PMID- 34370483 OWN - NLM STAT- MEDLINE DCOM- 20220127 LR - 20220127 IS - 1543-8392 (Electronic) IS - 1543-8384 (Linking) VI - 18 IP - 9 DP - 2021 Sep 6 TI - ERK-Peptide-Inhibitor-Modified Ferritin Enhanced the Therapeutic Effects of Paclitaxel in Cancer Cells and Spheroids. PG - 3365-3377 LID - 10.1021/acs.molpharmaceut.1c00303 [doi] AB - Rational design of a drug delivery system with enhanced therapeutic potency is critical for efficient tumor chemotherapy. Many protein-based drug delivery platforms have been designed to deliver drugs to target sites and improve the therapeutic efficacy. In this study, paclitaxel (PTX) molecules were encapsulated within an apoferritin nanocage-based drug delivery system with the modification of an extracellular-signal-regulated kinase (ERK) peptide inhibitor at the C-terminus of ferritin (HERK). Apoferritin is an endogenous nano-sized spherical protein which has the ability to specially bind to a majority of tumor cells via interacting with transferrin receptor 1. The ERK peptide inhibitor is a peptide which can disrupt the interaction of MEK with ERK in the mitogen-activated protein kinase/ERK pathway. By combining the targeted delivery effect of ferritin and the inhibitory effect of the ERK peptide inhibitor, the newly fabricated ferritin carrier nanoparticle HERK could still be taken up by tumor cells, and it displayed higher cell cytotoxicity than the parent ferritin. After loading with PTX, HERK-PTX displayed a favorable anticancer effect in human breast cancer cells MDA-MB-231 and lung carcinoma cells A549. The remarkable inhibitory effect on MDA-MB-231 tumor spheroids was also identified. These results indicated that the constructed HERK nanocarrier is a promising multi-functional drug delivery vehicle to enhance the therapeutic effect of drugs in cancer therapy. FAU - Dong, Yixin AU - Dong Y AUID- ORCID: 0000-0002-5898-9785 AD - College of Chemical Engineering, Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Jiangsu Provincial Key Laboratory for the Chemistry and Utilization of Agro-Forest Biomass, Jiangsu Key Laboratory of Biomass-Based Green Fuels and Chemicals, Nanjing Forestry University, Nanjing 210037, P. R. China. FAU - Ma, Yuanmeng AU - Ma Y AD - College of Chemical Engineering, Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Jiangsu Provincial Key Laboratory for the Chemistry and Utilization of Agro-Forest Biomass, Jiangsu Key Laboratory of Biomass-Based Green Fuels and Chemicals, Nanjing Forestry University, Nanjing 210037, P. R. China. FAU - Li, Xun AU - Li X AUID- ORCID: 0000-0002-1267-9263 AD - College of Chemical Engineering, Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Jiangsu Provincial Key Laboratory for the Chemistry and Utilization of Agro-Forest Biomass, Jiangsu Key Laboratory of Biomass-Based Green Fuels and Chemicals, Nanjing Forestry University, Nanjing 210037, P. R. China. FAU - Wang, Fei AU - Wang F AUID- ORCID: 0000-0001-6428-5111 AD - College of Chemical Engineering, Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Jiangsu Provincial Key Laboratory for the Chemistry and Utilization of Agro-Forest Biomass, Jiangsu Key Laboratory of Biomass-Based Green Fuels and Chemicals, Nanjing Forestry University, Nanjing 210037, P. R. China. FAU - Zhang, Yu AU - Zhang Y AUID- ORCID: 0000-0002-2614-5975 AD - College of Chemical Engineering, Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Jiangsu Provincial Key Laboratory for the Chemistry and Utilization of Agro-Forest Biomass, Jiangsu Key Laboratory of Biomass-Based Green Fuels and Chemicals, Nanjing Forestry University, Nanjing 210037, P. R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210809 PL - United States TA - Mol Pharm JT - Molecular pharmaceutics JID - 101197791 RN - 0 (Antineoplastic Agents) RN - 0 (Nanoparticle Drug Delivery System) RN - 0 (Peptides) RN - 0 (Protein Kinase Inhibitors) RN - 9007-73-2 (Ferritins) RN - 9013-31-4 (Apoferritins) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - P88XT4IS4D (Paclitaxel) SB - IM MH - Antineoplastic Agents/*administration & dosage/pharmacokinetics MH - Apoferritins/chemistry/pharmacology MH - Cell Line, Tumor MH - Drug Liberation MH - Drug Screening Assays, Antitumor MH - Drug Synergism MH - Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors MH - Ferritins/chemistry MH - Humans MH - Nanoparticle Drug Delivery System/chemistry/*pharmacology MH - Paclitaxel/*administration & dosage/pharmacokinetics MH - Peptides/chemistry/pharmacology MH - Protein Kinase Inhibitors/chemistry/pharmacology MH - Spheroids, Cellular OTO - NOTNLM OT - ERK peptide inhibitor OT - drug delivery OT - encapsulation OT - ferritin OT - paclitaxel EDAT- 2021/08/10 06:00 MHDA- 2022/01/28 06:00 CRDT- 2021/08/09 17:13 PHST- 2021/08/10 06:00 [pubmed] PHST- 2022/01/28 06:00 [medline] PHST- 2021/08/09 17:13 [entrez] AID - 10.1021/acs.molpharmaceut.1c00303 [doi] PST - ppublish SO - Mol Pharm. 2021 Sep 6;18(9):3365-3377. doi: 10.1021/acs.molpharmaceut.1c00303. Epub 2021 Aug 9.