Bridging the Translational Gap in Cancer Nanomedicine: A Systematic Review of Preclinical Benefits and Clinical Challenges

Abstract

Introduction: Despite notable advancements in cancer therapy, conventional treatments continue to face significant limitations, including nonspecific distribution, systemic toxicity, and frequent therapeutic failure due to drug resistance. Nanomedicine has emerged as a promising alternative by enabling targeted delivery of chemotherapeutics through engineered nanoscale carriers that improve drug solubility, stability, and selective accumulation in tumors. Although numerous preclinical studies report enhanced efficacy and reduced toxicity using nanoparticles in animal models, only a small number of these systems have succeeded in clinical translation.

Methods: This systematic review assessed the therapeutic efficacy of nanoparticle-based cancer treatments in animal models and examined the translational challenges preventing their successful implementation in humans. Forty peer-reviewed studies published between 2004 and 2025 were selected from academic databases including PubMed, Scopus, ScienceDirect, Nature, SpringerLink, and Frontiers. Studies were included based on the use of nanoparticles in preclinical cancer models with reported outcomes on efficacy, toxicity, or clinical development status.

Results: Preclinical investigations consistently demonstrated that nanoparticle systems, including liposomes, polymeric carriers, inorganic particles, and stimuli-responsive platforms, improve tumor accumulation, reduce off-target toxicity, and induce stronger therapeutic responses than conventional drugs. Active targeting strategies, such as ligand-mediated or tumor microenvironment-responsive designs, further enhanced selectivity and efficacy. However, less than 1% of the injected nanoparticle dose typically reaches solid tumors in human patients. This stark discrepancy arises from biological and technical barriers, including poor predictive power of animal models, rapid immune clearance, tumor heterogeneity, manufacturing complexities, and regulatory constraints.

Discussion: The findings underscore the limitations of current preclinical tools in forecasting clinical outcomes. While existing platforms show potent antitumor activity in animals, their clinical benefit is limited unless designs account for human-specific pharmacokinetics and immunological responses. Innovations such as humanized models, biomarker-guided patient selection, and artificial intelligence-driven nanoparticle optimization are beginning to address these issues.

Conclusion: To unlock the clinical potential of nanomedicine, future development must integrate advanced preclinical systems, precision targeting, and interdisciplinary collaboration. This review highlights the critical gaps and offers a roadmap toward more effective and translatable nanotherapeutic strategies in cancer care.