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.
Abstract
Cancer immunotherapy has substantially advanced cancer treatment, achieving durable responses in select malignancies. However, its widespread application is limited by significant challenges: low efficacy in many solid tumors, severe side effects, and immune evasion facilitated by the tumor microenvironment (TME). Nanotechnology offers a promising approach to address these obstacles. By employing nanoparticles (NPs), we can precisely deliver therapeutics to tumor sites, ensure controlled release to minimize side effects, and amplify the immune response, thereby substantially boosting the effectiveness of immunotherapy. This review comprehensively highlights the latest advancements in using nanotechnology to enhance cancer immunotherapy. This paper details various applications of nanotech in this field. It discusses smart nanoparticles that respond to TME signals to release drugs (e.g., checkpoint inhibitors) directly at the tumor, reducing systemic side effects and activating T-cells. We also explore how nanovaccines, which co-deliver tumor markers and immune boosters, can induce antigen-specific immune responses. Furthermore, mRNA-loaded nanoparticles can directly modify CAR T-cells inside the body, simplifying treatment and increasing efficacy. Strategies like using PLGA NPs to deliver immune enhancers such as IL-2 are also presented, which activate immune cells while minimizing systemic issues. The review also explains how nanoparticles can re-engineer the immunosuppressive TME to create an environment more conducive to immune action. We also emphasize that nanotechnology-enhanced adoptive therapies, particularly cytokine-induced killer (CIK) cell immunotherapy, hold great potential to improve tumor targeting, treatment persistence durability, and overall anticancer efficacy. Collectively, we highlight 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. The integration of nanotechnology and immunotherapy holds the potential to meaningfully advance future cancer therapy.
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.
Dong-Qi Li, Jia Hu, Ying-Shu Cui et al.· International Journal of Nan...· 0 citations
This review article focuses on CAR-T cell bioengineering, antitumor mechanism of action, challenges and limitations, as well as the latest innovative nanotechnological solutions for complementing CAR-T cell immunotherapy.
Alaa Ibrahim, Maha Nasr· Biochimica et biophysica act...· 0 citations
Cancer immunotherapy has reshaped cancer treatment by enabling the immune system to recognize and eliminate tumor cells. Nevertheless, its clinical translation remains limited by suboptimal response rates, poor penetration into deep tumor tissues, and insufficient therapeutic efficacy. Cancer immunotherapy alone is often inadequate as a sole treatment modality. Nanomedicine-based therapeutic strategies, including photothermal therapy, photodynamic therapy, sonodynamic therapy, nanozyme-based therapy, and cancer vaccines, have achieved considerable recognition for cancer treatment. Upon integration with cancer immunotherapy or regulated cell death pathways, these nanomedicine-based therapeutic strategies can modulate the tumor microenvironment, enhance anticancer immune response, and overcome immunotherapy resistance. This article summarizes recent advances in nanomedicine-based therapeutic strategies, the role of cancer immunotherapy, and regulated cell death pathways. We outline the strengths and limitations of these therapeutic strategies. We also discuss how combination therapeutic strategies achieve synergistic effects, future challenges, and perspectives in developing next-generation nanomedicine platforms for cancer immunotherapy.
Brynne Shu Ni Tan, Yanli Zhao· ACS Applied Materials and In...· 0 citations
Next-generation personalized cancer vaccines are advancing the transition from reactive treatment to proactive, precision-controlled cancer immunotherapy, and when integrated with artificial intelligence for antigen selection and multiomics for patient stratification, these platforms accelerate vaccine design and improve precision.
L. Ye, GuoWei Zhao, Jiaxiu Ma et al.· Signal Transduction and Targ...· 1 citation
Purpose: Cancer immunotherapy works by targeting immune and cancer cell checkpoints to induce long-term anti-tumor responses, showing effectiveness in inhibiting tumor growth and preventing recurrence. However, clinical trials have also reported side effects, as well as resistance in some patients with melanoma, prompting the integration of nanotechnology with immunotherapy to improve outcomes. RNA nanotechnology has emerged as a transformative approach in cancer immunotherapy, particularly in the context of treating melanoma. The review also highlights the challenges and future directions of RNA nanotechnology-mediated cancer immunotherapy in melanoma, underscoring its potential to transform treatment strategies. Methods: A narrative review of the recent literature was conducted, focusing on RNA nanotechnology applications in melanoma immunotherapy. Studies investigating RNA-based nanoparticles, RNA delivery systems, immune checkpoint modulation, cytokine regulation, tumor antigen vaccines, and immune-cell-targeted therapeutic strategies were evaluated and summerized. Results: RNA nanotherapeutics have demonstrated the ability to modulate immune checkpoints, reprogram tumor-associated macrophages, enhance antigen presentation, and restore T-cell activity in melanoma models. Lipid nanoparticles, polymeric nanocarriers, and bio-inspired delivery systems have shown improved RNA stability, tumor targeting, and endosomal escape. Emerging clinical evidence from RNA vaccines indicates encouraging immunogenicity and therapeutic potential in advanced melanoma. However, several barriers remain, including tumor heterogeneity, limited penetration into immune-desert metastases, nanoparticle-associated toxicity, manufacturing complexity, and variability of the enhanced permeability and retention effect in human tumors. Conclusion: RNA nanotechnology represents a promising and rapidly evolving platform for melanoma immunotherapy. By enabling precise modulation of immune responses and improving targeted therapeutic delivery, RNA-based nanostructures may overcome several limitations of current immunotherapeutic approaches. Further preclinical and clinical investigations are required to optimize safety, delivery systems, and therapeutic efficacy before widespread clinical implementation can be achieved.
Immunotherapy has rapidly emerged as the new pillar of cancer treatment alongside surgery, radiotherapy and chemotherapy. However, existing immunotherapeutic approaches face significant limitations such as inefficient tumor-targeted drug delivery, poor cellular internalization and off-target effects, all of which lead to suboptimal therapeutic outcomes. Recent advances in nanotechnology have introduced nanomedicines as a promising solution to these challenges, which can precisely deliver immunomodulators, enhance antigen presentation, and increase T-cell infiltration as well as improve their targeting and safety, and thus powerfully enhance the therapeutic effect of tumor immunotherapy. Among numerous types of nanomedicines, biodegradable nanomaterials have recently received extensive attention for tumor immunotherapy due to their unique advantages including biodegradability, simple and cost-effective synthesis, and use of renewable resources, aligning with environmental and sustainable development goals. More importantly, many biodegradable nanomedicine platforms, such as liposomes, polymeric micelles and polymeric nanoparticles, have already entered clinical trials or received approval. Thus, the biodegradable nanomaterials exhibit promising potential for tumor immunotherapy. However, comprehensive reviews systematically summarizing the application of biodegradable nanomaterials for tumor immunotherapy are still rare. Herein, this review provides a detailed introduction to this field. Firstly, the general types of biodegradable nanomaterials for tumor immunotherapy are introduced. Secondly, the common mechanisms of tumor immunotherapy are elucidated. Thirdly, the basic research applications of biodegradable nanomedicine-mediated tumor immunotherapy are emphasized. Next, the clinical transformation prospects of biodegradable nanomaterials for tumor immunotherapy are highlighted. Furthermore, the potential impacts of degradation behaviors on the immune microenvironment are pointed out. Finally, the challenges and future outlooks are discussed.
Ru-Tuan Dong, Shuai-Shuai Ding, Bo-Kai Song et al.· Journal of materials chemist...· 0 citations
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