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·1332· 精细化工 FINE CHEMICALS 第 36 卷
温度低于 32 ℃时 D h 基本保持在 120 nm 左右，当 的胶束。
温度高于 32 ℃后 D h 随温度升高逐渐减小至 93 nm （3）利用 HRP/ H 2 O 2 催化交联 P(4-VPh)胶束核
左右。随着温度升高，核交联胶束壳层的 PNIPAm 制备了酶催化核交联的 P(4-VPh-b-NIPAm)胶束，
刷逐步脱水坍塌导致粒径减小。P(4-VPh-b-NIPAm) 25 ℃时平均粒径约为 119 nm，在水中具有极好的稳
和核交联胶束 37 ℃时的粒径分布如图 7b 所示， 定性，其水溶液的 LCST 为 34.9 ℃，随温度升高其
37 ℃时 P(4-VPh-b-NIPAm)水溶液呈现出宽的多重 粒径逐渐减小至 37 ℃的 92.9 nm，表现出良好的温
粒径分布。这是因为温度高于 LCST 后，P(4-VPh-b- 度响应和热稳定性。该酶催化交联胶束可在核交联
NIPAm)转变成全疏水聚合物，自组装形成的胶束解 的同时实现药物的装载，可望应用于疏水药物温度
体，在水中形成不稳定的大尺寸聚集体甚至沉淀。 响应的控制释放。
而核交联胶束 37 ℃时仍为单峰分布（D h ≈92.9 nm，
参考文献：
PDI=0.217）。虽然在 37 ℃时核交联胶束壳层的
PNIPAm 已转变成疏水链段，但是相邻 PNIPAm 刷 [1] Cabral H, Miyata K, Osada K, et al. Block copolymer micelles in
nanomedicine applications[J]. Chemical Review, 2018, 118 (14):
间的排斥效应与体积位阻会阻碍 PNIPAm 大分子链
6844-6892.
在胶束核表面的完全坍塌，使得核交联胶束在水中 [2] Biswas S, Kumari P, Lakhani P, et al. Recent advances in polymeric
仍保持稳定。 micelles for anti-cancer drug delivery[J]. European Journal of
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[3] Kuang H, Wu S, Meng F, et al. Core-crosslinked amphiphilic
biodegradable copolymer based on the complementary multiple
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micelles: principles, preparation, biomedical applications and clinical
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[8] Talelli M, Iman M, Varkouhi A K, et al. Core-crosslinked polymeric
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[9] Piogé S, Nesterenko A, Brotons G, et al. Core cross-linking of
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图 7 核交联胶束的 D h 随温度的变化（a）；P(4-VPh-b- Macromolecules, 2011, 44(3): 594-603.
[10] Chen J, Ouyang J, Kong J, et al. Photo-cross-linked and pH-sensitive
NIPAm)和核交联胶束 37 ℃时的粒径分布（b）
biodegradable micelles for doxorubicin delivery[J]. ACS Applied
Fig. 7 (a) D h of core-crosslinked micelles as a function of
temperature, (b) size distribution of P(4-VPh-b-NIPAm) Materials & Interfaces, 2013, 5 (8): 3108-3117.
micelles and core-crosslinked micelles at 37 ℃ [11] Dai Y, Chen X, Zhang X, et al. Recent developments in the area of
click-crosslinked nanocarriers for drug delivery[J]. Macromolecular
Rapid Communications, 2019, 40(3): 1800541.
3 结论 [12] Gu Z, Wang X, Cheng R, et al. Hyaluronic acid shell and
disulfide-crosslinked core micelles for in vivo targeted delivery of
（1）通过 RAFT 聚合合成了结构明确、窄相对 bortezomib for the treatment of multiple myeloma[J]. Acta
分子质量分布的 P(4-ASt-b-NIPAm)两嵌段共聚物， Biomaterialia, 2018, 80: 288-295.
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再经水合肼选择性水解制备了 P(4-VPh-b-NIPAm)两
for pH and reduction dual-responsive triggered DOX delivery[J].
亲性聚合物。 International Journal of Biological Macromolecules, 2019, 123:
（ 2） P(4-VPh-b-NIPAm) 水溶 液的 LCST 为 1150-1156.
31.2 ℃，CMC 为 0.015 g/L，可形成平均粒径为 137 nm [14] Kawakita H, Hamamoto K, Ohto K, et al. Polyphenol polymerization
