生物活性聚合物作为刺激反应性抗转移联合药物治疗胰腺癌

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials Pub Date : 2025-03-13 DOI:10.1016/j.biomaterials.2025.123255

Sudipta Panja , Ekta Kapoor , Kasturi Siddhanta , Chinmay M. Jogdeo , Diptesh Sil , Rubayat I. Khan , Neha Kumari , Ling Ding , Howard E. Gendelman , Amar B. Singh , David Oupický

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引用次数: 0

摘要

胰腺导管腺癌（PDAC）的难治性和破坏性迫切需要新的治疗方法。本研究基于优化的抗转移大分子载体PCQ，结合吉西他滨（GEM），开发了一种用于PDAC联合治疗的新型聚合物前药系统。构效关系评价表明，与梯度PCQ类似物相比，随机PCQ共聚物具有更好的抗迁移活性。用二硫连接剂将GEM加入到随机PCQ共聚物中，制备还原响应前药PCQ(r)6-SS-GEM12。由此产生的治疗系统提出了一种药理学上活跃的递送策略，针对PDAC的增殖性和转移性表型。PCQ(r)6-SS-GEM12前药在肿瘤还原性环境下选择性释放GEM，从而显著抑制肿瘤生长，具有明显的抗转移作用。总的来说，我们的数据表明，抗转移性PCQ和基于细胞毒性gem的还原反应前药聚合物的结合为治疗PDAC提供了一种创新的策略。

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Bioactive polymers as stimulus-responsive anti-metastatic combination agents to treat pancreatic cancer

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Bioactive polymers as stimulus-responsive anti-metastatic combination agents to treat pancreatic cancer

The intractable and devastating nature of pancreatic ductal adenocarcinoma (PDAC) necessitates an urgent need for novel therapies. This study presents the development of a novel polymer prodrug system for the combination treatment of PDAC, based on an optimized pharmacologically active anti-metastatic macromolecular carrier, PCQ, conjugated with gemcitabine (GEM). Structure-activity relationship evaluations showed that random PCQ copolymers exhibited superior anti-migratory activity compared to the gradient PCQ analogs. GEM was incorporated into the random PCQ copolymers using disulfide linker to prepare a reduction-responsive prodrug, PCQ(r)6-SS-GEM12. The resultant therapeutic system presents a pharmacologically active delivery strategy that targets both the proliferative and the metastatic phenotype in PDAC. The PCQ(r)6-SS-GEM12 prodrug demonstrated a selective release of GEM under the reductive tumor environment leading to a significant inhibition of tumor growth with pronounced anti-metastatic effect. Collectively, our data show that the combination of anti-metastatic PCQ and cytotoxic GEM-based reduction-responsive prodrug polymer offers an innovative strategy to treat PDAC.

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来源期刊

Biomaterials 工程技术-材料科学：生物材料

CiteScore

26.00

自引率

2.90%

发文量

565

审稿时长

46 days

期刊介绍： Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.