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The standard chemotherapy remains the conventional \u201c7+3\u201d regimens, while the suboptimal pharmacokinetics and significant systemic toxicity in AML present ongoing challenges to long-term disease control. Nano-drug delivery systems (NDDSs) have emerged as a promising strategy to overcome these barriers by enabling enhanced drug stability, targeted delivery, and specific distribution. Although several NDDS-based therapies have been approved by FDA, the clinical translation of nanomedicine in AML remains limited. This is largely due to the unique pathophysiology of AML, which lacks the vascular structures found in solid tumors, resulting in a limited and atypical enhanced permeability and retention (EPR) effect. Active targeting strategies, including antibody, aptamer, and peptide-based ligand modifications, offer a compelling approach to improve cellular specificity and therapeutic efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this review, we provide a comprehensive overview of NDDSs engineered for AML, focusing on recent advances in active targeting approaches, their mechanistic advantages, and translational challenges.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Current active-targeting NDDSs in AML generally follow two major directions. One direction focuses on surface receptors that are aberrantly overexpressed on AML cells, thereby improving payload specificity. The other direction focuses on bone marrow (BM)-targeted nanocarriers that utilize cell homing mechanisms and disease-associated markers of the BM microenvironment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>NDDSs designed for different targets, carrier materials, and release mechanisms have demonstrated improved pharmacodynamic effects, but they remain at the preclinical stage. Based on a summary of the current challenges facing NDDSs, this review further discusses key directions for next-generation system design, such as the development of personalized carriers, reduction of off-target effects, and more effective delivery to leukemia stem cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-026-07792-0","type":"journal-article","created":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T10:54:14Z","timestamp":1770461654000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Overcoming therapeutic challenges in acute myeloid leukemia: active targeting strategies by nano-drug delivery systems"],"prefix":"10.1186","volume":"24","author":[{"given":"Yuqian","family":"Tang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wu","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxia","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2437-9348","authenticated-orcid":false,"given":"Yuping","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,7]]},"reference":[{"issue":"12","key":"7792_CR1","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1182\/blood.2022016867","volume":"140","author":"H D\u00f6hner","year":"2022","unstructured":"D\u00f6hner H, Wei AH, Appelbaum FR, Craddock C, DiNardo CD, Dombret H, et al. 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