Aug 2026· International Journal of Nanomedicine· Vol 21, pp. 1-24· 0 citations· 179 references
Medicine
TL;DR
This review critically evaluate PNP design strategies, emphasizing stimuli-responsive release mechanisms that enable spatiotemporally controlled drug delivery within the TME, thereby enhancing efficacy and minimizing systemic toxicity.
Abstract
Abstract Malignant tumors remain one of the most serious challenges to global health. Although chemotherapy and targeted therapy are available treatment options, their effectiveness is often limited by the complexity of the tumor microenvironment (TME). In recent years, immunotherapy has demonstrated significant potential in harnessing the immune system to combat cancer. Polymeric nanoparticles (PNPs) have emerged as versatile platforms for cancer immunotherapy, offering favorable biocompatibility, tunable size, and surface functionalization for targeted delivery. In this review, we critically evaluate PNP design strategies, emphasizing stimuli-responsive release mechanisms that enable spatiotemporally controlled drug delivery within the TME, thereby enhancing efficacy and minimizing systemic toxicity. We further highlight PNP-enabled synergistic therapies, including photodynamic, chemodynamic, and sonodynamic therapies, that induce immunogenic cell death (ICD) and potentiate antitumor immunity, as well as PNP-based vaccines (RNA, peptide, and in situ) that activate dendritic cells (DCs) and cytotoxic T lymphocytes (CTLs). Nevertheless, the clinical translation of PNP-based therapies is constrained by multiple factors, including manufacturing scalability, emulsifier-related toxicity, rapid RES clearance, inherent immunogenicity, and the heterogeneity of the TME. By bridging material engineering with immunological barriers and translational challenges, this review provides a critical framework for designing next-generation PNP immunotherapies toward personalized cancer treatment.
This review comprehensively highlights the latest advancements in using nanotechnology to enhance cancer immunotherapy and highlights synergistic effects achieved by combining nanoparticles with other treatments like chemotherapy, radiation, photothermal/photodynamic therapy, and more, which can turn hard-to-treat tumors into susceptible targets.
U. Cho, Jing-Jing Pu, Amit Sharma et al.· Molecular Cancer· 0 citations
Cancer immunotherapy has transformed oncology, however, its clinical efficacy remains limited by immunosuppressive tumor microenvironments (TMEs), poor therapeutic delivery, systematic toxicity, treatment resistance. Chitosan, a biocompatible and biodegradable polysaccharide, has emerged as a versatile biomaterial capable of addressing these challenges through both intrinsics immunomodulatory activity and advanced drug-delivery functions. This review summarizs recent advances in chitosan-based biomaterials for cancer immunotherapy, highlighting their ability to activate innate and adaptive immune responses through pathways involving patterns recognition receptors, cyclic GMP-AMP synthase (cGAS)=simulator of interferon genes (STING) signaling, dendric cells (DCs)macrophages, natural killer (NK) cells and T lymphocytes. The design and application of chitosan-based nanoparticles and hydrogels as platformsfor delivering cytokines, nucleic acids, immune adjuvant, cancer vaccines and immune checkpoint therapeutics are discussed. Particular attention is given to their roles in TME remodeling, sustained local drug release, postsurgical immunotherapy, and combination approaches that integrate chemotherapy, radiotherapy (RT), phototherapy and immunotherapy. Emerging strategies, including stimuli-responsive systems, biomimetic formulations, and multifunctional nanoplatforms are also discussed. Finally, we discuss the current translational current translational challenges and future perspectives, emphasizing the potential of chitosan-based biomaterials to enhance antitumor immunity and improve clinical outcomes in cancer immunotherapy. Chitosan biomaterials enhance antitumor immunity through intrinsic immunomodulatory activity. Chitosan nanoparticles and hydrogels enable efficient delivery of immunotherapeutic agents. Chitosan-based systems remodel the tumor microenvironment and promote immune activation. Combination therapies that integrate chitosan platforms improve therapeutic efficacy and reduce toxicity. Stimuli-responsive and multifunctional chitosan nanoplatforms offer promising strategies for precision cancer immunotherapy.
Yun Wang, Yan Fan, Jing Zhang et al.· Journal of Nanobiotechnology· 1 citation
Chemoimmunotherapy has emerged as a promising strategy for cancer treatment by combining the cytotoxic effects of chemotherapy with the durable immune activation achieved through immunotherapy. However, clinical translation remains limited by poor tumor targeting, systemic toxicity, heterogeneous tumor microenvironments, and inadequate immune activation. Nanocarrier-based delivery systems have recently gained considerable attention because they enable co-delivery of chemotherapeutic and immunotherapeutic agents, controlled drug release, enhanced tumor accumulation, and modulation of the tumor microenvironment. This review summarizes the recent advances in lipid-, polymer-, inorganic-, and biomimetic nanocarriers for synergistic Chemoimmunotherapy. The review also discusses emerging delivery platforms including metal-organic frameworks, extracellular vesicles, stimuli-responsive systems, tumor accumulation mechanisms, current clinical progress, and future translational challenges.
Harshada Salunke, S. Shafi, S. Syed· Health Nanotechnology· 0 citations
The clinical reach of cancer immunotherapy is currently limited by off-target toxicity, physical barriers in solid tumors, and the complex manufacturing of personalized cell therapies. This review presents multi-scale systemic immune programming as a transformative approach, in which lipid nanoparticles (LNPs) function not merely as delivery vehicles but as programmable platforms that direct immune responses across biological scales. At the molecular and cellular levels, LNP design and intracellular delivery regulate mRNA stability, translation, and antigen presentation. At the tissue level, intratumoral mRNA delivery reprograms the tumor microenvironment to overcome stromal barriers and immunosuppression. At the systemic level, LNPs coordinate immune responses, including in vivo CAR-T engineering and vaccine-driven immune memory. At the organismal level, liver-targeted LNPs restore metabolic regulators, reverse cachexia, and improve host resilience. Building on this framework, we propose a dual-track therapeutic paradigm that integrates tumor-directed immune activation with host physiological restoration. Together, this approach positions LNP-based therapies to treat cancer as a systemic immune-metabolic disorder rather than a localized disease.
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
Current evidence supports bacteria as a promising precision modality, particularly for immunologically “cold” or hypoxic tumors; however, major challenges remain in the predictability of intratumoral distribution, host clearance, genetic stability, and long-term safety.
Arman H. Sharifi, Ngoc Hai Trieu Phong, Anjali Marek et al.· Molecular Biomedicine· 0 citations
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