Department of Chemistry, Laboratory for Organic Synthesis of Functional Systems, Humboldt-Universität zu Berlin, Brook-Taylor-Str. 2, D-12489 Berlin, Germany.
Biomacromolecules. 2021 Jan 11;22(1):213-221. doi: 10.1021/acs.biomac.0c01284. Epub 2020 Nov 23.
Tailor-made copolymers are designed based on a peptide-poly(ethylene glycol) (QFFLFFQ-PEG) conjugate as a blueprint, to solubilize the photosensitizer -tetra(hydroxyphenyl)chlorin (-THPC). The relevant functionalities of the parent peptide-PEG are mimicked by employing monomer pairs that copolymerize in a strictly alternating manner. While styrene (S) or 4-vinylbenzyl-phthalimide (VBP) provide aromatic moieties like Phe, the aliphatic isobutyl side chain of Leu4 is mimicked by maleic anhydride (MA) that reacts after polymerization with isobutylamine to give the isobutylamide-carboxyl functional unit (iBuMA). A set of copolymer-PEG solubilizers is synthesized by controlled radical polymerization, systematically altering the length of the functional segment (DP = 2, 4, 6) and the side chain functionalization (iBuMA, iPrMA, MeMA). The -THPC hosting and release properties of P[S--iBuMA]-PEG reached higher payload capacities and more favored release rates than the parent peptide-PEG conjugate. Interestingly, P[SRMA]-PEG mimics the sensitivity of the peptide-PEG solubilizer well, where the exchange of Leu4 residue by Val and Ala significantly reduces the drug loading by 92%. A similar trend is found with P[SRMA]-PEG as the exchange of iBu → iPr → Me reduces the payload capacity up to 78%.
定制共聚物是基于肽-聚乙二醇（QFFLFFQ-PEG）缀合物设计的，用于溶解光敏剂-四（对羟苯基）氯（-THPC）。通过采用严格交替共聚的单体对模拟母体肽-PEG 的相关功能。苯乙烯（S）或 4-乙烯基苯并邻苯二甲酰亚胺（VBP）提供类似 Phe 的芳族部分，而马来酸酐（MA）模拟 Leu4 的脂族异丁基侧链，聚合后与异丁胺反应得到异丁酰胺-羧基功能单元（iBuMA）。通过受控自由基聚合合成了一系列共聚物-PEG 增溶剂，系统地改变功能段的长度（DP=2、4、6）和侧链官能化（iBuMA、iPrMA、MeMA）。与母体肽-PEG 缀合物相比，-THPC 承载和释放性能的 P[S--iBuMA]-PEG 达到了更高的载药能力和更有利的释放速率。有趣的是，P[SRMA]-PEG 很好地模拟了肽-PEG 增溶剂的敏感性，其中 Leu4 残基被 Val 和 Ala 取代会使药物负载降低 92%。在 P[SRMA]-PEG 中也发现了类似的趋势，当 iBu→iPr→Me 取代时，载药能力降低了 78%。
