Cancer Theranostics Research Articles

Unveiling the Cytotoxic Potential of Quercetin-Loaded Magnetic Bacterial Bots against Cervical Cancer.

Bacterial bots are potent vehicles in cancer theranostics where bacteria are used typically as cargos for drug delivery. However, living bacteria themselves may aid in their efficiency in killing the tissues. For example, living bacteria may be functionalized with magnetic and luminescent nanoparticles along with drugs in order to achieve the targeted delivery and release of payloads that would include the bacteria. In this study, we elucidate the synergistic impact of human-friendly living Lactobacillus rhamnosus bacteria decorated with gold nanoclusters and quercetin-loaded magnetic nanoparticles against the HeLa-cervical cancer cells. The cytotoxicity of the fabricated magnetic bacterial bots within the low dose (5 × 105 CFU/mL) against the HeLa monolayer and 3D spheroid model was found around 84%, which had remarkably enhanced up to more than 91% in the presence of an external magnet. The antiproliferative action of magnetic bacterial bots was demonstrated by the escalation of generated reactive oxygen species from 1.8- to 2.3-fold. Cells treated with magnetic bacterial bots showed a decrease in lipid droplet content, along with altered cell cycle patterns, which led to 74% (average population) of cells being exposed to necroptosis. The study highlights the cytotoxic potential of magnetic bacterial bots against cervical cancer cells outweighing that of the quercetin or the bacteria only, ensuring an external-magnetic-field-responsive targeted drug delivery system.

Highly Photoreactive Semiconducting Polymers with Cascade Intramolecular Singlet Oxygen and Energy Transfer for Cancer-Specific Afterglow Theranostics.

Afterglow luminescence provides ultrasensitive optical detection by minimizing tissue autofluorescence and increasing the signal-to-noise ratio. However, due to the lack of suitable unimolecular afterglow scaffolds, current afterglow agents are nanocomposites containing multiple components with limited afterglow performance and have rarely been applied for cancer theranostics. Herein, we report the synthesis of a series of oxathiine-containing donor-acceptor block semiconducting polymers (PDCDs) and the observation of their high photoreactivity and strong near-infrared (NIR) afterglow luminescence. We reveal that PDCDs absorb NIR light to undergo a photodynamic process to generate singlet oxygen (1O2), which intramolecularly transfers to and efficiently reacts with the oxathiine block to form the afterglow oxathiine intermediates due to the low Gibbs free energy changes required for this photoreaction. Following intramolecular afterglow energy transfer from the oxathiine donor block to the acceptor block, NIR afterglow emission is produced from PDCDs. Owing to the efficient cascade intramolecular photochemical process, PDCD-based nanoparticles achieve a higher brightness and longer NIR emission compared to most reported afterglow agents, even after ultrashort photoirradiation for only 3 s. Furthermore, the cascade photochemical process within PDCD can be inhibited after bioconjugation with a quencher-linked peptide. This allows the construction of a cancer-activatable afterglow theranostic probe (CATP) that only switches on the afterglow signal and photodynamic function in the presence of a cancer-overexpressed enzyme. Thereby, CATP represents the first afterglow phototheranostic probe that permits cancer-specific detection and photodynamic cancer therapy under preclinical settings. In summary, this study provides a molecular guideline to develop afterglow probes from photoreactive polymers.

Research progress of near-infrared fluorescence imaging in accurate theranostics in bladder cancer.

With the highest 5-year recurrence rate among malignancies, bladder cancer is a relatively common type of cancer that typically originates from the urothelial cells lining the bladder. Additionally, bladder cancer is one of the most financially burdensome neoplasms to medical institutions in terms of management. Hence, prompt identification and accurate handling of bladder cancer are pivotal for enhancing patient prognosis. Optical imaging has experienced remarkable advancements in fundamental medical research owing to its cost-effectiveness and capacity for real-time imaging. The utilization of near-infrared imaging techniques has also become a prominent area of research in recent times. By effectively decreasing the adverse effects of light scattering and tissue autofluorescence, this technique offers a deeper penetration depth, a better signal-to-noise ratio of images, and a clear resolution for imaging. Thus, this article introduces the application of near-infrared fluorescence imaging in diagnosing and treating bladder cancer. Furthermore, the paper delves into the field's obstacles, possibilities, and upcoming prospects. Near-infrared fluorescence has advantages over white or blue light in theory and in most articles. However, the lack of penetration depth of NIR fluorescence imaging is still a challenge. Despite notable improvements in the depth of near-infrared fluorescence imaging, the penetration of deeper tissues remains a barrier. It is our hope and pursuit that NIR fluorescence imaging technology can achieve good depth and precision in surgery.

Enzyme-induced liquid-to-solid phase transition of mitochondria-targeted AIEgen in cancer theranostics

Enzyme-induced liquid-to-solid phase transition of mitochondria-targeted AIEgen in cancer theranostics

Recent Advances in the Design of Biomedical Materials for Cancer Theranostics

Recent Advances in the Design of Biomedical Materials for Cancer Theranostics

Polydopamine-assisted ion-mediated hyaluronic acid grafting for effective construction of hemocompatible platform with cancer cell recognition.

Surfaces capable of specific biomolecule recognition are essential for cancer theranostics, biosensing, and tissue engineering. However, current grafting methods, critical for dictating the recognition efficiency and biocompatibility of biomaterials, especially hydrophilic polymers, struggle to balance high grafting density with ease of implementation. In pursuit of a simple, effective, and versatile solution, we introduced a polydopamine (PDA)-assisted Ca2+-mediated grafting strategy using hyaluronic acid (HA) as a model material. By increasing the PDA amine group density through deposition time optimization and coiling HA conformation via Ca2+-mediation, the grafting density of aldehyde-bearing HA enhanced 13 folds and reached 2.4 ± 0.2 × 105 chains μm-2. After removement of Ca2+ ions, the dense HA grafting was highly stretched on PDA-coated substrates, close to the contour length of HA. Ca2+-mediated HA (CamHA) grafting was then implemented on versatile substrates with PDA assistance, demonstrating enhanced hemocompatibility by reducing protein adsorption and blood cell interference. Furthermore, the dense and stretched HA chains in CamHA enhanced interactions with CD44, enabling selective recognition of CD44-high cells under static and dynamic conditions. The PDA-assisted CamHA grafting presents a model system for studying the effects of regulated biomaterial grafting on biological functions, offering simplicity, versatility, and the flexibility to select diverse substrates, grafting materials, and targeting elements for customization in a range of biomedical applications.

Isolation of circulating tumor cells: recent progress and future perspectives

AbstractCirculating tumor cells (CTCs) are cancer cells that shed from the primary tumor and enter into body fluids of the patient, where they travel to distant sites and ultimately form metastasis. Understanding the biology of CTCs, in particular at the critical stages of their itinerary, holds promises for better cancer cure. Since the beginning of this century, liquid biopsy has steadily grown to be a keen area of research due to its non-invasive features. As one of the most promising tumor biomarkers, CTCs have shown great potential in cancer diagnosis, prognosis, treatment response monitoring, and the exploration of biological mechanisms. Although various types of isolation and detection technologies emerge constantly, the rarity and heterogeneity of CTCs still pose huge challenges for these methods and make them inefficient. In addition, the clinical practice of different technologies still lacks reasonable and uniform standards. In this review, we provide a detailed overview of the isolation and enrichment strategies of CTCs, as well as their advantages and limitations. By summarizing the current status and suggesting future areas of CTCs research, we hope to continue the concerted effort for pushing forward the clinical application of CTCs, which may represent a paradigm shift for cancer theranostics in the future. Graphical Abstract

Nanoparticles in Cancer Theranostics: Focus on Gliomas

Nanoparticles in Cancer Theranostics: Focus on Gliomas

Peptide Based Engineering of Extracellular Vesicles for Cancer Theranostics and Vaccine

Peptide Based Engineering of Extracellular Vesicles for Cancer Theranostics and Vaccine

Gold nanoparticle encapsulated hybrid MOF: synthesis, characterization, and co-drug delivery of 5-fluorouracil and curcumin

The unique features of Metal–Organic Frameworks (MOFs), including structural flexibility, high surface area, and variable pore size, have drawn attention in cancer therapy. However, despite advances in surface functionalization, engineering structural features, and porosity, achieving controlled release, stability, scalability, and toxicity remains a challenge. The current study reports gold nanoparticle (AuNP) encapsulated dual metal–organic frameworks (MOFs) comprising zeolitic imidazolate (ZIF8) and cobalt-imidazole (ZIF67) by a simple precipitation method for dual drug delivery applications. This combination associates the advantages of AuNPs and MOFs, creating a potent platform for cancer theranostics that combines diagnosis and treatment into one unit. The synthesized composite (AuNPs@ZIF-8/ZIF-67) is functionalized with Folic acid (FA) and loaded with the anticancer agents Curcumin (C) and 5-fluorouracil (5-FU) for co-drug delivery The synthesized composites, namely Au/ZIF8, Au/ZIF8/ZIF67/FA, Au/ZIF8/ZIF67/FA/5-FU, and Au/ZIF8/ZIF67/FA/5-FU/C were characterized using diverse analytical techniques such as FESEM, XRD, FTIR, TEM, and BET. The characterization methods showed that the hybrid MOF structure was stable and intact after AuNP encapsulation and drug loading. The dual MOF composite exhibits a better affinity for loading C and 5-FU with 60% and 40% drug loading capacity, respectively. The simultaneous drug release studies suggest that AuNPs@ZIF-8/ZIF-67 are more responsive to the acidic pH and show a higher cumulative drug release of 5FU and C at the lower value of pH 5. For further validation, the release kinetics data were fitted into the Korsmeyer-Peppas model in the current study. The observed value of n which is less than 0.5 suggests the pseudo-Fickian diffusion mechanism for drug release, demonstrating long-term release of 5FU and C from Au/ZIF8/ZIF67/FA/5-FU/C. The targeted drug delivery system is anticipated to display synergistic therapeutic efficacy from the combined effect of the two anticancer agents and the pH-responsive nature of ZIF systems.

Ultrasound‐Enabled Sonogenetics: Pioneering Advances in Cancer Theranostics

AbstractThe diagnosis and treatment of cancer face significant challenges. Thus, precise and controllable methods for effective tumor management are required. Sonogenetics which combines ultrasound technology with genetic engineering provides a promising solution. This approach utilizes the non‐invasive nature and deep tissue penetration capabilities of ultrasound to enable precise diagnostics and targeted therapies for cancer. This review explores the roles of sonogenetics‐mediated technology in cancer theranostics. The fundamental properties of ultrasound and the mechanisms underlying sonogenetics are first introduced. Then, this work summarizes representative applications of sonogenetics in cancer therapy, including cell‐based therapies, bacteria‐based therapies, and targeted eradication of tumor cells. Additionally, the applications of sonogenetics in cancer diagnosis, focusing on engineered gas vesicles (GVs) and sonogenetics‐mediated in situ generation of GVs for diagnostic purposes are presented. Finally, the challenges and clinical translation potential of sonogenetics are well discussed.

Copper- and Iron-Based Nanoflowers in Cancer Theranostics

In recent years, nanoscience and nanotechnology have gained prominence within materials science, offering new opportunities for cancer diagnosis and treatment. Advances in nanotechnology have allowed for the manipulation and size control of nanomaterials, leading to the development of a wide range of materials. The use of nanomaterials as chemical biology tools in cancer theranostics has been widely investigated, owing to their enhanced stability, biocompatibility, and improved cell permeability. These properties enable precise targeting while addressing the limitations of conventional cancer treatments. Nanoflowers, a specific class of nanomaterials, have recently attracted significant interest due to their promising properties for several biomedical applications. However, despite the growing attention toward nanoflowers, detailed reviews on the subject have been limited. This work focuses on two primary types of hybrid nanoflowers: iron- and copper-based ones. Within this article an overview of recent applications in cancer theranostics are thoroughly reviewed, while the synthesis processes for controlling morphology and size, underlying functions, and their characteristics and uses are also extensively explored, aiming to provide a guide for future developments in the field.

Anionic polysaccharides as delivery carriers for cancer therapy and theranostics: An overview of significance.

Recently, cancer therapy has witnessed remarkable advancements with a growing focus on precision medicine and targeted drug delivery strategies. The application of anionic polysaccharides has gained traction in various drug delivery systems. Anionic polysaccharides have emerged as promising delivery carriers in cancer therapy and theranostics, offering numerous advantages such as biocompatibility, low toxicity, and the ability to encapsulate and deliver therapeutic agents to tumor sites with high specificity. This review underscores the significance of anionic polysaccharides as essential components of the evolving landscape of cancer therapy and theranostics. These polymers can be tailored to carry a wide range of therapeutic cargo, including chemotherapeutic agents, nucleic acids, and imaging agents. Their negative charge enables electrostatic interactions with positively charged drugs and facilitates the formation of stable nanoparticles, liposomes, or hydrogels for controlled drug release. Additionally, their hydrophilic nature aids in prolonging circulation time, reducing drug degradation, and minimizing off-target effects. Besides, some of them could act as targeting agents or therapeutic compounds that lead to improved therapeutic performance. This review offers valuable information for researchers, clinicians, and biomedical engineers. It provides insights into the recent progress in the applications of anionic polysaccharide-based delivery platforms in cancer theranostics to transform patient outcomes.

Heterojunction semiconductor nanocatalysts as cancer theranostics.

Cancer nanotechnology is a promising area of cross-disciplinary research aiming to develop facile, effective, and noninvasive strategies to improve cancer diagnosis and treatment. Catalytic therapy based on exogenous stimulus-responsive semiconductor nanomaterials has shown its potential to address the challenges under the most global medical needs. Semiconductor nanocatalytic therapy is usually triggered by the catalytic action of hot electrons and holes during local redox reactions within the tumor, which represent the response of nontoxic semiconductor nanocatalysts to pertinent internal or external stimuli. However, careful architecture design of semiconductor nanocatalysts has been the major focus since the catalytic efficiency is often limited by facile hot electron/hole recombination. Addressing these challenges is vital for the progress of cancer catalytic therapy. In recent years, diverse strategies have been developed, with heterojunctions emerging as a prominent and extensively explored method. The efficiency of charge separation under exogenous stimulation can be heightened by manipulating the semiconducting performance of materials through heterojunction structures, thereby enhancing catalytic capabilities. This review summarizes the recent applications of exogenous stimulus-responsive semiconducting nanoheterojunctions for cancer theranostics. The first part of the review outlines the construction of different heterojunction types. The next section summarizes recent designs, properties, and catalytic mechanisms of various semiconductor heterojunctions in tumor therapy. The review concludes by discussing the challenges and providing insights into their prospects within this dynamic and continuously evolving field of research.

Research Progress of Hyaluronic Acid-Coated Nanocarriers in Targeted Cancer Therapy.

Background: Hyaluronic acid (HA), as a critical ingredient of extracellular matrix (ECM) and synovial fluid, has attracted extensive attention in targeted tumor thearpy. The superiority of HA is reflected as its great biocompatibility, biodegradability and special binding ability to CD44 receptor. Moreover, CD44 receptor proteins are overexpressed in many kinds of tumor cells and cancer stem cells (CSCs). Therefore, HA is commonly used as ligands for the surface modification of versatile nanocarriers applied in various tumor therapy approaches. Methods: We reviewed a large amount of literature and summarized the unique properties of HA, the rationale for the use of HA as tumor-specific carrier for drug delivery, catabolism of HA coated nanocarriers and research achievements of frequently-used HA-modified organic and inorganic nanocarries. Results: We concluded the significant applications of HA coated nanocarriers in tumor Chemotherapy and chemoresistance, Combination therapy and Cancer theranostics. Conclusion: The application prospect of HA-coated nanocarriers will be more extensive for various targeting combination therapy and theranostics. was concluded so as to provide some potential thoughts for targeted tumor thearpy and even diagnosis.

A multifunctional nanoplatform capable of dual action on tumor PD-L1 for enhanced cancer theranostics

Due to the large amount of PD-L1 on the surface of tumor cells, antibody drugs can only block a small part of PD-L1, limiting the effectiveness of immunotherapy. Here, a MnS nanocluster grafted with dimeric PD-L1 affibody (ZPD-L1) was developed to double act on PD-L1 of tumor cells. ZPD-L1 can specifically target PD-L1 on the surface of tumor cells, and block the interaction between PD-1 and PD-L1 to a certain extent. In acidic tumor microenvironment, MnS nanoclusters can release Mn2+ and H2S. The released Mn2+ can induce reactive oxygen species (ROS) generation through Fenton-like reaction, and serve as magnetic resonance imaging (MRI) contrast agent for effective therapeutic monitoring. H2S can down-regulate PD-L1 expression of tumor cells by amplifying ROS production to inhibit ATP level. Based on ZPD-L1-mediated PD-1/PD-L1 blocking and ROS-induced downregulation of PD-L1 expression, MnS nanoclusters can achieve dual action on tumor PD-L1, amplify immunogenic cell death, maximize the activation of anti-tumor immune response and inhibit tumor growth.

Organelle-Specific Smart Supramolecular Materials for Bioimaging and Theranostics Application.

In cellular environments, certain synthetic molecules can form nanostructures via self-assembly, impacting molecular imaging, and biomedical applications. Control over the formation of these self-assembled nanostructures in subcellular organelle is challenging. By the action of stimuli, either present in the cellular environment or applied externally, in situ generation of molecular precursors can lead to accumulation and supramolecular nanostructure formation, resulting in efficient bioimaging. Here, we summarize smart fluorophore-based ordered nanostructure preparation at specific organelles for efficient bioimaging and therapeutic application towards cancer theranostics. We also present challenges and an outlook regarding intercellular self-assembly for theranostics application. Altogether, smart nanostructured materials with fluorescence read-outs at specific subcellular compartments would be beneficial in synthetic biology and precision therapeutics.

Three Is a Magic Number: Tailored Clickable Chelators Used to Determine Optimal RGD-Peptide Multiplicity in αvβ6-Integrin Targeted 177Lu-Labeled Cancer Theranostics.

The cellular adhesion receptor αvβ6-integrin is highly expressed in many cancers, e.g., pancreatic, lung, head-and-neck, cervical, bladder, and esophageal carcinoma. Multimerization of αvβ6-integrin-specific RGD peptides increases the target affinity and retention but affects biodistribution and pharmacokinetics. Amide formation of the terminal carboxylic acid moieties of the square-symmetrical bifunctional chelator DOTPI with 3-azidopropylamine yields derivatives with 4, 3, and 2 terminal azides and zero, 1, and 2 remaining carboxylic acids, respectively, whereby formation of the 2-cis-isomer is preferred according to NMR investigation of the Eu(III)-complexes. Cu(II)-catalyzed alkyne-azide cycloaddition (CuAAC) of the alkyne-functionalized αvβ6-integrin binding peptide cyclo[YRGDLAYp(NMe)K(pent-4-ynoic amide)] (Tyr2) yields the respective di-, tri-, and tetrameric conjugates for Lu-177-labeling. In mice bearing αvβ6-integrin-expressing xenografts of H2009 (human lung adenocarcinoma) cells, the Lu-177-labeled trimer's tumor-to-blood ratio of 112 exceeds that of the tetramer (10.4) and the dimer (54). Co-infusion of gelofusine (succinylated gelatin) reduces the renal uptake of the trimer by 89%, resulting in a 10-fold better tumor-to-kidney ratio, while no improvement of that ratio is observed with arginine/lysine, para-aminohippuric acid (PAH), and hydroxyethyl starch (HES) coinfusions. Since the Lu-177-labeled Tyr2-trimer outperforms the dimer and the tetramer, such trimers are considered the best lead structures for the ongoing development of αvβ6-integrin targeted anticancer theranostics.

CD133-targeted afatinib nanomicelles for enhanced lung cancer theranostics.

To develop a novel nanomicelle system to target and eradicate CD133-expressing lung cancer stem cells (CSCs) while imaging lung cancer. Averatinib nanomicelles with CD133 aptamers incorporated with gadolinium imaging reagents (M-Afa&Gd-CD133) were synthesized. The anticancer and imaging activities of M-Afa&Gd-CD133 were evaluated both in vitro and in vivo. M-Afa&Gd-CD133 efficiently targeted CD133+ lung CSCs and showed significant antitumor efficacy both in vitro and in vivo. Furthermore, M-Afa&Gd-CD33, as a T1 contrast agent, offers superior and sustained visualization of tumors over an extended period. M-Afa&Gd-CD133 represents a promising strategy for the theranostics of lung cancer.

Advanced Nanoplatform Mediated by CRISPR-Cas9 and Aggregation-Induced Emission Photosensitizers to Boost Cancer Theranostics.

Immunotherapy combined with phototherapy is emerging as a promising strategy to treat omnipotent cancers. In this study, a clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) system, aggregation-induced emission (AIE) photosensitizer (PS) and surface coating of polyethylene imine/hyaluronic acid were combined to construct a multifunctional nanoplatform, denoted as TCPH nanoparticles (NPs), for comprehensive cancer theranostics. TCPH NPs are featured by intrinsic functions including efficient reactive oxygen species (ROS) production, good photothermal conversion, programmed death-ligand 1 (PD-L1)-eliminating capability, and effective intracellular transport. The generated ROS and hyperthermia do not only achieve primary tumor elimination but also regulate the tumor immune microenvironment. Genomic disruption of PD-L1 conspicuously augments its therapeutic efficacy, especially in tumor metastasis and recurrence. Exceptional multimodal imaging navigation has also been developed. Excellent theranostics performance was substantiated in diverse tumor models, implying that this synergistic strategy of phototheranostics and immunotherapy provides a paradigm shift in emerging CRISPR-mediated nanomedicines.