PMID- 33949615 OWN - NLM STAT- MEDLINE DCOM- 20210816 LR - 20210816 IS - 2050-7518 (Electronic) IS - 2050-750X (Linking) VI - 9 IP - 19 DP - 2021 May 19 TI - A carrier-free nanoparticle with dual NIR/acid responsiveness by co-assembly of enediyne and IR820 for combined PTT/chemotherapy. PG - 4056-4064 LID - 10.1039/d1tb00279a [doi] AB - Combined photothermal therapy/chemotherapy by co-delivery of a photosensitizer (PS) and a chemotherapeutic drug has demonstrated great potential for cancer treatment. The intrinsic drawbacks of traditional drug delivery systems (DDSs), such as tedious synthetic procedures, side effects originated from the carrier materials, low loading efficiency, and uncontrolled drug release, however, have impaired their further advancement. On the other hand, enediyne antibiotics are highly cytotoxic toward cancer cells through the generation of lethal carbon radicals via thermal-induced cyclization, endowing them with great potential to achieve enhanced synergistic anticancer performance by incorporation with the photothermal effect of PS. To this end, a carrier-free and NIR/acid dual-responsive DDS was constructed for combined photothermal therapy/chemotherapy. The facile co-assembly of maleimide-based enediyne and PS IR820 was achieved in aqueous solution to give nanoparticles (EICN) with a hydrodynamic diameter of 90 nm and high stability. In vitro study confirmed the acid/NIR dual-responsive degradation and drug release, free radical generation and DNA-cleaving ability of EICN, which was accomplished by the corporation of enediyne and IR820 moieties. Further tests on HeLa cells verified the excellent synergistic anticancer performance of EICN including the improved cellular uptake, NIR-enhanced drug release, DNA damage and histone deacetylase inhibitor capacity. Overall, this carrier-free DDS with dual acid/NIR-responsivity would potentially provide new insights for the development of combined photothermal/chemotherapy. FAU - Lu, Haotian AU - Lu H AD - Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China. xinxinli@ecust.edu.cn hagmhsn@ecust.edu.cn. FAU - Wang, Wenbo AU - Wang W AD - Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China. xinxinli@ecust.edu.cn hagmhsn@ecust.edu.cn. FAU - Li, Xiaoxuan AU - Li X AD - Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China. xinxinli@ecust.edu.cn hagmhsn@ecust.edu.cn. FAU - Zhang, Mengsi AU - Zhang M AD - Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China. xinxinli@ecust.edu.cn hagmhsn@ecust.edu.cn. FAU - Cheng, Xiaoyu AU - Cheng X AD - Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China. xinxinli@ecust.edu.cn hagmhsn@ecust.edu.cn. FAU - Sun, Ke AU - Sun K AD - Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China. xinxinli@ecust.edu.cn hagmhsn@ecust.edu.cn. FAU - Ding, Yun AU - Ding Y AUID- ORCID: 0000-0002-7012-5621 AD - Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China. xinxinli@ecust.edu.cn hagmhsn@ecust.edu.cn. FAU - Li, Xinxin AU - Li X AD - Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China. xinxinli@ecust.edu.cn hagmhsn@ecust.edu.cn. FAU - Hu, Aiguo AU - Hu A AUID- ORCID: 0000-0003-0456-7269 AD - Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China. xinxinli@ecust.edu.cn hagmhsn@ecust.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Mater Chem B JT - Journal of materials chemistry. B JID - 101598493 RN - 0 (Antineoplastic Agents) RN - 0 (Drug Carriers) RN - 0 (Enediynes) RN - 0 (IR 820) RN - 0 (Photosensitizing Agents) RN - 17778-80-2 (Singlet Oxygen) RN - IX6J1063HV (Indocyanine Green) SB - IM MH - Antineoplastic Agents/*chemistry/metabolism/pharmacology/therapeutic use MH - Apoptosis/drug effects MH - DNA Cleavage/drug effects MH - Drug Carriers/chemistry MH - Drug Liberation MH - Enediynes/*chemistry MH - HeLa Cells MH - Humans MH - Hydrogen-Ion Concentration MH - Hyperthermia, Induced MH - Indocyanine Green/*analogs & derivatives/chemistry MH - *Infrared Rays MH - Nanoparticles/*chemistry MH - Neoplasms/drug therapy/therapy MH - Particle Size MH - Photosensitizing Agents/chemistry/metabolism/pharmacology/therapeutic use MH - Phototherapy MH - Singlet Oxygen/chemistry/metabolism EDAT- 2021/05/06 06:00 MHDA- 2021/08/17 06:00 CRDT- 2021/05/05 09:12 PHST- 2021/05/06 06:00 [pubmed] PHST- 2021/08/17 06:00 [medline] PHST- 2021/05/05 09:12 [entrez] AID - 10.1039/d1tb00279a [doi] PST - ppublish SO - J Mater Chem B. 2021 May 19;9(19):4056-4064. doi: 10.1039/d1tb00279a.