PMID- 37321227 OWN - NLM STAT- MEDLINE DCOM- 20230626 LR - 20240103 IS - 1748-605X (Electronic) IS - 1748-6041 (Linking) VI - 18 IP - 4 DP - 2023 Jun 23 TI - Optimized silk fibroin nanoparticle functionalization with anti-CEA nanobody enhancing active targeting of colorectal cancer cells. LID - 10.1088/1748-605X/acdeba [doi] AB - This work aimed to establish a simple and feasible method to obtain silk fibroin nanoparticles (SFNPs) with uniform particles size, and then modify the SFNPs with nanobody (Nb) 11C12 targeting the proximal membrane end of carcinoembryonic antigen on the surface of colorectal cancer (CRC) cells. The regenerated silk fibroin (SF) was isolated using ultrafiltration tubes with a 50 kDa molecular weight cut-off, and the retention fraction (named as SF > 50 kDa) was further self-assembled into SFNPs by ethanol induction. Scanning electron microscope (SEM) and high-resolution transmission electron microscop showed that the SFNPs with uniform particles size were formed. Due to electrostatic adsorption and pH responsiveness, SFNPs have been proved to effectively load and release the anticancer drug doxorubicin hydrochloride (DOX) (DOX@SFNPs). Further, targeting molecule Nb 11C12 was used to modify these nanoparticles, constituting the targeted outer layer of the drug delivery system (DOX@SFNPs-11C12), achieving precise localization to cancer cells. The release amount of DOX observed fromin vitrodrug release profiles increased as follows: pH 7.4 < pH 6.8 < pH 5.4, demonstrating that the DOX release could be accelerated in a weakly acidic environment.In vitrocytotoxicity experiments displayed that SFNPs-11C12 nanoparticles exhibited good safety and biocompatibility. Drug-loaded nanoparticles, DOX@SFNPs-11C12, led to higher LoVo cells apoptosis compared to DOX@SFNPs. Fluorescence spectrophotometer characterization and confocal laser scanning microscopy further showed that the internalization of DOX was highest in the DOX@SFNPs-11C12, certifying that the introduced targeting molecule enhanced the uptake of drug delivery system by LoVo cells. This study provides a simple and operational approach to developing an optimized SFNPs drug delivery system modified by targeting Nb, which can be a good candidate for CRC therapy. CI - (c) 2023 IOP Publishing Ltd. FAU - Fan, Xiying AU - Fan X AUID- ORCID: 0000-0002-4041-9725 AD - CAS Key Laboratory of Biobased Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, People's Republic of China. AD - Shandong Energy Institute, Qingdao 266101, People's Republic of China. AD - Qingdao New Energy Shandong Laboratory, Qingdao 266101, People's Republic of China. FAU - Peng, Xinying AU - Peng X AD - CAS Key Laboratory of Biobased Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, People's Republic of China. AD - University of Chinese Academy of Sciences, No. 19(A) Yuquan Road, Beijing 100049, People's Republic of China. FAU - Wang, Tingting AU - Wang T AD - CAS Key Laboratory of Biobased Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, People's Republic of China. AD - Shandong Energy Institute, Qingdao 266101, People's Republic of China. AD - Qingdao New Energy Shandong Laboratory, Qingdao 266101, People's Republic of China. FAU - Gu, Yi AU - Gu Y AD - CAS Key Laboratory of Biobased Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, People's Republic of China. AD - University of Chinese Academy of Sciences, No. 19(A) Yuquan Road, Beijing 100049, People's Republic of China. FAU - Sun, Guochuan AU - Sun G AD - CAS Key Laboratory of Biobased Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, People's Republic of China. AD - Shandong Energy Institute, Qingdao 266101, People's Republic of China. AD - Qingdao New Energy Shandong Laboratory, Qingdao 266101, People's Republic of China. FAU - Shou, Qinghui AU - Shou Q AD - CAS Key Laboratory of Biobased Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, People's Republic of China. AD - Shandong Energy Institute, Qingdao 266101, People's Republic of China. AD - Qingdao New Energy Shandong Laboratory, Qingdao 266101, People's Republic of China. FAU - Song, Haipeng AU - Song H AD - Shenzhen Innova Nanobodi Co., Ltd, No. 1301 Guanguang Road, Shenzhen 518110, People's Republic of China. FAU - Nian, Rui AU - Nian R AD - CAS Key Laboratory of Biobased Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, People's Republic of China. AD - Shandong Energy Institute, Qingdao 266101, People's Republic of China. AD - Qingdao New Energy Shandong Laboratory, Qingdao 266101, People's Republic of China. FAU - Liu, Wenshuai AU - Liu W AD - CAS Key Laboratory of Biobased Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, People's Republic of China. AD - Shandong Energy Institute, Qingdao 266101, People's Republic of China. AD - Qingdao New Energy Shandong Laboratory, Qingdao 266101, People's Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230623 PL - England TA - Biomed Mater JT - Biomedical materials (Bristol, England) JID - 101285195 RN - 9007-76-5 (Fibroins) RN - 0 (Carcinoembryonic Antigen) RN - 0 (Antineoplastic Agents) RN - 80168379AG (Doxorubicin) SB - IM MH - Humans MH - *Fibroins/chemistry MH - Carcinoembryonic Antigen MH - *Antineoplastic Agents MH - *Nanoparticles/chemistry MH - Doxorubicin/pharmacology MH - Drug Delivery Systems MH - *Colorectal Neoplasms MH - Hydrogen-Ion Concentration OTO - NOTNLM OT - colorectal cancer OT - doxorubicin hydrochloride OT - nanobody OT - silk fibroin OT - silk fibroin nanoparticles EDAT- 2023/06/16 01:08 MHDA- 2023/06/26 06:41 CRDT- 2023/06/15 18:42 PHST- 2023/01/30 00:00 [received] PHST- 2023/06/15 00:00 [accepted] PHST- 2023/06/26 06:41 [medline] PHST- 2023/06/16 01:08 [pubmed] PHST- 2023/06/15 18:42 [entrez] AID - 10.1088/1748-605X/acdeba [doi] PST - epublish SO - Biomed Mater. 2023 Jun 23;18(4). doi: 10.1088/1748-605X/acdeba.