Theranostic Nanosystems Research Articles

Nanomedicine for the Treatment of Lungs Cancer Its Challenges and Future Perspective-A Review

A major public health concern with a global reach,lungs cancer necessitates cutting-edge techniques to treatment. Nanomedicine is a new technology that is currently being used to treat and diagnose lung cancer. This review examines the difficulties in using nano medicine to treat lung cancer and shows the promising directions for this rapidly developing field of study. The issues raised in this review cover a wide range of topics, such as medication delivery, targeted precision, toxicity, and legal obstacles. Approaches based on nanomedicine have the potential to get through these barriers thanks to improvements in drug delivery to lung cancer cell, a decrease in side effects, and increased therapeutic effectiveness. Additionally, this study explores the potential applications of nanomedicine for the treatment of lung cancer, highlighting the significance of cutting-edge technology including personalized medicine techniques,theranostic nanosystems, and targeted nanoparticles. These developments carry the possibility of individualized treatment plans, improved therapeutic results, and reduced side effects. Nanomedicine offers a multifaceted approach to address the challenges of lung cancer treatment, bringing new hope to patients and clinicians alike. By overcoming existing limitations and harnessing the potential of emerging technologies, nano medicine is poised to play a pivotal role in the future of lung cancer therapy. This review serves as a comprehensive overview of the field, shedding light on the path forward in the fight against lung cancer.

Polyamidoamine-Carbon Nanodot Conjugates with Bioreducible Building Blocks: Smart Theranostic Platforms for Targeted siRNA Delivery.

This study focuses on designing hybrid theranostic nanosystems, utilizing gadolinium-doped carbon nanodots decorated with bioreducible amphoteric polyamidoamines (PAAs). The objective is to synergize the exceptional theranostic properties of gadolinium-doped carbon nanodots (CDs) with the siRNA complexation capabilities of PAAs. Linear copolymeric polyamidoamines, based on N,N'-bis(acryloyl)cystamine, arginine, and agmatine, were synthesized, resulting in three distinct amphoteric copolymers. Notably, sulfur bridges within the PAA repeating units confer pronounced susceptibility to glutathione-mediated degradation─a key attribute in the tumor microenvironment. This pathway enables controlled and stimuli-responsive siRNA release, theoretically providing precise spatiotemporal control over therapeutic interventions. The selected PAA, conjugated with CDs using the redox-sensitive spacer cystamine, formed the CDs-Cys-PAA conjugate with superior siRNA complexing capacity. Stable against polyanion exchange, the CDs-Cys-PAA/siRNA complex released siRNA in the presence of GSH. In vitro studies assessed cytocompatibility, internalization, and gene silencing efficacy on HeLa, MCF-7, and 16HBE cell lines.

Sulfated liposome-based artificial cell membrane glycocalyx nanodecoys for coronavirus inactivation by membrane fusion

As a broad-spectrum antiviral nanoparticle, the cell membrane nanodecoy is a promising strategy for preventing viral infections. However, most of the cell membrane nanodecoys can only catch virus and cannot induce inactivation, which may bring about a considerably high risk of re-infection owing to the possible viral escape from the nanodecoys. To tackle this challenge, sulfated liposomes are employed to mimic the cell membrane glycocalyx for constructing an artificial cell membrane glycocalyx nanodecoy that exhibits excellent anti-coronavirus activity against HCoV-OC43, wild-type SARS-CoV-2, Alpha and Delta variant SARS-CoV-2 pseudovirus. In addition, this nanodecoy, loaded with surface sulfate groups as SARS-CoV-2 receptor arrays, can enhance the antiviral capability to virus inactivation through destroying the virus membrane structure and transfer the spike protein to postfusion conformation. Integrating bio-inspired recognition and inactivation of viruses in a single supramolecular entity, the artificial cell membrane nanodecoy opens a new avenue for the development of theranostic antiviral nanosystems, whose mass production is favored due to the facile engineering of sulfated liposomes.

Folate-conjugated near-infrared fluorescent perfluorocarbon nanoemulsions as theranostics for activated macrophage COX-2 inhibition

Activated macrophages play a critical role in the orchestration of inflammation and inflammatory pain in several chronic diseases. We present here the first perfluorocarbon nanoemulsion (PFC NE) that is designed to preferentially target activated macrophages and can deliver up to three payloads (two fluorescent dyes and a COX-2 inhibitor). Folate receptors are overexpressed on activated macrophages. Therefore, we introduced a folate-PEG-cholesterol conjugate into the formulation. The incorporation of folate conjugate did not require changes in processing parameters and did not change the droplet size or fluorescent properties of the PFC NE. The uptake of folate-conjugated PFC NE was higher in activated macrophages than in resting macrophages. Flow cytometry showed that the uptake of folate-conjugated PFC NE occurred by both phagocytosis and receptor-mediated endocytosis. Furthermore, folate-conjugated PFC NE inhibited the release of proinflammatory cytokines (TNF-α and IL-6) more effectively than nonmodified PFC NE, while drug loading and COX-2 inhibition were comparable. The PFC NEs reported here were successfully produced on multiple scales, from 25 to 200 mL, and by using two distinct processors (microfluidizers: M110S and LM20). Therefore, folate-conjugated PFC NEs are viable anti-inflammatory theranostic nanosystems for macrophage drug delivery and imaging.

Nanoscale MOF–Protein Composites for Theranostics

Nanoscale metal–organic frameworks (nMOFs) have gained increasingly more attention as attractive support materials in the immobilization and delivery of proteins for disease theranostics in recent years owing to their various advantages, such as large specific surface areas, well-ordered pore structures, aperture channel distributions, and ease of functionalization. Here, we present an overview of recent progress in nMOF–protein composites for disease theranostics. First, advantages and construction strategies of nMOF–protein composites as drug carriers are introduced. Then, therapeutic modalities and theranostic nanosystems based on nMOF–protein composites are reviewed. Next, we pay specific attention to their biosafety, biodistribution, and excretion in vivo. Finally, the challenges and limitations of nMOF–protein composites for biomedical applications are discussed, along with future perspectives in the field.

Cancer Bioenergetics and Tumor Microenvironments-Enhancing Chemotherapeutics and Targeting Resistant Niches through Nanosystems.

Cancer is an impending bottleneck in the advanced scientific workflow to achieve diagnostic, prognostic, and therapeutic success. Most cancers are refractory to conventional diagnostic and chemotherapeutics due to their limited targetability, specificity, solubility, and side effects. The inherent ability of each cancer to evolve through various genetic and epigenetic transformations and metabolic reprogramming underlies therapeutic limitations. Though tumor microenvironments (TMEs) are quite well understood in some cancers, each microenvironment differs from the other in internal perturbations and metabolic skew thereby impeding the development of appropriate diagnostics, drugs, vaccines, and therapies. Cancer associated bioenergetics modulations regulate TME, angiogenesis, immune evasion, generation of resistant niches and tumor progression, and a thorough understanding is crucial to the development of metabolic therapies. However, this remains a missing element in cancer theranostics, necessitating the development of modalities that can be adapted for targetability, diagnostics and therapeutics. In this challenging scenario, nanomaterials are modular platforms for understanding TME and achieving successful theranostics. Several nanoscale particles have been successfully researched in animal models, quite a few have reached clinical trials, and some have achieved clinical success. Nanoparticles exhibit an intrinsic capability to interact with diverse biomolecules and modulate their functions. Furthermore, nanoparticles can be functionalized with receptors, modulators, and drugs to facilitate specific targeting with reduced toxicity. This review discusses the current understanding of different theranostic nanosystems, their synthesis, functionalization, and targetability for therapeutic modulation of bioenergetics, and metabolic reprogramming of the cancer microenvironment. We highlight the potential of nanosystems for enhanced chemotherapeutic success emphasizing the questions that remain unanswered.

Fungal β-Glucan-Based Nanotherapeutics: From Fabrication to Application.

Fungal β-glucans are naturally occurring active macromolecules used in food and medicine due to their wide range of biological activities and positive health benefits. Significant research efforts have been devoted over the past decade to producing fungal β-glucan-based nanomaterials and promoting their uses in numerous fields, including biomedicine. Herein, this review offers an up-to-date report on the synthetic strategies of common fungal β-glucan-based nanomaterials and preparation methods such as nanoprecipitation and emulsification. In addition, we highlight current examples of fungal β-glucan-based theranostic nanosystems and their prospective use for drug delivery and treatment in anti-cancer, vaccination, as well as anti-inflammatory treatments. It is anticipated that future advances in polysaccharide chemistry and nanotechnology will aid in the clinical translation of fungal β-glucan-based nanomaterials for the delivery of drugs and the treatment of illnesses.

Multifunctional Carbon-Based Nanoparticles: Theranostic Applications in Cancer Therapy and Diagnosis

Cancer diagnosis and treatment are the most critical challenges in modern medicine. Conventional cancer treatments no longer meet the needs of the health field due to the high rate of mutations and epigenetic factors that have caused drug resistance in tumor cells. Hence, the search for unique methods and factors is quickly expanding. The development of nanotechnology in medicine and the search for a system to integrate treatment and diagnosis to achieve an effective approach to overcome the known limitations of conventional treatment methods have led to the emergence of theranostic nanoparticles and nanosystems based on these nanoparticles. An influential group of these nanoparticles is carbon-based theranostic nanoparticles. These nanoparticles have received significant attention due to their unique properties, such as electrical conductivity, high strength, excellent surface chemistry, and wide range of structural diversity (graphene, nanodiamond, carbon quantum dots, fullerenes, carbon nanotubes, and carbon nanohorns). These nanoparticles were widely used in various fields, such as tissue engineering, drug delivery, imaging, and biosensors. In this review, we discuss in detail the recent features and advances in carbon-based theranostic nanoparticles and the advanced and diverse strategies used to treat diseases with these nanoparticles.

Hierarchical design of intelligent α-MnO2-based theranostics nanoplatform for TME-activated drug delivery and T1-weighted MRI

Intelligent “theranostic” nanoplatforms were synthesized based on porous α-MnO2 nanostructures with various concentrations of Gd3+ doping agent (H-GdxMn1-xO2; x = 0.00–0.12 in steps 0.03). After optimization of the doping agent at x = 0.09, the surface of the nanostructures was covered with the chitosan cross-linked tripolyphosphate (Chi-TPP) to reduce the inherent toxicity of the Gd3+ ion. Then a significant amount of doxorubicin (DOX) was loaded on these porous nanoplatforms. The characteristic features of the tumor microenvironment (TME) such as low pH, high temperature, high level of glutathione (GSH), and overproduced endogenous H2O2 act as the driving force to enhance catalytic destruction of the as-synthesized nanoplatforms. Catalytic demolition of H-GdxMn1-xO2@[email protected] “all in one” nanoplatforms not only cause the targeted delivery of pharmaceutical cargo at TME of cancer tissue but also was used for MRI bioimaging and diagnosis of TME condition. Apart from serving as a TME-activated MRI contrast agent, as-synthesized nanoplatforms also serve as a TME-modulating agent to form molecular O2 and simultaneously attenuated tumor hypoxia. Furthermore, the future directions and challenges in the development of the H-GdxMn1-xO2@[email protected] “all in one” theranostic nanosystems were discussed.

Theranostic magnetic nanoparticles: Synthesis, properties, toxicity, and emerging trends for biomedical applications

Nanotechnology provides a wide range of nanosized devices, termed as nanotheranostics, that are integrated with diagnostic and therapeutic properties for real-time monitoring and treatment of diseases. In order to diagnose and cure diseases at the cellular and molecular level, the theranostic nanomedicine must first be able to circulate throughout the body without being destroyed by the host's immune system. Further, this can be linked to a biological ligand for targeting a specific organ or tissue. Novel non-invasive diagnostic agents, such as magnetic nanoparticles (MNPs), are currently employed in magnetic resonance imaging (MRI). Previously, they have been used for imaging various diseases; but new developments have unlocked the way for targeting the drug to the cellular membrane and multi-modal imaging with MNPs. For the production of MNPs, a wide range of synthetic methods such as physical and thermal degradation, hydrothermal production, microemulsion, co-precipitation, and polyol processes have been used, which include few examples of biosynthetic techniques. One of the biggest concern with MNPs is that they have potential toxicity issues in biomedical applications. Due to their reactive surface features and their capacity to penetrate the cell and tissue membranes, MNPs can elicit a powerful cytotoxic effect and hyperthermia. Numerous laboratories have studied in vitro cellular toxicity of MNPs in a wide variety of cancer and normal cell lines, and their findings established the fact that at low concentrations, MNPs are nontoxic, and at high concentrations, they have marginal toxicity, demonstrating their biocompatibility and acceptable safety profile. Diagnostic imaging using nanosystems can be performed using the aforementioned approaches, including MRI, optical imaging, nuclear imaging, computed tomography, ultrasound etc. In this article, various theranostic magnetic nanosystems are discussed in the context of their manufacturing and development for therapeutic and diagnostic use, focusing mainly on in vitro and in vivo applications. Further emphasis on their potential for integrating other nanostructures with current biotechnology, as well as the special qualities of magnetic nanosystems are further highlighted to explain the future role of magnetic nanosystems in the successful therapy.

Multimodality: phantom imaging for superparamagnetic graphene composites using green technology for theranostic nanosystems

Multimodality: phantom imaging for superparamagnetic graphene composites using green technology for theranostic nanosystems

Recent Trends and Developments in Multifunctional Nanoparticles for Cancer Theranostics.

Conventional anticancer treatments, such as radiotherapy and chemotherapy, have significantly improved cancer therapy. Nevertheless, the existing traditional anticancer treatments have been reported to cause serious side effects and resistance to cancer and even to severely affect the quality of life of cancer survivors, which indicates the utmost urgency to develop effective and safe anticancer treatments. As the primary focus of cancer nanotheranostics, nanomaterials with unique surface chemistry and shape have been investigated for integrating cancer diagnostics with treatment techniques, including guiding a prompt diagnosis, precise imaging, treatment with an effective dose, and real-time supervision of therapeutic efficacy. Several theranostic nanosystems have been explored for cancer diagnosis and treatment in the past decade. However, metal-based nanotheranostics continue to be the most common types of nonentities. Consequently, the present review covers the physical characteristics of effective metallic, functionalized, and hybrid nanotheranostic systems. The scope of coverage also includes the clinical advantages and limitations of cancer nanotheranostics. In light of these viewpoints, future research directions exploring the robustness and clinical viability of cancer nanotheranostics through various strategies to enhance the biocompatibility of theranostic nanoparticles are summarised.

Stimuli-responsive hybrid nanoconstructs for efficient theranostic applications in nanomedicine

Stimuli-responsive hybrid nanoconstructs for efficient theranostic applications in nanomedicine The multidisciplinary ERC Starting Grant project “Hybrid immune-eluding nanocrystals as smart and active theranostic weapons against cancer” (TrojaNanoHorse) and the following ERC Proof-of-Concept Grant aim to develop a new generation of multifunctional theranostic nanosystems and apply them for improved cancer treatment, efficient cell imaging and for providing high safety for the hosting organism.

Advancements in redox-sensitive micelles as nanotheranostics: A new horizon in cancer management.

World Health Organisation (WHO) delineated cancer as one of the foremost reasons for mortality with 10 million deaths in the year 2020. Early diagnosis and effective drug delivery are of utmost importance in cancer management. The entrapment of both bio-imaging dyes and drugs will open novel avenues in the area of tumor theranostics. Elevated levels of reactive oxygen species (ROS) and glutathione (GSH) are the characteristic features of the tumor microenvironment (TME). Researchers have taken advantage of these specific TME features in recent years to develop micelle-based theranostic nanosystems. This review focuses on the advantages of redox-sensitive micelles (RSMs) and supramolecular self-assemblies for tumor theranostics. Key chemical linkers employed for the tumor-specific release of the cargo have been discussed. In vitro characterisation techniques used for the characterization of RSMs have been deliberated. Potential bottlenecks that may present themselves in the bench-to-bedside translation of this technology and the regulatory considerations have been deliberated.

Intracellular miRNA-Triggered Surface-Enhanced Raman Scattering Imaging and Dual Gene-Silencing Therapy of Cancer Cell.

Development of theranostic nanosystems integrating cascaded surface-enhanced Raman scattering (SERS) imaging and gene silencing therapy for accurate cancer diagnosis and treatment is still a big challenge and rarely reported. Herein, a novel Au nanoparticles (AuNPs)-based theranostic nanosystem containing AuNP-Ys and AuNP-Ds for highly sensitive and specific cancer diagnosis and treatment was proposed for cascaded SERS imaging of intracellular cancer-related miR-106a and miR-106a-triggered DNAzyme-based dual gene-silencing therapy of cancer cells. The AuNP-Ys were prepared by modifying the AuNPs with specially designed Y-motifs, and the AuNP-Ds were obtained by colabeling Raman molecules and dsDNA linkers on AuNPs. When identifying the intracellular cancer-related miRNAs, the Y-motifs and dsDNA linkers undergoes miRNA-triggered ATP-driven conformational transitions and releases the miRNA for recycling, which results in the formation of AuNP network nanostructures to generate significantly enhanced SERS signals for sensitive identification of the cancer cells as well as the amplification and specific activation of DNAzymes to catalyze the Mg2+-assisted cleavage of the Survivin and c-Jun mRNAs for effective dual gene-silencing therapy of cancer cells. The AuNP-based theranostic nanosystem achieves the synergism of target-triggered SERS imaging and DNAzyme-based dual gene-silencing therapy with enhanced specificity, sensitivity, and curative effect, which can be a powerful tool for accurate diagnosis and efficient treatment of cancers.

Stimuli-responsive theranostic system: A promising approach for augmented multimodal imaging and efficient drug release

Destruction of drug resistant and invisible micro-tumors requires innovative screening and treatment modalities. Theranostic nanosystems offering multimodal imaging and therapy are attractive platforms with potential to make micro-tumors visible to clinicians. Gold nanoparticles (AuNPs) are intrinsic theranostic agents and act as fluorescence quenchers. They can be easily transformed to multimodal imaging and combination therapy agents by combining them with various adjuvant therapies such as photodynamic therapy. In this study, we developed a highly specific, hybrid theranostic agent that is only activated when it meets with its stimuli at the site of interest. Surface-coated AuNPs were modified with Cathepsin B cleavable peptide (stimuli responsive linker) and Verteporfin (photosensitizer and fluorescence imaging agent). Unless the theranostic system meets with the internal stimuli in tumor cells, fluorescence is quenched due to AuNP-Verteporfin and Verteporfin-Verteporfin interactions. Following cellular internalization of the theranostic agent, fluorescence is gained by Cathepsin B cleavage and phototoxicity is initiated by light. The system was efficiently internalized by SKOV-3 cells and demonstrated high specificity towards its stimuli. In comparison to Verteporfin, ∼14-fold fluorescence increase, 81% fluorescence recovery and comparable toxicity were achieved. The system is a promising candidate for multimodal imaging and dual treatment to destroy the micro-tumors.

Tumor-Microenvironment-Activated NIR-II Nanotheranostic Platform for Precise Diagnosis and Treatment of Colon Cancer.

Rational design of tumor-microenvironment (TME)-activated nanoformulation for precisely targeted cancer treatment has recently attracted an enormous attention. However, the all-in-one TME-activated theranostic nanosystems with a simple preparation and high biocompatibility are still rarely reported. Herein, catalase nanocrystals (CatCry) are first introduced as a tumor microenvironment activatable nanoplatform for selective theranostics of colon cancer. They are engaged as (i) a "nanoreactor" for silver nanoparticles (AgNP) synthesis, (ii) a nanovehicle for tumor delivery of anticancer drug doxorubicin (DOX), and (iii) an in situ O2 generator to relief tumor hypoxia. When CatCry-AgNP-DOX nanoformulation is within a tumor, the intratumoral H2S turns AgNP into Ag2S nanoparticles, inducing a photothermal effect and NIR-II emission under 808 nm laser irradiation and also triggering DOX release. Simultaneously, CatCry catalyzes intratumoral H2O2 into O2, relieving hypoxia and enhancing chemotherapy. In contrast, when delivered to healthy tissue without increased concentration of H2S, the developed nanoformulation remains in the "off" state and no theranostic action takes place. Studies with colon cancer cells in vitro and a murine colon cancer model in vivo demonstrated that CatCry-AgNP-DOX delivered a synergistic combination of PTT and enhanced chemotherapy, enabling complete eradication of tumor with minimal side effects. This work not only introduces nanoplatform for theranostics of H2S-rich tumors but also suggests a general strategy for protein-crystal-based nanomedicine.

A Reduction Active Theranostic Nanoparticle for Enhanced Near-Infrared Imaging and Phototherapy by Reducing Glutathione Level in Cancer Cells.

Facile preparation of a tumoral-stimuli-activated theranostic nanoparticle with simple constituents remains a challenge for tumor theranostic nanosystems. Herein we design a simple reductionresponsive turn-on theranostic nanoparticle for achieving fluorescent imaging and phototherapy combination. The theranostic nanoparticle is prepared by a simple one-step dialysis method of reduction active amphiphilic hyperbranched poly(β-amidoamines) and a near-infrared (NIR) dye indocyanine green (ICG). The fluorescence of ICG is quenched by the aggregation-caused quenching (ACQ) effect. The fluorescent intensity of free ICG at 816 nm was ∼40 times as high as that of particulate ICG. After reductive nanoparticles incubated with dithiothreitol (DTT), the size of the nanoparticles increased from 160 nm to 610 nm by Dynamic light scattering (DLS). As nanoparticles were internalized by cancer cells, the disulfide bonds would be cleaved by intracellular reduction agents like glutathione (GSH), leading to the release of entrapped ICG. The released ICG regained its fluorescence for self-monitoring the release and therapeutic effect of ICG by fluorescence spectra and the quantitative evaluation of NIR fluorescence intensity. Remarkably, nanoparticles can also reinforce antitumor efficacy through photodynamic therapy and GSH depletion property. This study provides new insights into designing turn-on theranostic systems.

All-in-One Nanomedicine: Multifunctional Single-Component Nanoparticles for Cancer Theranostics.

The development of cancer diagnostic imaging and treatment is a major concern worldwide. By integrating imaging and therapy into one theranostic nanoplatform for simultaneously detecting tumors, evaluating the targeting ability and timely monitoring therapeutic responses provide more opportunities for precision medicine. Among various theranostic nanosystems, a series of single-component nanoparticles (NPs) have been developed for "all-in-one" theranostics, which presents the unique properties of facile preparation, simple composition, defined structure, high reproducibility, and excellent biocompatibility. Specifically, utilizing single-component NPs for both diagnostics and therapeutics can reduce the possible numerous untoward side effects and risks to the living body. In this review, the recent progress of multifunctional single-component NPs in the applications of cancer theranostics is systematically summarized. Notably, the structure design, categories of NPs, targeted strategies, biomedical applications, potential barriers, challenges, and prospects for the future clinical practice of this rapidly growing field are discussed.

Targeted and activatable nanosystem for fluorescent and optoacoustic imaging of immune-mediated inflammatory diseases and therapy via inhibiting NF-κB/NLRP3 pathways

Immune-mediated inflammatory diseases (IMIDs) represent a diverse group of diseases and challenges remain for the current medications. Herein, we present an activatable and targeted nanosystem for detecting and imaging IMIDs foci and treating them through blocking NF-κB/NLRP3 pathways. A ROS-activatable prodrug BH-EGCG is synthesized by coupling a near-infrared chromophore with the NF-κB/NLRP3 inhibitor epigallocatechin-3-gallate (EGCG) through boronate bond which serves as both the fluorescence quencher and ROS-responsive moiety. BH-EGCG molecules readily form stable nanoparticles in aqueous medium, which are then coated with macrophage membrane to ensure the actively-targeting capability toward inflammation sites. Additionally, an antioxidant precursor N-acetylcysteine is co-encapsulated into the coated nanoparticles to afford the nanosystem BH-EGCG&NAC@MM to further improve the anti-inflammatory efficacy. Benefiting from the inflammation-homing effect of the macrophage membrane, the nanosystem delivers payloads (diagnostic probe and therapeutic drugs) to inflammatory lesions more efficiently and releases a chromophore and two drugs upon being triggered by the overexpressed in-situ ROS, thus exhibiting better theranostic performance in the autoimmune hepatitis and hind paw edema mouse models, including more salient imaging signals and better therapeutic efficacy via inhibiting NF-κB pathway and suppressing NLRP3 inflammasome activation. This work may provide perceptions for designing other actively-targeting theranostic nanosystems for various inflammatory diseases.