Synthesis and evaluation of peptide-mimetic anti-cancer nanoparticles

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K18380
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 90120:Biomaterials-related
• Research Institution: Hiroshima University
• Principal Investigator: Takahashi Haruko 広島大学, 統合生命科学研究科(理), 助教 (70775767)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 抗がん性ポリマー / ドーマント / がん微小環境

Outline of Final Research Achievements

The discovery of anti-cancer agents effective against non-proliferative dormant cancer cells is a significant challenge in cancer biology and drug development fields because currently used drugs target only actively proliferating cancer cells. We have developed new anti-cancer polymers that mimic the mode of action of host-defense peptides (HDPs) with anticancer activity. These polymers are synthetic methacrylate polymers with cationic and amphiphilic properties to recapitulate the biophysical traits of the HDPs. We designed the polymer compositions and structures to target highly expressed anionic lipids exposed on the cancer cells and act by disrupting the integrity of cancer cell membranes, causing cell death. Because this mechanism is not dependent on cell proliferation, our polymers have shown potent activity against dormant cancer cells and in vitro 3D tumor models. Our new polymer design approach has paved the way for discovery of novel anti-cancer therapeutics.

Free Research Field

バイオマテリアル

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、生体のペプチドを模倣することより、「固形がんの深部まで到達可能」で、固形がん内の「休眠状態(ドーマント)のがんにも有効」な新しい抗がん性ポリマーの設計指針を確立した。この抗がん性ポリマーは、従来の抗がん薬とは異なり、がん細胞膜にアタックする機構を利用した、ポリマーならではの機能を利用した次世代の抗がん性マテリアルとして高いポテンシャルが期待できる。これにより、これまで治療の難しかった固形がん中のドーマントながん細胞に対する、新しいアプローチ法を提案することができた。