The impact of PEG chain length on the in vivo tumor accumulation of self-assembled amphiphilic drug-PEG polymeric micelles Journal Article
| Authors: | Zheng, M.; Mei, T.; Deng, C.; Xin, J.; Aras, O.; An, F.; Chen, N. |
| Article Title: | The impact of PEG chain length on the in vivo tumor accumulation of self-assembled amphiphilic drug-PEG polymeric micelles |
| Abstract: | The integration of a drug and polyethylene glycol (PEG) into an amphiphilic polymer to form self-assembled micelles with high drug loading for self-delivery to tumors is recently reported, which has showed high clinical availability. However, the effect of PEG chain length on cell internalization efficiency and tumor targeting efficiency in this PEG-drug conjugate micelle self-delivery system has yet to be studied. Herein, pyropheophorbide-a (PhA) was used as a model drug and a fluorescent tracer to synthesize amphiphilic polymers with varying PEG chain lengths, which self-assembled into PhA-PEG2000 NPs and PhA-PEG5000 NPs with high drug loading (21.2% and 9.7%, respectively, according to calculation). The results showed that PhA-PEG2000 NPs had higher cell internalization in vitro than PhA-PEG5000 NPs, but much lower tumor accumulation in vivo than PhA-PEG5000 NPs. This was attributed to the longer in vivo blood circulation time of the latter. Furthermore, the in vitro and in vivo examinations revealed negligible side effects, indicating the intrinsic safety of the micelles. This study provides insight into the influence of PEG chain length on biodistribution of organs and tumor accumulation after intravenous administration of PEG-drug conjugate micelle and guides the design of drug incorporated amphiphilic polymer-based micelles. © 2023 Elsevier B.V. |
| Keywords: | controlled study; unclassified drug; human cell; nonhuman; flow cytometry; neoplasm; mouse; fluorescent dye; animal experiment; animal model; in vivo study; in vitro study; drug synthesis; cell culture; blood sampling; tumors; quantitative analysis; cardiovascular system; polymerization; in-vivo; fluorescence microscopy; matrix assisted laser desorption ionization time of flight mass spectrometry; molecular weight; macrogol; particle size; chain length; polyethylene glycols; fluorescence imaging; proton nuclear magnetic resonance; blood examination; efficiency; transmission electron microscopy; targeted drug delivery; critical micelle concentration; amphophile; micelle; micelles; polyethylenes; controlled drug delivery; fluorescence intensity; polyethylene glycol; cell internalization; human; female; article; hela cell line; tumor accumulation; photon correlation spectroscopy; internalization (cell); balb/c nude mouse; drug-conjugates; blood biochemistry; peg chain length; pyropheophorbide a; self assembled nanoparticle; amphiphilic polymers; glycols chain length; high drug loadings; polyethylene glycol chain length; kunming mouse |
| Journal Title: | Colloids and Surfaces A: Physicochemical and Engineering Aspects |
| Volume: | 682 |
| ISSN: | 0927-7757 |
| Publisher: | Elsevier B.V. |
| Date Published: | 2024-02-05 |
| Start Page: | 132823 |
| Language: | English |
| DOI: | 10.1016/j.colsurfa.2023.132823 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Source: Scopus |
