PMID- 38222561 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240116 IS - 2470-1343 (Electronic) IS - 2470-1343 (Linking) VI - 9 IP - 1 DP - 2024 Jan 9 TI - Engineering Temperature-Responsive Polymer Nanoparticles that Load and Release Paclitaxel, a Low-Molecular-Weight Anticancer Drug. PG - 1011-1019 LID - 10.1021/acsomega.3c07226 [doi] AB - Poly(N-isopropylacrylamide) (pNIPAm) undergoes a hydrophilicity/hydrophobicity change around its lower critical solution temperature (LCST). Therefore, pNIPAm-based polymer nanoparticles (NPs) shrink above their LCST and swell below their LCST. Although temperature responsiveness is an important characteristic of synthetic polymers in drug and gene delivery, few studies have investigated the temperature-responsive catch and release of low-molecular-weight drugs (LMWDs) as their affinity to the target changes. Since LMWDs have only a few functional groups, preparation of NPs with high affinity for LMWDs is hard compared with that for peptides and proteins. However, LMWDs such as anticancer drugs often have a stronger effect than peptides and proteins. Therefore, the development of NPs that can load and release LMWDs is needed for drug delivery. Here, we engineered pNIPAm-based NPs that capture paclitaxel (PTX), an anticancer LMWD that inhibits microtubules, above their LCST and release it below their LCST. The swelling transition of the NPs depended on their hydrophobic monomer structure. NPs with swelling ratios (=NP size at 25 degrees C/NP size at 37 degrees C) exceeding 1.90 released captured PTX when cooled to below their LCST by changing the affinity for PTX. On the other hand, NPs with a swelling ratio of only 1.14 released melittin. Therefore, optimizing the functional monomers of temperature-responsive NPs is essential for the catch and release of the target in a temperature-dependent manner. These results can guide the design of stimuli-responsive polymers that catch and release their target molecules. CI - (c) 2023 The Authors. Published by American Chemical Society. FAU - Koide, Hiroyuki AU - Koide H AUID- ORCID: 0000-0003-1763-6593 AD - Department of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka, Shizuoka 422-8526, Japan. FAU - Yamaguchi, Kazuma AU - Yamaguchi K AD - Department of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka, Shizuoka 422-8526, Japan. FAU - Sato, Keijiro AU - Sato K AD - Department of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka, Shizuoka 422-8526, Japan. FAU - Aoshima, Maki AU - Aoshima M AD - Department of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka, Shizuoka 422-8526, Japan. FAU - Kanata, Shoko AU - Kanata S AD - Department of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka, Shizuoka 422-8526, Japan. FAU - Yonezawa, Sei AU - Yonezawa S AD - Department of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka, Shizuoka 422-8526, Japan. FAU - Asai, Tomohiro AU - Asai T AD - Department of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka, Shizuoka 422-8526, Japan. LA - eng PT - Journal Article DEP - 20231227 PL - United States TA - ACS Omega JT - ACS omega JID - 101691658 PMC - PMC10785788 COIS- The authors declare no competing financial interest. EDAT- 2024/01/15 06:42 MHDA- 2024/01/15 06:43 PMCR- 2023/12/27 CRDT- 2024/01/15 04:34 PHST- 2023/09/20 00:00 [received] PHST- 2023/12/11 00:00 [revised] PHST- 2023/12/13 00:00 [accepted] PHST- 2024/01/15 06:43 [medline] PHST- 2024/01/15 06:42 [pubmed] PHST- 2024/01/15 04:34 [entrez] PHST- 2023/12/27 00:00 [pmc-release] AID - 10.1021/acsomega.3c07226 [doi] PST - epublish SO - ACS Omega. 2023 Dec 27;9(1):1011-1019. doi: 10.1021/acsomega.3c07226. eCollection 2024 Jan 9.