed a methodology for building data-driven boolean networks that model breast cancer tumors. We defined the network components and topology based on gene expression data from RNA-seq of breast cancer cell lines. We used a Boolean logic formalism to describe the network dynamics. The combination of single-cell RNA-seq and interactome data enabled us to study the dynamics of malignant subnetworks of up-regulated genes. First, we used the same Boolean function construction scheme for each network node, based on canalyzing functions. Using single-cell breast cancer datasets from The Cancer Genome Atlas, we applied a binarization algorithm. The binarized version of scRNA-seq data allowed identifying attractors specific to patients and critical genes related to each breast cancer subtype. The model proposed in this report may serve as a basis for a methodology to detect critical genes involved in malignant attractor stability, whose inhibition could have potential applications in cancer theranostics.

PEGylated Nanoscale Metal-Organic Frameworks for Targeted Cancer Imaging and Drug Delivery.

Nanoscale metal-organic frameworks (nMOFs) are a unique type of hybrid materials, which are broadly applicable as cargo delivery systems. However, the relatively low material stability and insufficient cancer cell interacting capacity have limited nMOFs' applications in cancer theranostics. Herein, a zirconium-based nMOF UiO-66-N3 was synthesized, and its surface was covalently functionalized with alkyne-containing polyethylene glycol (PEG) via the azide-alkyne click chemistry. After that, F3 peptide was attached for targeting of cancer cells (the material was denoted as UiO-66-PEG-F3). Doxorubicin (DOX) served as a therapeutic drug and a fluorescent label in this study, and it was transported into UiO-66-PEG conjugates with sufficient drug loading efficiency. pH-responsive release of DOX from UiO-66 conjugates was witnessed. The structural integrity of UiO-66-N3 was maintained post the surface modification process. Flow cytometry and confocal fluorescence microscopy revealed that DOX/UiO-66-PEG-F3 had stronger accumulation in MDA-MB-231 cells (nucleolin+) compared with DOX/UiO-66-PEG. In order to track the pharmacokinetic behavior (organ distribution profile) in vivo, the positron-emitting zirconium-89 (89Zr) was incorporated into UiO-66-N3. Similar PEGylation and F3 peptide conjugation resulted in the formation of 89Zr-UiO-66-PEG-F3. Serial positron emission tomography (PET) imaging demonstrated that the preferential accumulation of 89Zr-UiO-66-PEG-F3 in MDA-MB-231 tumors, and their liver clearance was faster than PEGylated UiO-66 using noncovalent methods. Thus, the PEGylated nMOFs using covalent strategies may find broad application in future cancer theranostics.

Mitochondrion-Anchored Photosensitizer with Near Infrared-I Aggregation-Induced Emission for Near Infrared-II Two-Photon Photodynamic Therapy.

Two-photon photodynamic therapy (2P-PDT) that employs photosensitizers (PSs) with 2P absorption is particularly intriguing in cancer treatment, in that 2P excitation enables precise spatial localization and deep tissue penetration. Here, a donor-π-acceptor PS (named TPBPy) with near infrared (NIR) aggregation-induced emission (AIE) is designed and synthesized for imaging-guided 2P-PDT. The maximal photoluminescence (PL) peak of TPBPy is as high as 720nm when it is encapsulated in liposomes. Upon 2P irradiation by a laser in NIR-II window (λ=1000nm), TPBPy exhibits strong NIR-I PL in a multicellular tumor spheroids (MCTSs) model, showing an imaging depth of 210µm that is significantly higher than upon one-photon irradiation. Moreover, TPBPy localizes specifically on mitochondrion, an important organelle in cell oxidative metabolism and apoptosis. When exposed to the NIR-II irradiation, TPBPy can efficiently generate singlet oxygen (1 O2 ) and trigger cell death. The efficacy of TPBPy-mediated 2P-PDT has also been validated using 4T1 tumor mouse model, the growth of which is significantly suppressed upon NIR-II laser irradiation. TPBPy herein serves as an excellent candidate to suppress deep tumor tissues through NIR-II 2P-PDT, and also renders a new paradigm to construct mitochondrion-anchored AIE luminogens for future cancer theranostic applications.