Telomere　length　plays　a　crucial　role　in　cellular　aging　and　the　risk　of　diseases.　Unlike　normal　cells,　cancer　cells　can　extend　their　own　survival　by　maintaining　telomere　stability　through　telomere　maintenance　mechanism.　Therefore,　regulating　the　lengths　of　telomeres　have　emerged　as　a　promising　approach　for　anti-cancer　treatment.　In　this　study,　we　introduce　a　nanoscale　octopus-like　structure　designed　to　induce　physical　entangling　of　telomere,　thereby　efficiently　triggering　telomere　dysfunction.　The　nanoscale　octopus,　composed　of　eight-armed　PEG　(8-arm-PEG),　are　functionalized　with　cell　penetrating　peptide　(TAT)　to　facilitate　nuclear　entry　and　are　covalently　bound　to　N-Methyl　Mesoporphyrin　IX　(NMM)　to　target　G-quadruplexes　(G4s)　present　in　telomeres.　The　multi-armed　configuration　of　the　nanoscale　octopus　enables　targeted　binding　to　multiple　G4s,　physically　disrupting　and　entangling　numerous　telomeres,　thereby　triggering　telomere　dysfunction.　Both　in　vitro　and　in　vivo　experiments　indicate　that　the　nanoscale　octopus　significantly　inhibits　cancer　cell　proliferation,　induces　apoptosis　through　telomere　entanglement,　and　ultimately　suppresses　tumor　growth.　This　research　offers　a　novel　perspective　for　the　development　of　innovative　anti-cancer　interventions　and　provides　potential　therapeutic　options　for　targeting　telomeres.　©　2024　Elsevier　Ltd