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Passive approaches based on the EPR effect enable tumor accumulation but remain limited by tumor heterogeneity, poor penetration, and off-target toxicity. New designs combine active targeting, stimuli-responsive elements, and biomimetic strategies to control spatiotemporal drug release. These nanocarriers recognize molecular signatures, respond to tumor microenvironment cues (pH, redox, hypoxia, enzymatic activity), and can provide feedback via imaging or biosensing modules. 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Next-generation nanocarriers for precision antitumor therapy: from passive targeting to intelligent response. Explor Target Antitumor Ther. 2025;6:1002355. [https://doi.org/10.37349/etat.2025.1002355](https://doi.org/10.37349/etat.2025.1002355)  \nAbstract  \nThe evolution of nanocarrier-based drug delivery systems has transformed the paradigm of cancer therapeutics, advancing from conventional cytotoxic formulations to intelligent, adaptive nanosystems capable of precision targeting. Early-generation nanocarriers exploited the enhanced permeability and retention (EPR) effect for passive tumor accumulation, yet their therapeutic efficiency remained constrained by tumor heterogeneity, limited penetration, and off-target toxicity. Emerging nanotechnologies now integrate active targeting, stimuli-responsive components, and biomimetic strategies to achieve spatiotemporal control over drug release and tumor-selective action. These“intelligent” nanocarriers are designed to recognize molecular signatures, respond dynamically to tumor microenvironmental cues such as pH, redox gradients, hypoxia, and enzymatic activity, and even engage in real-time feedback through imaging or biosensing modules. In addition, hybrid and multifunctional platforms—combining liposomes, micelles, dendrimers, polymeric nanoparticles, and inorganic systems—offer programmable functionality and synergistic delivery of chemotherapeutic, gene-editing, and immunomodulatory agents. This review delineates the mechanistic basis of passive and active targeting, highlights recent innovations in stimuli-responsive and biomimetic nanocarriers, and explores translational and regulatory perspectives shaping their clinical journey. By integrating nanotechnology with systems biology and artificial intelligence, next-generation nanocarriers promise to redefine the landscape of precision antitumor therapy.  \nKeywords  \nnanocarriers, antitumor therapy, EPR effect, active targeting, stimuli-responsive systems, biomimetic nanoparticles, tumor microenvironment, precision medicine  \nIntroduction  \nThe advent of next-generation nanocarriers represents a pivotal advancement in precision antitumor therapy, transitioning from rudimentary passive targeting mechanisms reliant on the enhanced  \n© The Author(s) 2025. This is an Open Access article licensed under a Creative Commons Attribution 4.0 International License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.  \nExplor Target Antitumor Ther. 2025;6:1002355 | [https://doi.org/10.37349/etat.2025.1002355](https://doi.org/10.37349/etat.2025.1002355) Page 1  \npermeability and retention (EPR) effect to sophisticated intelligent systems that respond dynamically to tumor-specific stimuli, thereby optimizing drug delivery, minimizing systemic toxicity, and enhancing therapeutic efficacy [1]. Tradit","cbCais88PV2NBqps","https://ap.wps.com/l/cbCais88PV2NBqps","pdf",3663266,"English","# Exploration of Targeted Anti-tumor Therapy\n## Open Access Review\n## Next-generation nanocarriers for precision antitumor therapy: from passive targeting to intelligent response\n## Abstract\n## Keywords\n## Introduction","[{\"question\":\"What problem limits early nanocarriers that rely on the EPR effect?\",\"answer\":\"Their therapeutic efficiency is constrained by tumor heterogeneity, limited penetration, and off-target toxicity, even though they promote passive tumor accumulation.\"},{\"question\":\"How do next-generation “intelligent” nanocarriers improve precision antitumor therapy?\",\"answer\":\"They integrate active targeting and stimuli-responsive components that recognize molecular signatures and react dynamically to cues in the tumor microenvironment such as pH, redox gradients, hypoxia, and enzymatic activity.\"},{\"question\":\"Which nanocarrier types and payload strategies are highlighted?\",\"answer\":\"The review covers hybrid multifunctional platforms including liposomes, micelles, dendrimers, polymeric nanoparticles, and inorganic systems, enabling delivery of chemotherapeutic drugs, gene-editing agents, and immunomodulatory therapies.\"}]","Next-generation nanocarriers for precision antitumor therapy - from passive targeting to intelligent response | PDF",1790574359,48]