Modification of α-Cyclodextrin Polyrotaxanes by ATRP for Conjugating Drug and Prolonging Blood Circulation

Zhang, Jialiang; Zhang, Ling’e; Li, Shun; Yin, Changfeng; Li, Cheng; Wu, Wei; Jiang, Xiqun

doi:10.1021/acsbiomaterials.7b00464

Cited by 18 publications

(11 citation statements)

References 26 publications

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“…is about 762.3 ± 53.6 and 226.7 ± 95.1 ng/mL, respectively, which is 2 times higher than that of free PTX (342.2 ± 117.2 and 123.6 ± 14.7 ng/mL at 1 and 12 h p.i., respectively). Commonly, the blood circulation half-life for free PTX in a mouse model is in tens of minutes. , Notably, the blood sampling reveals a significantly longer circulation time for PRNP than free PTX.…”

Section: Resultsmentioning

confidence: 99%

Therapy for Gastric Cancer with Peritoneal Metastasis Using Injectable Albumin Hydrogel Hybridized with Paclitaxel-Loaded Red Blood Cell Membrane Nanoparticles

Qian

Cai

et al. 2019

ACS Biomater. Sci. Eng.

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The local delivery of therapeutics in a long-term sustained manner at tumor sites is attractive for the therapy of gastric cancer with peritoneal metastasis. In this manuscript, an injectable hydrogel-encapsulating paclitaxel-loaded red blood cell membrane nanoparticles (PRNP-gel) is designed on the basis of temperature-induced phase transition of polyethylene-glycol-modified bovine serum albumin (PEG-BSA). Dynamic light scattering, ζ potential, and electron microscopy were utilized to characterize the nanoparticle–hydrogel hybrid system. It was found that the PRNP had a spherical morphology with a diameter of about 133 nm and negative surface potential. The drug loading efficiency and loading content are 85% and 22%, respectively. In situ gelation occurred within 12 min when the gel precursor was incubated at 37 °C or injected subcutaneously. The in-situ-forming hydrogel showed a sustained release profile, and the cumulative release of PTX was ∼30% after 6 days. The PRNP-gel exhibited high cytocompatibility and biodegradability in vitro and in vivo. This nanoparticle–hydrogel hybrid system is applied as a drug carrier for local chemotherapy to enhance therapeutic levels at tumor site and reduce the systemic toxicity. In vivo antitumor evaluation within a subcutaneous xenograft and peritoneal dissemination model showed that the hydrogel possesses good tumor growth suppression properties after a single injection. Hence, the as-prepared injectable hydrogel system could be a promising candidate for the local delivery of chemotherapeutic drugs.

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Section: Resultsmentioning

confidence: 99%

Therapy for Gastric Cancer with Peritoneal Metastasis Using Injectable Albumin Hydrogel Hybridized with Paclitaxel-Loaded Red Blood Cell Membrane Nanoparticles

Qian

Cai

et al. 2019

ACS Biomater. Sci. Eng.

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“…对 PR 中的 CD 进行高分子聚合物修饰, 不仅能提高 PR 的水溶性, 而且能够有效提高药物的负载量及其细胞相容性等 [34,79～82] . 例如 Jiang 等 [81] 采用 ATRP 法对 PR 中的 CD 进行改性, 分别接枝上聚甲基丙烯酸-2-羟乙酯(PHEMA)和正丁酯保护的聚甲基丙烯酸甜菜碱 (PCB-tBu), 制备得到水溶性 PR. 其中 PHEMA 多臂聚合物能与抗癌药物紫杉醇(PTX)结合, 负载量达 6.6%, 外层的 PCB 链段则具有优异的亲水性, 血液循环实验表明该体系具有非常优越的缓释能力.…”

Section: 环糊精聚合在生物医学中的应用unclassified

Advances in Cyclodextrin Polymers and Their Applications in Biomedicine

Qie¹,

Hao²,

Liu³

et al. 2020

Acta Chim. Sinica

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Cyclodextrins (CDs) are a family of macrocyclic oligosaccharides composed of α-1,4-linked D-glucopyranose units. The most commonly used CDs are α-, β-, and γ-CD, which consist of 6, 7, and 8 D-glucose units, respectively. They possess a relative hydrophobic inner cavity and a hydrophilic outer surface and can form inclusion complexes with various small molecules, metal ions and polymers, tailoring the physicochemical property of the guests, and thus have been widely used in the fields of pharmacy, food, chemistry, chromatography, catalysis, biotechnology, agriculture, cosmetics, hygiene, medicine, textiles and the environment, etc. However, it is difficult to manipulate the native CDs in some specific applications, they are crystallized solid and soluble in water but insoluble in most organic solvents. CD polymers (CDPs), such as crosslinked CDs or CD based hydrogels with various crosslinkers by chemical reactions, and CD based supramolecular polymers formed by physical interactions, can achieve the integration effect and synergy effect of CDs, crosslinkers and guest polymers, not only possessing the inclusion capacity of CDs, but also endowing CDs with other properties introduced by crosslinkers. The CDPs can be easily manipulated and they exhibit unique features that native CDs are lack of. Hence, the design, synthesis and applications of CDPs have attracted broad interests in recent years. This review focuses on the recent progress in CDPs, and different types of CDPs are identified and classified based on the structures and functions, namely CD based polyrotaxane, grafted CDs, crosslinked CDs and linear CDs, etc. Besides, the synthetic methodologies of CDPs are highlighted. Particular attention is paid to the breakthrough on the CDPs in the past five years, and their applications in biomedicine, such as drug delivery, gene delivery, target delivery, controlled release and cell imaging are discussed in detail. The typical applications in other fields such as absorption, environment remediation, thermal insulation, catalysis and slid-ring gels are also discussed in brief. Finally, the review provides brief summary and prospect of CDPs. Keywords cyclodextrin; polymer; chemical crosslinking; drug carrier; supramolecular self-assembly 1 引言环糊精(cyclodextrin, 简称 CD)是一类由吡喃葡萄糖单元通过 α-1,4-糖苷键链接而成的大环分子, 具有疏水空腔和亲水外壁的中空圆台状立体结构, 能够通过包结作用(encapsulation)与多种小分子和聚合物形成主-客体(host-guest)包结物(inclusion complexes), 从而实现对客体分子物理和化学性能的调控, 被广泛用于制药、食

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“…It is also necessary to point out the recent advance for PRX mediated delivery in vivo, i.e. zwitterionic poly(carboxybetaine) grafted PRX for paclitaxel delivery [60] poly(ethylenimine)-grafted PRX functionalized with folate for tumor targeting delivery [61] and β-cyclodextrin-based polyrotaxane for cancer theranostics [62]. This valuable information could be complementary to our discovery to enrich the growing list of the design features of PRX.…”

Section: Pil-12 Laden 4-arm Prx Improved Toxicity Profiles In Mice Compared To Ril-12mentioning

confidence: 99%

Development of self-assembled multi-arm polyrotaxanes nanocarriers for systemic plasmid delivery in vivo

Liu

Huang

et al. 2019

Biomaterials

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Polyrotaxane (PRX) is a promising supramolecular carrier for gene delivery. Classic PRX exhibits a linear structure in which the amine-functionalized α-cyclodextrin (CD) is threaded along the entire polyethylene glycol (PEG) backbone. While promising in vitro, the absence of free PEG moieties after CD threading compromised the in vivo implementation, due to the unfavorable pharmacokinetics (PK) and biodistribution profile. Herein, we developed a multi-arm PRX nanocarrier platform, which has been designed for protective nucleic acid encapsulation, augmented biodistribution and PK, and suitable for intravenous (IV) administration. A key design was to introduce cationic CD rings onto a multi-arm PEG backbone in a spatially selective fashion. The optimal structural design was obtained through iterative rounds of experimentation to determine the appropriate type and density of cationic charge on CD ring, the degree of PEGylation, the size and structure of polymer backbone, etc. This allowed us to effectively deliver large size reporter and therapeutic plasmids in cancer mouse models. Post IV injection, we demonstrated that our multi-arm polymer design significantly enhanced circulatory half-life and PK profile compared to the linear PRX. We continued to use the multi-arm PRX to formulate a therapeutic plasmid encoding an immunomodulatory cytokine, IL-12. When tested in a colon cancer syngeneic mouse model with same background, the IL-12 plasmid was protected by the multi-arm PRX and delivered through the tail vein to the tumor site, leading to a significant tumor inhibition effect. Moreover, our delivery system was devoid of major systemic toxicity.

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Modification of α-Cyclodextrin Polyrotaxanes by ATRP for Conjugating Drug and Prolonging Blood Circulation

Cited by 18 publications

References 26 publications

Therapy for Gastric Cancer with Peritoneal Metastasis Using Injectable Albumin Hydrogel Hybridized with Paclitaxel-Loaded Red Blood Cell Membrane Nanoparticles

Therapy for Gastric Cancer with Peritoneal Metastasis Using Injectable Albumin Hydrogel Hybridized with Paclitaxel-Loaded Red Blood Cell Membrane Nanoparticles

Advances in Cyclodextrin Polymers and Their Applications in Biomedicine

Development of self-assembled multi-arm polyrotaxanes nanocarriers for systemic plasmid delivery in vivo

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