Aug 2026· Seminars in Oncology· Vol 53 5, pp.
152537
· 0 citations· 175 references
Medicine
TL;DR
This review elucidates not only the features and components of the TME, but also explains the synthesis and mechanisms of action of AgNPs and puts in context their various applications in nanomedicine and cancer treatment.
Abstract
One of the world's major health challenges is cancer, which arises from sequential genetic and epigenetic alterations leading to tumor development and progression. The tumor microenvironment (TME), which consists of heterogeneous stroma and immune cells, is central to cancer progression, angiogenesis, immune evasion, and metastasis. TME modulation has become a potential strategy for cancer prevention and therapy. Nanoparticles of silver (AgNPs) possess distinct physicochemical characteristics that make them attractive candidates for therapeutic use via their capacity to generate oxidative stress, impair intracellular mechanisms, and impact immune signaling. This review elucidates not only the features and components of the TME, but also explains the synthesis and mechanisms of action of AgNPs, and puts in context their various applications in nanomedicine and cancer treatment. Although AgNPs show promising anticancer activity, toxicity, environmental risk, and clinical translation are still dominant areas for future research.
Advances in nanotechnology have produced a range of strategies for cancer treatment. Among the materials under investigation, Gold Nanoparticles (AuNPs) are attractive candidates for immunotherapy because of their distinctive physicochemical properties and biocompatibility.
This narrative review draws on studies retrieved from PubMed, Scopus, and Web of Science between 2020 and 2025 and describes the mechanisms, therapeutic applications, and clinical development of AuNPs.
AuNPs enhance immune responses by delivering antigens to dendritic cells and T cells and by remodeling the tumor microenvironment. Their photothermal and photodynamic properties damage tumors while activating immunity. Surface modification reduces systemic toxicity, and PEGylation and ligand conjugation improve targeting. Preclinical and early clinical studies indicate that AuNPs can enhance tumor regression and improve treatment response.
AuNPs can serve in drug delivery, immune modulation, and photothermal therapy. Although the results are promising, challenges remain in large-scale synthesis, long-term safety, and regulatory approval. Addressing these factors is essential for successful clinical translation.
Gold nanoparticles represent a promising development in cancer immunotherapy, combining targeted delivery, immune activation, and photothermal effects. Continued optimization and safety evaluation will be essential if AuNPs are to become integral to next-generation personalized cancer treatment. Unlike previous reviews, this work provides a systems-level framework for AuNP-based cancer immunotherapy by integrating mechanistic data, translational bottlenecks, and quantitative comparisons between synthesis methods and nanocarrier systems.
V. R. Jallepalli, Angum M. M. Ibrahim, Anasuya Patil et al.· Current Nanomedicine· 0 citations
Cancer is a group of diseases caused by dysregulation of pathways governing the cell cycle, DNA repair, metabolism, apoptosis, and microRNA expression, among others. It is the second-leading cause of death globally after cardiovascular disease. Early detection and targeted drug delivery with low toxicity towards normal cells are key elements of cancer cell ablation. However, despite tremendous advances in modern cancer therapies, shortcomings such as reduced bioavailability, chronic pain, and adverse health effects impede their efficiency. These challenges have spurred alternative research directions in cancer treatment. Nanotechnology is an emerging field with vast possibilities for biomedical applications. Metal oxide nanoparticles offer enormous potential as agents for diagnosing and treating malignancies. Zn is a ubiquitous trace element that plays a significant role in biological processes. Nanoparticles developed using zinc oxide (ZnO NPs) are biocompatible, biodegradable, and low-toxicity, with promising potential as anticancer agents. Their anticancer potential stems from their ability to trigger ROS production, induce apoptosis, target cancer cells for drug delivery, and prevent cancer recurrence and metastasis. This review explores the dysregulated mechanisms involved in carcinogenesis, the anti-proliferative activity of ZnO NPs, and their proficiency in target drug delivery to tumour cells, using Google Scholar®, SciFinder® and PubMed® as search engines. Additionally, the potential shortcomings and prospects of zinc oxide nanoparticles in cancer treatment strategies are discussed.
Badmus Jelili Abiodun, O. Afolabi· Discover Pharmaceutical Scie...· 0 citations
The clinical benefits of cancer immunotherapy are primarily limited by low response rates and an immunosuppressive tumor microenvironment (TME). Metal elements such as iron, manganese, copper, and zinc, as essential micronutrients for the body, play a key regulatory role in the development and effector functions of immune cells, giving rise to the interdisciplinary field of metalloimmunology. However, the poor tumor-targeting ability of free metal ions, their high systemic toxicity, and rapid in vivo metabolism severely hinder their clinical translation. This review systematically summarizes research progress on metal nanomedicines as smart delivery systems in tumor immunotherapy, outlining design paradigms for nanoplatforms from an engineering perspective, covering microenvironment-responsive release, active targeting strategies, and multifunctional integration concepts. It elucidates the molecular mechanisms by which metal ions regulate antitumor immunity by inducing immunogenic cell death (ICD), activating the stimulator of interferon genes (STING) signaling pathway, and reshaping the metabolic microenvironment, and explores synergistic strategies combining metal nanomedicines with immune checkpoint blockade (ICB), photothermal therapy (PTT), or photodynamic therapy (PDT). Unlike previous reviews that often focus on either the immunological functions of metal ions or the engineering of nanocarriers in isolation, this review provides an integrated framework that explicitly links metal ion identity, immune pathway engagement, nanoplatform design parameters, and translational barriers. Central to this framework is a mechanism-design matching principle that connects the specific temporal and intensity requirements of each immune activation pathway with tailored material selection and release kinetics. These immune effects are context-dependent and may vary in selected preclinical models. This paper integrates metallobiology, nanomedicine, and tumor immunology to provide a theoretical framework for the precise design of smart metal immunotherapeutics, while identifying key challenges for clinical translation, such as the therapeutic safety window and metal homeostasis compensation mechanisms.
Shuyong Yan, Fei Zhou· Frontiers in Chemistry· 0 citations
Breast cancer is also one of the most common causes of cancerrelated
deaths in the world, and this is mainly because of the therapeutic resistance and
immune evasion mechanisms in the tumor microenvironment. An immunosuppressive
tumor microenvironment, characterized by dysfunctional immune cells and stromal impediments,
limits the efficacy of traditional treatments. The strategies of modulating the
tumor immune microenvironment using nanoparticles have become promising in improving
the outcome of immunotherapies.
A structured narrative review was conducted to evaluate the current
evidence on nanoparticle-mediated immune modulation in breast cancer. A comprehensive
literature search was performed in the PubMed, Scopus, and Web of Science databases
to identify relevant studies published between 2015 and 2025. Eligible studies included
mechanistic, preclinical (in vitro and in vivo), and clinical investigations examining
nanoparticle-based immunotherapeutic approaches and their effects on the breast cancer
tumor immune microenvironment.
Nanoparticle-based systems, such as lipid-, polymeric-, inorganic-, and biomimetic
systems, can be used to deliver therapeutic agents that target key immune components,
including tumor-associated macrophages, regulatory T cells, and Cytotoxic T
Lymphocytes (CTLs)s. These systems increase antigen presentation and (ICD), which can
be used to boost anti-tumor immune responses. Nonetheless, clinical translation remains
inadequate due to tumor heterogeneity, transport barriers mediated by the extracellular
matrix (ECM), variable delivery efficiency, and safety concerns.
Immunomodulatory strategies using nanoparticles enable immune reprogramming
and enhance therapeutic targeting in the tumor microenvironment. Although
promising preclinical results have been obtained, clinical use is limited due to variable
intratumoral distribution, non-uniform immune interactions, and the lack of standardized
assessment systems. These issues need to be addressed to enhance translational success.
Nanoparticle-mediated immune modulation is a prospective approach to
overcome immunosuppression in breast cancer. Future studies must aim to design nanoparticles
that maximize tumor uptake, incorporate predictive biomarkers, and optimize
clinical utility and therapeutic efficacy.
A. Singh, Shatrudhan Prajapati, Shikha Yadav et al.· Current Pharmacogenomics and...· 0 citations
A translational framework for overcoming key barriers in pharmaceutical intervention design for oncology applications is outlined, integrating drug delivery engineering, molecular biopharmaceutics, and computational optimization.
Manoj Dalabehera, Shubham K. Chaudhari, Jatin Kumar et al.· Journal of Pharmacy and Scie...· 0 citations
Breast cancer treatment remains limited by drug resistance, toxicity, and inadequate selectivity in aggressive subtypes, prompting continued interest in selenium-based agents whose anticancer activity depends strongly on chemical form, redox behavior, and metabolic fate. This review critically compares inorganic, organic, and nanoscale selenium, with particular emphasis on selenium nanoparticles (SeNPs) as engineerable platforms for breast cancer therapy. Current evidence indicates that selenium-based agents primarily exert antitumor effects through disruption of redox homeostasis, induction of apoptosis, and modulation of survival signaling pathways such as PI3K/AKT/mTOR, while additional effects on autophagy, metastasis, angiogenesis, and treatment resistance appear to be more context-dependent. Compared with conventional selenium compounds, SeNPs offer greater formulation flexibility through surface modification, cargo loading, and stimulus-responsive design, and have shown promising activity especially in triple-negative and HER2-positive breast cancer models. However, clinical translation is restricted by the lack of breast cancer-specific early-phase therapeutic studies and by persistent uncertainties regarding the therapeutic window, pharmacokinetics, long-term safety, manufacturing reproducibility, and patient selection. By integrating selenium speciation, SeNP preparation strategies, subtype-oriented applications, and translational barriers, this review highlights that future progress will depend on standardized formulations, rigorous in vivo validation, and biomarker-informed clinical development rather than unselected selenium use.
Hui-Jia Ni, Xu Fu, Xiaoyu Chen et al.· Frontiers in Oncology· 0 citations
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