Tumor Nanomedicine Research Articles

Apoptosis‐Sensitizing Tumor Nanomedicine by Regulating Pyroptosis‐Associated Inflammatory Cell Death

AbstractThe vigorous development of cancer nanomedicine has revolutionized traditional oncology medicine, but it is also limited by the continuous mutation of cunning cancer cells, leading to apoptosis insensitivity and therapeutic disappointment. Inflammatory‐regulated cell death (RCD), especially pyroptosis‐related cell death, demonstrates huge potential for apoptosis sensitization due to its unique biochemical characteristics. The aim of this research is to present a thorough synopsis of the current knowledge on pyroptosis‐associated inflammatory cell death, including pyroptosis, cuproptosis, and PANoptosis, and the synergistic function in cancer nano therapy. Paradigm studies of pyroptosis‐related cell death‐mediated apoptosis‐sensitizing tumor nanotherapeutics are introduced in detail, and the coordination mechanisms based on nanomaterials are also discussed. In addition, multi‐angle analysis of the future prospects of pyroptosis‐sensitized tumor nanomedicine based on various nanomaterials is also emphasized to further expand the application scope of inflammatory RCD. It is believed that emerging auxiliary apoptosis‐sensitizing treatments based on inflammatory RCD will greatly promote the progress of cancer nanomedicine.

Ultrasmall AuCe nanozyme adjuvant boosted ROS for three-pronged tumor immunotherapy

Catalytic tumor immunotherapy presents a new combination of nanozymes and immunotherapy agents, but the final therapeutic outcomes are usually diminished by insufficient nanozyme activity, immunosuppressive tumor microenvironment (TME), and poor antigen delivery efficiency. Herein, a bimetallic nanozyme-based tumor immunotherapy nanovaccine is first proposed to address these limitations by attenuating the immunosuppression of TME and effectively delivering tumor-specific antigens and catalytic tumor nanomedicine. The tumor-specific antigen OVA-templated bimetallic AuCe nanozyme (denoted as ACO) is a nanodot composed of Au cluster and CeOx. The high Ce3+/Ce4+ ratio and charge transfer from Au to Ce synergistically enhance the peroxidase-like activity of ACO. The boosted reactive oxygen species level inhibits the proliferation of B16-OVA cells and simultaneously promotes the maturation of dendritic cells. The functionalization of PD-L1 inhibitory D-peptide on ACO (named ACOD) increases tumor targeting specificity and prolongs tumor site retention, facilitating apoptosis of primary and distant tumor cells and conquering immune evasion. Moreover, ACOD catalytic nanovaccine induces long-term immune memory against tumor recurrence and lung metastasis. Therefore, the bimetallic catalytic nanovaccine is a promising nanoformulation to eradicate cancer and safeguard against tumor relapse.

Application of artificial intelligence in cancer diagnosis and tumor nanomedicine.

Cancer is a major health concern due to its high incidence and mortality rates. Advances in cancer research, particularly in artificial intelligence (AI) and deep learning, have shown significant progress. The swift evolution of AI in healthcare, especially in tools like computer-aided diagnosis, has the potential to revolutionize early cancer detection. This technology offers improved speed, accuracy, and sensitivity, bringing a transformative impact on cancer diagnosis, treatment, and management. This paper provides a concise overview of the application of artificial intelligence in the realms of medicine and nanomedicine, with a specific emphasis on the significance and challenges associated with cancer diagnosis. It explores the pivotal role of AI in cancer diagnosis, leveraging structured, unstructured, and multimodal fusion data. Additionally, the article delves into the applications of AI in nanomedicine sensors and nano-oncology drugs. The fundamentals of deep learning and convolutional neural networks are clarified, underscoring their relevance to AI-driven cancer diagnosis. A comparative analysis is presented, highlighting the accuracy and efficiency of traditional methods juxtaposed with AI-based approaches. The discussion not only assesses the current state of AI in cancer diagnosis but also delves into the challenges faced by AI in this context. Furthermore, the article envisions the future development direction and potential application of artificial intelligence in cancer diagnosis, offering a hopeful prospect for enhanced cancer detection and improved patient prognosis.

Living Cell‐Derived Intelligent Nanobots for Precision Oncotherapy

AbstractThe progress of precision oncology medicine is always limited by the tumor off‐targeting, the drug side effects, and the treatment inefficiency due to the complex and ever‐changing tumor microenvironment. Living cells, such as blood cells and immune cells, exhibit natural tumor tropism, controllable physicochemical modification, and excellent biocompatibility, which provide an advantageous pathway for innovative and efficient tumor suppression. Armed with nanoengineering techniques, artificial living cells harness their inherent biological properties to precisely identify and eradicate tumors, demonstrating broad biological application prospects and great transformational potential in personalized cancer therapy. Here, the recent advances of living cell‐based bionanobots including platelets, red blood cells, neutrophil, macrophage, and CAR‐T cells for cancer precision therapy and immune regulation are summarized, and the efficient anti‐tumor strategies for engineering living cell nanorobots to overcome complex biological barriers and immune suppression are also outlined (e.g., immunotherapy, sonodynamic therapy, chemo/radiotherapy, and phototherapy). In addition, the study discusses the advantages, limitations, and current challenges of artificial living cell‐based drug delivery systems, and provide perspectives on the future development of living cell‐mediated precision tumor nanomedicine.

Exosomes and biomimetic nanovesicles-mediated anti-glioblastoma therapy: A head-to-head comparison

Exosomes (Exos) are promising vehicles for brain drug delivery due to nanosize and the ability to breach the blood–brain barrier (BBB). But the low yield of natural exosomes limits its application for nanomedicine. The generation of bioinspired nanovesicles (BNVs) that mimicking Exos is attractive, but there is a lack of comparative evaluation of Exos and BNVs. Here, we perform the first head-to-head comparison study of Exos and BNVs for brain tumor drug delivery. We show that BNVs derived from brain-derived endothelial cells are competent alternative nanocarrier to natural exosomes. The drug-loading capacity of Exos and BNVs are similar, but the yield of BNVs is substantially higher (500-fold) than Exos. Doxorubicin (DOX)-loaded BNVs (BNV/DOX) and DOX-loaded Exos (Exo/DOX) showed similar pharmacokinetic profiles and prolonged circulation od DOX. Despite inconsistent mechanisms, BNV/DOX can across the BBB, and exhibit suppression effects similar to Exo/DOX on the progress of glioblastoma (GBM) in zebrafish and in vivo subcutaneous and orthotopic xenografts mice models, with minimal systemic toxicity. Findings from this head-to-head comparison study indicate that autologous BNVs is a effective alternative of Exos for brain tumor nanomedicine.

Study on the Effect and Mechanism of Paclitaxel-Succini Acid Drug-Loaded Nanofibers in Treating Lung Cancer.

In recent years, nanotechnology has made great progress in the development and application of tumor detection, diagnosis, and treatment, and eventually formed a "tumor nanomedicine." The emerging field of "materials." Nanoparticles have attracted much attention because they can overcome physiological barriers, effectively deliver hydrophobic drugs, and specifically target tumor tissues. At present, nanomedicines mainly include lipid nanoparticles, polymer nanoparticles granules, gold nanoparticles, magnetic nanoparticles, mesoporous silica, and other dosage forms. The use of nanomaterials as carriers in the treatment of lung cancer has unique advantages in achieving targeted drug delivery, slow-release drugs, and improvement of poorly soluble drugs and peptide drugs show obvious advantages in terms of bioavailability and reduction of adverse reactions, and have broad research and development prospects. This paper reports a new type of self-assembled Ptx-SA drug-loaded nanometers based on the carrier-free concept fiber, and it was found that the drug-loaded fiber has better cellophilicity, anti-tumor effect in vitro and in vivo than naked drug, and may be mediated by regulating the expression of related proteins. Therefore, the paclitaxel-loaded nano drug delivery system serves as a new type of nano preparation for treating lung cancer is worth further research.

Subtherapeutic Photodynamic Treatment Facilitates Tumor Nanomedicine Delivery and Overcomes Desmoplasia.

Limited tumor nanoparticle accumulation remains one of the main challenges in cancer nanomedicine. Here, we demonstrate that subtherapeutic photodynamic priming (PDP) enhances the accumulation of nanoparticles in subcutaneous murine prostate tumors ∼3-5-times without inducing cell death, vascular destruction, or tumor growth delay. We also found that PDP resulted in an ∼2-times decrease in tumor collagen content as well as a significant reduction of extracellular matrix density in the subendothelial zone. Enhanced nanoparticle accumulation combined with the reduced extravascular barriers improved therapeutic efficacy in the absence of off-target toxicity, wherein 5 mg/kg of Doxil with PDP was equally effective in delaying tumor growth as 15 mg/kg of Doxil. Overall, this study demonstrates the potential of PDP to enhance tumor nanomedicine accumulation and alleviate tumor desmoplasia without causing cell death or vascular destruction, highlighting the utility of PDP as a minimally invasive priming strategy that can improve therapeutic outcomes in desmoplastic tumors.

Potentiated cytosolic drug delivery and photonic hyperthermia by 2D free-standing silicene nanosheets for tumor nanomedicine.

Silicene, as an emerging two-dimensional (2D) silicon allotrope, mainly serves in the field of electronics and energy devices but multidisciplinary studies on 2D silicene have been rarely carried out, especially the potential translational biomedical practice. In this study, we explore a high-performance photonic drug-delivery nanoplatform based on 2D ultrathin silicene nanosheets (DOX@silicene-BSA NSs) regarding effective chemotherapeutic drug loading (capacity amount of w/w%: 137.0%) while highlighting the potentiated cytosolic drug-delivery efficiency (spatiotemporally pH-/NIR-triggered drug-release) and NIR-II-activated photonic hyperthermia (η = 19.7%) performance, thus, enabling the potential synergistic chemotherapeutic and phototherapeutic outcomes. The cellular endocytotic mechanism of these nanosheets in cancer cells has been comprehensively studied and provides an essential understanding of the nano-bio interactions of silicene-based nanosheets or other emerging 2D nanostructures. Prominent suppression of tumor growth was achieved by synergistic chemotherapy and photonic hyperthermia with negligible adverse effects and expected degradability, thus addressing the several fundamental barriers of oncology-related nanotherapies. This work highlights silicene, which integrates the merits of high specific surface area endowed with 2D topology, intrinsic responsiveness toward physical/chemical stimuli, and biomedical necessity of biodegradation and biosafety, as a promising next-generation omnipotent alternative to subrogate traditional silicon-based biomaterials and non-biocompatible nanoagents in clinical translation nanomedicine.

Captopril improves tumor nanomedicine delivery by increasing tumor blood perfusion and enlarging endothelial gaps in tumor blood vessels

Poor tumor perfusion and unfavorable vessel permeability compromise nanomedicine drug delivery to tumors. Captopril dilates blood vessels, reducing blood pressure clinically and bradykinin, as the downstream signaling moiety of captopril, is capable of dilating blood vessels and effectively increasing vessel permeability. The hypothesis behind this study was that captopril can dilate tumor blood vessels, improving tumor perfusion and simultaneously enlarge the endothelial gaps of tumor vessels, therefore enhancing nanomedicine drug delivery for tumor therapy. Using the U87 tumor xenograft with abundant blood vessels as the tumor model, tumor perfusion experiments were carried out using laser Doppler imaging and lectin-labeling experiments. A single treatment of captopril at a dose of 100 mg/kg significantly increased the percentage of functional vessels in tumor tissues and improved tumor blood perfusion. Scanning electron microscopy of tumor vessels also indicated that the endothelial gaps of tumor vessels were enlarged after captopril treatment. Immunofluorescence-staining of tumor slices demonstrated that captopril significantly increased bradykinin expression, possibly explaining tumor perfusion improvements and endothelial gap enlargement. Additionally, imaging in vivo, imaging ex vivo and nanoparticle distribution in tumor slices indicated that after a single treatment with captopril, the accumulation of 115-nm nanoparticles in tumors had increased 2.81-fold with a more homogeneous distribution pattern in comparison to non-captopril treated controls. Finally, pharmacodynamics experiments demonstrated that captopril combined with paclitaxel-loaded nanoparticles resulted in the greatest tumor shrinkage and the most extensive necrosis in tumor tissues among all treatment groups. Taken together, the data from the present study suggest a novel strategy for improving tumor perfusion and enlarging blood vessel permeability simultaneously in order to improve nanomedicine delivery for tumor therapy. As captopril has already been extensively used clinically, such a strategy has great therapeutic potential.