Recent advances in AIE-based platforms for cancer immunotherapy.

Aggregation-induced emission luminogens (AIEgens) possess the unique property of enhanced fluorescence and photostability in aggregated states, making them exceptional materials for the convergence of imaging and phototherapy. With their inherent advantages, AIEgens are propelling the field of nanomedicine into a vibrant frontier in the phototheranostics of a spectrum of diseases, particularly in the realm of cancer immunotherapy. AIEgens-based therapeutics enhance the cancer immune response through a variety of approaches, including real-time image-guided precise therapy, induction of programmed cell death, metabolic reprogramming, and modulation of the tumor microenvironment. Additionally, they contribute to the synergistic effect of immune checkpoint inhibition, a pivotal aspect of modern cancer immunotherapy strategies. This review offers a comprehensive overview of the integration of AIEgens in nanomedicine and their role in immune adaptation, highlighting the advantages, basic action mechanisms, and recent advancement of AIEgens as promising therapeutic platform for cancer immunotherapy.

Biomimetic Cell Membrane-Coated Nanoparticles for Cancer Theranostics.

Nanoparticles can enhance drugs accumulating at the tumor site and hold tremendous promise for achieving effective tumor treatment. However, due to the complexity of cancer heterogeneity and suppressive tumor microenvironment, the delivery of traditional nanoparticles has poor infiltration and off-target effects, making it difficult to control the drug release rate and causing off-target toxicity. In recent years, cell membrane-coated biomimetic nanoparticles have been developed, which have both the natural characteristics of biomembranes and the physical characteristics of traditional nanoparticles, thus improving the homologous targeting ability of nanoparticles to tumor cells and better biocompatibility. In this paper, we reviewed the application of single cell membrane and hybrid cell membrane-coated biomimetic nanoparticles in the integration for tumor diagnosis and treatment. We talked about the preparation methods of cell membrane-coated nanoparticles, the targeting mechanisms, and the effects of imaging and therapeutic outcomes of different cell membrane-coated biomimetic nanoparticles in detail. Finally, we discussed the existing problems and prospects of cell membrane-coated biomimetic nanomaterials.

Unlocking lysosomal acidity to activate membranolytic module for accurately cancer theranostics.

Chemotherapy drug efflux, toxic side effects, and low efficacy against drug-resistant cells have plagued safe and efficient cancer theranostics. However, the materials or methods that resolve these defects all-in-one are scarce. Here, a new cancer theranostics strategy is proposed by utilizing changes in lysosomal acidity in cancer cells to activate the membranolytic model to overcome these obstacles together. Therefore, a simple fluorescent anthracene derivative Lyso-Mito is developed, which has a perfect pKa (4.62) value that falls between the pH of lysosomes in cancer and normal cells. Lyso-Mito itself can precisely target and convert the pH perturbation of lysosomes in cancer cells to fluorescent response and membranolytic module activity to accomplish the low drug efflux, weak toxic side effects, and low drug-resistant cancer diagnosis and treatment without linking other functional units or any additional assistance. Hereby, a new cancer theranostics strategy of integrating organelle microenvironment and the membranolytic model is realized.

Quantum Dots Functionalized Polymeric Nanoparticles as Cancer Theranostics: An Advanced Nanomedicine Strategy.

BACKGROUND: Cancer is a life-threatening disease prevalent worldwide, but its proper treatment has not yet been developed. Conventional therapies, like chemotherapy, sur-gery, and radiation, have shown relapse and drug resistance. Nanomedicine comprising cancer theranostics based on imaging probes functionalized with polymeric nanoconjugates is acquir-ing importance due to its targeting capability, biodegradability, biocompatibility, capacity for drug loading, and long blood circulation time. The application of synthetic polymers contain-ing anti-cancer agents and functionalizing their surface amenities with diagnostic probes offer a nano-combinatorial model in cancer theranostics. OBJECTIVE: This study aimed to highlight the recent advancements in quantum dots-functionalized nanoconjugates and substantial progress in advanced polymeric nanomaterials in cancer theragnostics. METHODS: This review details the synthetic methods for fabricating Quantum Dots (QDs) and QDs-functionalized polymeric nanoparticles, such as the hydrothermal method, solvothermal technique, atomic layer desorption, electrochemical method, microwave, and ultrasonic method. RESULTS: Conjugating nanoparticles with photo-emitting quantum dots has shown efficacy for real-time monitoring and treating multi-drug-resistant cancer. CONCLUSION: Quantum dots are used in phototherapy, bioimaging, and medication delivery for cancer therapy. Real-time monitoring of therapy is possible and multiple models of hybridized quantum dots may be created to treat cancer. This review has discovered that numerous at-tempts have been made to conjugate carbon and graphene-based quantum dots with various biomolecules.

Neutrophil-Targeting Semiconducting Polymer Nanotheranostics for NIR-II Fluorescence Imaging-Guided Photothermal-NO-Immunotherapy of Orthotopic Glioblastoma.

Glioblastoma (GBM) is one of the deadliest primary brain tumors, but its diagnosis and curative therapy still remain a big challenge. Herein, neutrophil-targeting semiconducting polymer nanotheranostics (SSPNiNO) is reported for second near-infrared (NIR-II) fluorescence imaging-guided trimodal therapy of orthotopic glioblastoma in mouse models. The SSPNiNO are formed based on two semiconducting polymers acting as NIR-II fluorescence probe as well as photothermal conversion agent, respectively. A thermal-responsive nitric oxide (NO) donor and an adenosine 2A receptor (A2AR) inhibitor are co-integrated into SSPNiNO to enable trimodal therapeutic actions. SSPNiNO are surface attached with a neutrophil-targeting ligand to mediate their effective delivery into orthotopic GBM sites via a "Trojan Horse" manner, enabling high-sensitive NIR-II fluorescence imaging. Upon NIR-II light illumination, SSPNiNO effectively generates heat via NIR-II photothermal effect, which not only kills tumor cells and induces immunogenic cell death (ICD), but also triggers controlled NO release to strengthen tumor ICD. Additionally, the encapsulated A2AR inhibitor can modulate immunosuppressive tumor microenvironment by blocking adenosine-A2AR pathway, which further boosts the antitumor immunological effect to observably suppress the orthotopic GBM progression. This study can provide a multifunctional theranostic nanoplatform with cumulative therapeutic actions for NIR-II fluorescence imaging-guided effective GBM treatment.

Recent Advances in Pretargeted Strategy for Cancer Theranostics.

In nuclear medicine, theranostic probes that combine nuclear imaging capabilities with therapeutic functions have shown promise for the diagnosis and treatment of cancers. Nevertheless, the development of theranostic probes may be constrained by two principal factors: (1) the discrepancy between the slow accumulation time of the probes in the tumours and the short-lived radionuclides, and (2) the suboptimal imaging/treatment effect and high radioactive toxicity caused by long-lived radionuclides. In recent years, pretargeted strategy has been proposed as a potential solution to solve these problems. In the pretargeted strategy, two components consisting of a tumour-targeting vector (e.g., antibody) and a radionuclide are injected separately, which can then couple in the tumour tissues to trap radionuclides for nuclear imaging and/or therapy. This two-step process allows for the independent optimization of the pharmacokinetics of them in vivo, benefiting to improve nuclear imaging and/or therapy of tumours in vivo. In this concept, we will discuss the principle of the pretargeted strategy, with a focus on the discussion of different tumour-targeting vectors, including antibody-mediated delivery, nanoparticle-mediated delivery, metabolic glycan labeling-mediated accumulation, and enzyme-triggered in situ self-assembly-mediated retention. Finally, we will discuss the current challenges and perspectives on their applications for cancer theranostics in clinics.

Harnessing Dual Phototherapy and Immune Activation for Cancer Treatment: The Development and Application of BODIPY@F127 Nanoparticles.

Conventional phototherapeutic agents are typically used in either photodynamic therapy (PDT) or photothermal therapy (PTT). However, efficacy is often hindered by hypoxia and elevated levels of heat shock proteins in the tumor microenvironment (TME). To address these limitations, a formylated, near-infrared (NIR)-absorbing and heavy-atom-free Aza-BODIPY dye is presented that exhibits both type-I and type-II PDT actions with a high yield of reactive oxygen species (ROS) and manifests efficient photothermal conversion by precise adjustments to the conjugate structure and electron distribution, leading to a large amount of ROS production even under severe hypoxia. To improve biosafety and water solubility, the dye with an amphiphilic triblock copolymer (Pluronic F-127), yielding BDP-6@F127 nanoparticles (NPs) is coated. Furthermore, inspired by the fact that phototherapy triggers the release of tumor-associated antigens, a strategy that leverages potential immune activation by combining PDT/PTT with immune checkpoint blockade (ICB) therapy to amplify the systemic immune response and achieve the much-desired abscopal effect is developed. In conclusion, this study presents a promising molecular design strategy that integrates multimodal therapeutics for a precise and effective approach to cancer therapy.

Targeted Radionuclide Therapy in Glioblastoma.

Despite the development of various novel therapies, glioblastoma (GBM) remains a devastating disease, with a median survival of less than 15 months. Recently, targeted radionuclide therapy has shown significant progress in treating solid tumors, with the approval of Lutathera for neuroendocrine tumors and Pluvicto for prostate cancer by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). This achievement has shed light on the potential of targeted radionuclide therapy for other solid tumors, including GBM. This review presents the current status of targeted radionuclide therapy in GBM, highlighting the commonly used therapeutic radionuclides emitting alpha, beta particles, and Auger electrons that could induce potent molecular and cellular damage to treat GBM. We then explore a range of targeting vectors, including small molecules, peptides, and antibodies, which selectively target antigen-expressing tumor cells with minimal or no binding to healthy tissues. Considering that radiopharmaceuticals for GBM are often administered locoregionally to bypass the blood-brain barrier (BBB), we review prominent delivery methods such as convection-enhanced delivery, local implantation, and stereotactic injections. Finally, we address the challenges of this therapeutic approach for GBM and propose potential solutions.

A recent insight of applications of gold nanoparticles in glioblastoma multiforme therapy.

The application of gold nanoparticles (AuNPs) in cancer therapy, particularly targeted therapy of glioblastoma multiforme (GBM), is an up-and-coming field of research that has gained much interest in recent years. GBM is a life-threatening malignant tumour of the brain that currently has a 95 % death rate with an average of 15 months of survival. AuNPs have proven to have wide clinical implications and compelling therapeutic potential in many researches, specifically in GBM treatment. It was found that the reason why AuNPs were highly desired for GBM treatment was due to their unique properties that diversified the applications of AuNPs further to include imaging, diagnosis, and photothermal therapy. These properties include easy synthesis, biocompatibility, and surface functionalization. Various studies also underscored the ability of AuNPs to cross the blood-brain-barrier and selectively target tumour cells while displaying no major safety concerns which resulted in better therapy results. We attempt to bring together some of these studies in this review and provide a comprehensive overview of safety evaluations and current and potential applications of AuNPs in GBM therapy that may result in AuNP-mediated therapy to be the new gold standard for GBM treatment.

Hybrid Nanoparticles for Cancer Theranostics: A Critical Review on Design, Synthesis, and Multifunctional Capabilities.

Theranostics, a method that combines targeted therapy and diagnostic imaging, has emerged as a viable route for enhancing cancer treatment, and hybrid nanoparticles (HNPs) are at the forefront of this field. Metallic, polymeric, lipid-based, and silica- based HNPs are studied for targeting and biocompatibility. Using HNPs, chemotherapeutic drugs, small interfering RNA, and therapeutic genes can be given precisely and controlled. This enhances therapeutic efficacy and reduces adverse effects. With fluorescence dyes, MRI contrast agents, and PET tracers, real-time therapy response monitoring is conceivable. A nano platform with therapeutic and diagnostic capabilities holds great promise for personalized medicine and precision oncology. The present study discusses HNPs' biocompatibility, stability, immunogenicity, and long-term biosafety, which are crucial to the clinical translation of cancer theranostics. Further, in this in- -depth investigation, we investigated the design, synthesis, and multifunctional activities of HNPs for use in cancer theranostics.

Advances in nanobubbles for cancer theranostics: Delivery, imaging and therapy.

Maximizing treatment efficacy and forecasting patient prognosis in cancer necessitates the strategic use of targeted therapy, coupled with the prompt precise detection of malignant tumors. Theutilizationof gaseous systems as an adaptable platform for creating nanobubbles (NBs) has garnered significant attention as theranostics, which involve combining contrast chemicals typically used for imaging with pharmaceuticals to diagnose and treattumorssynergistically in apersonalizedmanner for each patient. This review specifically examines the utilization of oxygen NBsplatforms as a theranostic weapon in the field of oncology. We thoroughly examine the key factors that impact the effectiveness of NBs preparations and the consequences of these treatment methods. This review extensively examines recent advancements in composition schemes, advanced developments in pre-clinical phases, and other groundbreaking inventions in the area of NBs. Moreover, this review offers a thorough examination of the optimistic future possibilities, addressing prospective methods for improvement and incorporation into widely accepted therapeutic practices. As we explore the ever-changing field of cancer theranostics, the incorporation of oxygen NBs appears as a promising development, providing new opportunities for precision medicine and marking a revolutionary age in cancer research and therapy.

Smart Multifunctional Nanoparticles in Cancer Theranostics: Progress and Prospect.

BACKGROUND: Worldwide, cancer is the second most common cause of death. Chemotherapy and other traditional cancer treatments have toxicities that affect normal cells in addition to their intended targets, necessitating the development of novel approaches to enhance cell-specific targeting. METHODS: The present work summarizes the scientific information on nanoparticles in cancer theranostics to provide a comprehensive insight into the preventive and therapeutic potential of nanoparticles in cancer. Scopus, PubMed, Science Direct, and Google Scholar databases are searched to collect all the recent (2015-2023) scientific information on smart multifunctional nanoparticles using the terms nanotechnology, cancer theranostics, and polymer. RESULTS: The use of nanomaterials as chemical biology tools in cancer theranostics has been thoroughly investigated. They demonstrate expanded uses in terms of stability, biocompatibility, and enhanced cell permeability, enabling precision targeting and ameliorating the drawbacks of conventional cancer treatments. The nano platform presents a fascinating chance to acquire multifunctionality and targeting techniques. The production of smart nanomaterials, specifically with regard to the advent of nanotechnology, has revolutionized the diagnosis and treatment of cancer. The capability of nanoparticles to functionalize with a variety of biosubstrates, including aptamers, antibodies, DNA, and RNA, and their broad surface area allow them to encapsulate a huge number of molecules, contributing to their theranostic effect. Comparatively speaking, economical, easily produced, and less toxic nanomaterials formed from biological sources are thought to have benefits over those made using conventional processes. CONCLUSION: The present study highlights the uses of several nanoparticles (NPs), and describes numerous cancer theranostics methodologies. The benefits and difficulties preventing their adoption in cancer treatment and diagnostic applications are also critically reviewed. The use of smart nanomaterials, according to this review's findings, can considerably advance cancer theranostics and open up new avenues for tumor detection and treatment.

Glycosylated nanoplatforms: From glycosylation strategies to implications and opportunities for cancer theranostics.

Glycosylated nanoplatforms have emerged as promising tools in the field of cancer theranostics, integrating both therapeutic and diagnostic functionalities. These nanoscale platforms are composed of different materials such as lipids, polymers, carbons, and metals that can be modified with glycosyl moieties to enhance their targeting capabilities towards cancer cells. This review provides an overview of different modification strategies employed to introduce glycosylation onto nanoplatforms, including chemical conjugation, enzymatic methods, and bio-orthogonal reactions. Furthermore, the potential applications of glycosylated nanoplatforms in cancer theranostics are discussed, focusing on their roles in drug delivery, imaging, and combination therapy. The ability of these nanoplatforms to selectively target cancer cells through specific interactions with overexpressed glycan receptors is highlighted, emphasizing their potential for enhancing efficacy and reducing the side effects compared to conventional therapies. In addition, the incorporation of diagnostic components onto the glycosylated nanoplatforms provided the capability of simultaneous imaging and therapy and facilitated the real-time monitoring of treatment response. Finally, challenges and future perspectives in the development and translation of glycosylated nanoplatforms for clinical applications are addressed, including scalability, biocompatibility, and regulatory considerations. Overall, this review underscores the significant progress made in the field of glycosylated nanoplatforms and their potential to revolutionize cancer theranostics.

AS1411 aptamer/RGD dual functionalized theranostic chitosan-PLGA nanoparticles for brain cancer treatment and imaging.

Conventional chemotherapy and poor targeted delivery in brain cancer resulting to poor treatment and develop resistance to anticancer drugs. Meanwhile, it is quite challenging to diagnose/detection of brain tumor at early stage of cancer which resulting in severity of the disease. Despite extensive research, effective treatment with real-time imaging still remains completely unavailable, yet. In this study, two brain cancer cell specific moieties i.e., AS1411 aptamer and RGD are decorated on the surface of chitosan-PLGA nanoparticles to improve targeted co-delivery of docetaxel (DTX) and upconversion nanoparticles (UCNP) for effective brain tumor therapy and real-time imaging. The nanoparticles were developed by a slightly modified emulsion/solvent evaporation method. This investigation also translates the successful synthesis of TPGS-chitosan, TPGS-RGD and TPGS-AS1411 aptamer conjugates for making PLGA nanoparticle as a potential tool of the targeted co-delivery of DTX and UCNP to the brain cancer cells. The developed nanoparticles have shown an average particle size <200 nm, spherical in shape, high encapsulation of DTX and UCNP in the core of nanoparticles, and sustained release of DTX up to 72 h in phosphate buffer saline (pH 7.4). AS1411 aptamer and RGD functionalized theranostic chitosan-PLGA nanoparticles containing DTX and UCNP (DUCPN-RGD-AS1411) have achieved greater cellular uptake, 89-fold improved cytotoxicity, enhanced cancer cell arrest even at lower drug conc., improved bioavailability with higher mean residence time of DTX in systemic circulation and brain tissues. Moreover, DUCPN-RGD-AS1411 have greatly facilitated cellular internalization and higher accumulation of UCNP in brain tissues. Additionally, DUCPN-RGD-AS1411 demonstrated a significant suppression in tumor growth in brain-tumor bearing xenograft BALB/c nude mice with no impressive sign of toxicities. DUCPN-RGD-AS1411 has great potential to be utilized as an effective and safe theranostic tool for brain cancer and other life-threatening cancer therapies.

Dual-Responsive Supramolecular Polymeric Nanomedicine for Self-Cascade Amplified Cancer Immunotherapy.

Insufficient tumor immunogenicity and immune escape from tumors remain common problems in all tumor immunotherapies. Recent studies have shown that pyroptosis, a form of programmed cell death that is accompanied by immune checkpoint inhibitors, can induce effective immunogenic cell death and long-term immune activation. Therapeutic strategies to jointly induce pyroptosis and reverse immunosuppressive tumor microenvironments are promising for cancer immunotherapy. In this regard, a dual-responsive supramolecular polymeric nanomedicine (NCSNPs) to self-cascade amplify the benefits of cancer immunotherapy is designed. The NCSNPs are formulated by ß-cyclodextrin coupling nitric oxide (NO) donor, a pyroptosis activator, and NLG919, an indoleamine 2,3-dioxygenase (IDO) inhibitor, and self-assembled through host-guest molecular recognition and hydrophobic interaction to obtain nanoparticles. NCSNPs possess excellent tumor accumulation and bioavailability attributed to ingenious supramolecular engineering. The study not only confirms the occurrence of NO-triggered pyroptosis in tumors for the first time but also reverses the immunosuppressive microenvironment in tumor sites via an IDO inhibitor by enhancing the infiltration of cytotoxic T lymphocytes, to achieve remarkable inhibition of tumor proliferation. Thus, this study provides a novel strategy for cancer immunotherapy.

Transforming native exosomes to engineered drug vehicles: A smart solution to modern cancer theranostics.

Exosomes have been the hidden treasure of the cell in terms of cellular interactions, transportation and therapy. The native exosomes (NEx) secreted by the parent cells hold promising aspects in cancer diagnosis and therapy. NEx has low immunogenicity, high biocompatibility, low toxicity and high stability which enables them to be an ideal prognostic biomarker in cancer diagnosis. However, due to heterogeneity, NEx lacks specificity and accuracy to be used as therapeutic drug delivery vehicle in cancer therapy. Transforming these NEx with their innate structure and multiple receptors to engineered exosomes (EEx) can provide better opportunities in the field of cancer theranostics. The surface of the NEx exhibits numeric receptors which can be modified to pave the direction of its therapeutic drug delivery in cancer therapy. Through surface membrane, EEx can be modified with increased drug loading potentiality and higher target specificity to act as a therapeutic nanocarrier for drug delivery. This review provides insights into promising aspects of NEx as a prognostic biomarker and drug delivery tool along with its need for the transformation to EEx in cancer theranostics. We have also highlighted different methods associated with NEx transformations, their nano-bio interaction with recipient cells and major challenges of EEx for clinical application in cancer theranostics.

Therapeutic and diagnostic applications of carbon nanotubes in cancer: recent advances and challenges.

Carbon nanotubes (CNTs) are allotropes of carbon, composed of carbon atoms forming a tube-like structure. Their high surface area, chemical stability, and rich electronic polyaromatic structure facilitate their drug-carrying capacity. Therefore, CNTs have been intensively explored for several biomedical applications, including as a potential treatment option for cancer. By incorporating smart fabrication strategies, CNTs can be designed to specifically target cancer cells. This targeted drug delivery approach not only maximizes the therapeutic utility of CNTs but also minimizes any potential side effects of free drug molecules. CNTs can also be utilised for photothermal therapy (PTT) which uses photosensitizers to generate reactive oxygen species (ROS) to kill cancer cells, and in immunotherapeutic applications. Regarding the latter, for example, CNT-based formulations can preferentially target intra-tumoural regulatory T-cells. CNTs also act as efficient antigen presenters. With their capabilities for photoacoustic, fluorescent and Raman imaging, CNTs are excellent diagnostic tools as well. Further, metallic nanoparticles, such as gold or silver nanoparticles, are combined with CNTs to create nanobiosensors to measure biological reactions. This review focuses on current knowledge about the theranostic potential of CNT, challenges associated with their large-scale production, their possible side effects and important parameters to consider when exploring their clinical usage.

Nanosized Prussian blue and its analogs for bioimaging and cancer theranostics.

Prussian blue (PB) nanoparticles (NPs) and Prussian blue analogs (PBAs) can form metal-organic frameworks through the programmable coordination of ferrous ions with cyanide. PB and PBAs represent a burgeoning class of hybrid functional nano-systems with a wide-ranging application spectrum encompassing biomedicine, cancer diagnosis, and therapy. A comprehensive overview of recent advancements is crucial for gaining insights for future research. In this context, we reviewed the synthesis techniques and surface modification strategies employed to tailor the dimensions, morphology, and attributes of PB NPs. Subsequently, we explored advanced biomedical utilities of PB NPs, encompassing photoacoustic imaging, magnetic resonance imaging, ultrasound (US) imaging, and multimodal imaging. In particular, the application of PB NPs-mediated photothermal therapy, photodynamic therapy, and chemodynamic therapy to cancer treatment was reviewed. Based on the literature, we envision an evolving trajectory wherein the future of Prussian blue-driven biological applications converge into an integrated theranostic platform, seamlessly amalgamating bioimaging and cancer therapy. STATEMENT OF SIGNIFICANCE: Prussian blue, an FDA-approved coordinative pigment with a centuries-long legacy, has paved the way for Prussian blue nanoparticles (PB NPs), renowned for their remarkable biocompatibility and biosafety. These PB NPs have found their niche in biomedicine, playing crucial roles in both diagnostics and therapeutic applications. The comprehensive review goes beyond PB NP-based cancer therapy. Alongside in-depth coverage of PB NP synthesis and surface modifications, the review delves into their cutting-edge applications in the realm of biomedical imaging, encompassing techniques such as photoacoustic imaging, magnetic resonance imaging, ultrasound imaging, and multimodal imaging.