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Polyethylene glycol-modified phospholipids (PL-PEG) are widely used to disperse SWCNTs for in vivo applications; however, whether this formulation represents the optimal PEGylation strategy, particularly under repeated administration, remains unclear. Here, we perform a systematic head-to-head comparison between conventional 5 kDa PL-PEG\/SWCNTs and SWCNTs encapsulated within a PEG-based cross-linked polymer network synthesized via CNT micelle polymerization. Quantitative biodistribution analysis using Raman spectroscopy demonstrates that cross-linked PEG\/EAA\/SWCNTs exhibit blood circulation profiles and tumor accumulation comparable to those of PL-PEG\/SWCNTs following initial intravenous injection in mice. Striking differences emerge upon repeated dosing. PL-PEG\/SWCNTs display reduced systemic exposure consistent with accelerated blood clearance (ABC)-like pharmacokinetics, accompanied by a trend of increased hepatic accumulation. In contrast, PEG\/EAA\/SWCNTs maintain largely preserved pharmacokinetic profiles (ABC index \u2248 0.8\u20130.9) and induce significantly lower anti-PEG IgM responses. These results suggest that the observed differences are attributable to differences in PEG molecular weight and\/or PEG presentation architecture. By expanding the design space beyond the widely used PL-PEG standard, this study identifies PEG\/EAA\/SWCNTs as a promising alternative formulation for repeated-dose biomedical applications and highlights the importance of systematically evaluating PEG molecular weight and surface presentation in future studies.<\/jats:p>","DOI":"10.1021\/acsabm.6c00899","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T22:01:35Z","timestamp":1790546495000},"page":"9514-9526","source":"Crossref","is-referenced-by-count":0,"title":["PEG Surface Design Modulates Repeated-Dose Pharmacokinetics of Single-Walled Carbon Nanotubes"],"prefix":"10.1021","volume":"9","author":[{"given":"Ryo","family":"Hamano","sequence":"first","affiliation":[{"name":"Kyushu University , , 744 Motooka , ,","place":["Fukuoka, Japan, 819-0395"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazaya","family":"Najmina","sequence":"additional","affiliation":[{"name":"Kyushu University , , 744 Motooka , ,","place":["Fukuoka, Japan, 819-0395"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Kyushu University , , 744 Motooka , ,","place":["Fukuoka, Japan, 819-0395"]},{"name":"Kyushu University , , 744 Motooka , ,","place":["Fukuoka, Japan, 819-0395"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teruki","family":"Nii","sequence":"additional","affiliation":[{"name":"Kyushu University , , 744 Motooka , ,","place":["Fukuoka, Japan, 819-0395"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Katayama","sequence":"additional","affiliation":[{"name":"Kitakyushu College , , ,","place":["Fukuoka, Japan, 802-0985"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1821-5427","authenticated-orcid":true,"given":"Takeshi","family":"Mori","sequence":"additional","affiliation":[{"name":"Kyushu University , , 744 Motooka , ,","place":["Fukuoka, Japan, 819-0395"]},{"name":"Kyushu University , , 744 Motooka, Nishi-ku , ,","place":["Fukuoka, Japan, 819-0395"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3563-8234","authenticated-orcid":true,"given":"Tsuyohiko","family":"Fujigaya","sequence":"additional","affiliation":[{"name":"Kyushu University , , 744 Motooka , ,","place":["Fukuoka, Japan, 819-0395"]},{"name":"Kyushu University , , 744 Motooka , ,","place":["Fukuoka, Japan, 819-0395"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"2026101904070005000_cit1","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1038\/363603a0","article-title":"Single-shell carbon nanotubes of 1-nm diameter","volume":"363","author":"Iijima","year":"1993","journal-title":"Nature"},{"key":"2026101904070005000_cit2","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1126\/science.1072631","article-title":"Band gap fluorescence from individual single-walled carbon nanotubes","volume":"297","author":"O'Connell","year":"2002","journal-title":"Science"},{"key":"2026101904070005000_cit3","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.physrep.2004.10.006","article-title":"Raman spectroscopy of carbon nanotubes","volume":"409","author":"Dresselhaus","year":"2005","journal-title":"Phys. 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