Jump to main content
Jump to site search
Access to RSC content Close the message box

Continue to access RSC content when you are not at your institution. Follow our step-by-step guide.


Issue 15, 2020
Previous Article Next Article

Synthesis of cyclic graft polymeric prodrugs with heterogeneous grafts of hydrophilic OEG and reducibly conjugated CPT for controlled release

Author affiliations

Abstract

Fabrication of cyclic graft (cg) copolymer-based polymeric prodrugs by conjugation of drug molecules to cg copolymers via a dynamic covalent bond capable of responding to biorelevant signals integrates simultaneously the merits of cg copolymers and polymeric prodrugs for enhanced stability of nanocarriers and precise modulation of drug release kinetics. To completely eliminate the compromised drug conjugation efficiency due to the steric hindrance of hydrophilic grafts, it will be useful to develop cg polymeric prodrugs with heterogeneous grafts composed of hydrophilic polymers and drug species, respectively. For this purpose, we reported in this study the synthesis of cyclic graft polymeric prodrugs with heterogeneous grafts of hydrophilic oligo (ethylene glycol) (OEG) and reducibly conjugated camptothecin (CPT), cg-poly(oligo(ethylene glycol) monomethyl ether methacrylate)-b-poly((2-hydroxyethyl methacrylate)-disulfide link-camptothecin) (cg-P(OEGMA)-b-P(HEMA-SS-CPT), cg-prodrugs), via an integrated strategy of a previously reported diblock copolymer-based template and post-polymerization intermolecular click conjugation of a reducible CPT prodrug. The micelles self-assembled from cg-prodrugs on one hand had sufficient salt stability due to the branched cg structure, and on the other hand showed a reduction-triggered cleavage of the disulfide link for a promoted CPT release. Most importantly, we uncovered two interesting phenomena of the cg-based polymeric prodrugs as delivery vehicles: (i) the dimensions of both self-assemblies formed by the cg and bottlegraft (bg) polymers depend substantially on the molecular size of the cg and bg polymers likely due to the steric hindrance of the grafted structures of the cg and bg molecules and relatively low aggregation number of the self-assembled structures, and (ii) cg-prodrug-based micelles exhibited greater in vitro cytotoxicity against cancer cells despite the lower drug loading content (DLC) than the bg-based analogues, which results primarily from the faster reduction-triggered degradation and drug release as well as the greater cellular uptake efficiency of the former micelle prodrugs. Taken together, the developed cg-prodrugs provide great potential for chemotherapy, and the aforementioned interesting results will definitely inspire more upcoming studies on the future design and development of novel cg polymers for biomedical applications.

Graphical abstract: Synthesis of cyclic graft polymeric prodrugs with heterogeneous grafts of hydrophilic OEG and reducibly conjugated CPT for controlled release

Back to tab navigation

Supplementary files

Article information


Submitted
25 Apr 2020
Accepted
02 Jun 2020
First published
03 Jun 2020

Biomater. Sci., 2020,8, 4206-4215
Article type
Paper

Synthesis of cyclic graft polymeric prodrugs with heterogeneous grafts of hydrophilic OEG and reducibly conjugated CPT for controlled release

C. Meng, Y. Cao, L. Sun, Y. Liu, G. Kang, W. Ma, J. Peng, K. Deng, L. Ma and H. Wei, Biomater. Sci., 2020, 8, 4206
DOI: 10.1039/D0BM00656D

Social activity

Search articles by author

Spotlight

Advertisements