Advances in carbohydrate polymer-based stimuli-responsive nanocarriers: precision strategies for overcoming multidrug resistance in targeted cancer therapy.

ZIF-8 Nanodrug Delivery Systems: Construction Strategies, Functional Modifications, and Advances in Synergistic Tumor Therapy

Abstract Conventional chemotherapeutic agents are commonly hampered by off-target toxicity and multidrug resistance. Although nanoscale delivery systems can enhance targeting and controlled release, they are frequently constrained by insufficient drug-loading capacity. Zeolitic imidazolate framework-8 (ZIF-8), a metal–organic framework self-assembled from Zn2+ and 2-methylimidazole, features pH-triggered degradability, high drug payload, and favorable biocompatibility. This review systematically evaluates ZIF-8-based cancer therapeutic platforms, comparing synthetic routes (batch preparation versus scalable production), drug-loading strategies (one-pot versus impregnation methods), and functional modification approaches (PEGylation, folic acid conjugation, hyaluronic acid decoration, RGD peptide grafting, and cell-membrane coating) with respect to their efficacy in overcoming current limitations. The core section highlights multimodal combination therapies integrating chemotherapy, photothermal/photodynamic therapy, gene therapy, and immunotherapy. Furthermore, we discuss translational obstacles, including heterogeneous enhanced permeability and retention (EPR) effects, manufacturing reproducibility, and regulatory hurdles, with the goal of comprehensively unleashing the potential of ZIF-8. We conclude that ZIF-8 represents a versatile platform; however, its clinical application necessitates a paradigm shift from empirical design to mechanism-driven engineering, alongside standardized scalable production.

Design of Multi-Stimuli Responsive Nanocarriers for Co-delivery of Phytochemicals and Immune Modulators: A Synergistic Approach to Overcoming Tumor Resistance

Tumor Microenvironment-Responsive Polymeric Nanocarriers for the Treatment of Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous subtype lacking effective targeted therapies. Its tumor microenvironment (TME) exhibits distinct features, including acidity, redox imbalance, elevated reactive oxygen species (ROS), and hypoxia, which provide exploitable triggers for targeted drug delivery. Stimuli-responsive polymeric nanocarriers have emerged as promising platforms that enable spatiotemporally controlled and site-specific therapeutic release in response to these endogenous cues, as well as exogenous stimuli such as temperature and light. These systems improve drug accumulation, penetration, and therapeutic efficacy while reducing systemic toxicity. Unlike previous reviews that broadly discuss nanocarriers in cancer therapy, this review focuses on the structure–function relationships of TME-responsive polymeric systems in TNBC and their translational limitations. We summarize recent advances in pH-, redox-, ROS-, hypoxia-, photo- and temperature-responsive polymers, highlighting their design strategies and therapeutic applications. Key challenges, including stimulus heterogeneity, limited in vivo validation, and clinical translation barriers, are also discussed. This review provides a concise framework for the rational design of programmable, multi-responsive polymeric nanomedicines for TNBC therapy.

Next-generation nanocarriers for synergistic Chemoimmunotherapy: engineering the tumor microenvironment for precision cancer treatment

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.

Cancer Drug Delivery with Nanoparticles and Biomolecules: Stimuli-Responsive, Theranostic, and AI-Guided Approaches

Cancer remains a major global health challenge, and the limitations of conventional therapies, including systemic toxicity, drug resistance, and poor tumor selectivity, continue to drive the development of advanced nanomedicine strategies. In this context, nanocarriers offer promising opportunities to improve pharmacokinetics, enhance tumor accumulation, and enable controlled or stimuli-responsive drug release. Among them, inorganic nanoparticles (NPs) have gained considerable attention because of their structural stability, tunable surface chemistry, and multifunctional capabilities. Their performance depends on a structure–property–function relationship in which composition, morphology, porosity, degradability, and surface characteristics strongly influence interactions at the nano–bio interface. This review examines the main classes of nanoplatforms currently explored for cancer therapy, including inorganic, polymeric, lipid-based, and hybrid organic–inorganic systems. Particular attention is given to the trade-offs that define each platform in terms of loading capacity, biodegradability, multifunctionality, and translational potential. The discussion also highlights the role of predictive biological models, emphasizing that 3D spheroids, organoids, and organ-on-chip systems provide more realistic insights than conventional 2D assays for evaluating tumor penetration and microenvironment-responsive delivery. In addition, the review considers emerging directions in AI-guided nanoparticle engineerization design and natural-compound-based nanomedicines, both of which are expanding the therapeutic landscape. Overall, the field is moving toward more integrated, application-specific, and clinically translatable nanomedicine platforms capable of addressing the complex biological barriers of cancer treatment.

Customized multifunctional nanocarriers for cancer therapy: Integrating targeting, imaging, and combination treatment for diverse patient needs

Multifunctional nanocarriers have emerged as a transformative approach in cancer therapy by overcoming traditional limitations such as systemic toxicity, poor tumor selectivity, and multidrug resistance. This review highlights recent advances in the design and application of customizable nanocarrier systems that integrate targeting, imaging, and combination drug delivery for more personalized and population-specific treatments. We examine major nanocarrier platforms, including lipid-based, polymeric, inorganic, and hybrid systems, with particular emphasis on their tunable physicochemical properties and modular architectures that facilitate adaptation to diverse patient populations, including elderly patients and those with treatment-resistant conditions. Functionalization strategies, such as ligand-mediated targeting and stimuli-responsive release, are discussed in the context of improving site-specific delivery and minimizing off-target effects. The integration of imaging agents enables theranostic functionality for real-time treatment monitoring. We also explore co-delivery systems for synergistic therapies combining chemotherapy, immunomodulation, and phototherapy. Clinical progress, regulatory challenges, and future trends including AI-driven design and bioinspired materials are discussed. This review underscores the pivotal role of multifunctional nanocarriers in advancing precision and inclusive oncology.