{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:04:51Z","timestamp":1787321091812,"version":"build-2736575974"},"reference-count":63,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"848","funder":[{"DOI":"10.13039\/501100003038","name":"Elektrobit","doi-asserted-by":"publisher","award":["NIH R35 GM131728"],"award-info":[{"award-number":["NIH R35 GM131728"]}],"id":[{"id":"10.13039\/501100003038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003038","name":"Elektrobit","doi-asserted-by":"publisher","award":["NIH K08 HL153782"],"award-info":[{"award-number":["NIH K08 HL153782"]}],"id":[{"id":"10.13039\/501100003038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003038","name":"Elektrobit","doi-asserted-by":"publisher","award":["NIH R01 HL117952"],"award-info":[{"award-number":["NIH R01 HL117952"]}],"id":[{"id":"10.13039\/501100003038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003038","name":"Elektrobit","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003038","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Stuart and Jane Weitzman Family Vascular Anomalies Fund"},{"name":"MCC Ignite"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,5,6]]},"abstract":"<jats:p>\n                    Venous malformations (VMs) are caused by activation of the phosphoinositide 3-kinase (PI3K)\/protein kinase B (AKT)\/mechanistic target of rapamycin (mTOR) and Abelson murine leukemia viral oncogene homolog 1 (c-ABL) pathways. Daily oral administration of rapamycin (RAPA), an mTOR pathway inhibitor, has limited effectiveness in promoting lesion regression in patients with\n                    <jats:italic toggle=\"yes\">TEK<\/jats:italic>\n                    receptor tyrosine kinase (TIE2)\u2013mutated VMs. This may be due to poor bioavailability, frequent dosing requirements, and off-target effects that make maintaining adherence difficult. Recent preclinical studies have shown that combination treatment with RAPA and a c-ABL inhibitor [ponatinib (PON)] resulted in regression of VMs in a murine model; however, daily oral dosing was required. Here, we describe the formulation of polymeric RAPA, which acts as both a polymeric drug and a drug delivery carrier. The polymer was synthesized by polymerization of methacryloylated RAPA and terminated with polyethylene glycol (PEG-pRAPA). PEG-pRAPA self-assembled to form 30-nanometer nanoparticles (PEG-pRAPA NPs) and enabled the encapsulation of PON (PEG-pRAPA@PON NPs). PEG-pRAPA@PON NPs provided sustained release of both PON and PEG-pRAPA in vitro, reducing AKT phosphorylation comparably to free RAPA and PON. In a murine model of VMs, a single intravenous dose of PEG-pRAPA@PON NPs caused 70% VM regression over 20 days and a 6.3-fold reduction in CD31-positive (human-derived) blood vessels. There was no evidence of systemic toxicity or organ dysfunction after treatment. These findings demonstrated that PEG-pRAPA is an effective polymeric drug and drug delivery platform and support the hypothesis that nanoparticle-based pharmacotherapy can be an effective treatment strategy for VMs.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.aeb7597","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T17:59:53Z","timestamp":1778090393000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Polymeric rapamycin nanoparticles encapsulating ponatinib cause regression of venous malformations in mice"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7113-9366","authenticated-orcid":true,"given":"Weimin","family":"Tang","sequence":"first","affiliation":[{"name":"Laboratory for Biomaterials and Drug Delivery, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Department of Medicine Critical Care, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5905-3114","authenticated-orcid":true,"given":"Ysabel","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory for Biomaterials and Drug Delivery, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Department of Medicine Critical Care, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6996-0419","authenticated-orcid":true,"given":"Elisa","family":"Boscolo","sequence":"additional","affiliation":[{"name":"Division of Experimental Hematology and Cancer Biology, Cincinnati Children\u2019s Hospital, University of Cincinnati, Cincinnati, OH 45229, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5369-5932","authenticated-orcid":true,"given":"Daniel S.","family":"Kohane","sequence":"additional","affiliation":[{"name":"Laboratory for Biomaterials and Drug Delivery, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Department of Anesthesiology, Critical Care, and Pain Management, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9803-656X","authenticated-orcid":true,"given":"Kathleen","family":"Cullion","sequence":"additional","affiliation":[{"name":"Laboratory for Biomaterials and Drug Delivery, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Department of Medicine Critical Care, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, 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