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Computer-Aided Design of Lasso-like Self-Assembling Anticancer Peptides with Multiple Functions for Targeted Self-Delivery and Cancer Treatments.
Pei, Pengfei; Chen, Long; Fan, Ruru; Zhou, Xi-Rui; Feng, Shan; Liu, Hangrui; Guo, Quanqiang; Yin, Huiwei; Zhang, Qiang; Sun, Fude; Peng, Liang; Wei, Peng; He, Chengzhi; Qiao, Renzhong; Wang, Zai; Luo, Shi-Zhong.
Afiliación
  • Pei P; Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, P.R. China.
  • Chen L; Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, P.R. China.
  • Fan R; Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, P.R. China.
  • Zhou XR; Division of Metrology in Chemistry, National Institute of Metrology, Beijing 100029, P.R. China.
  • Feng S; School of Life Sciences, Tsinghua University, Beijing 100084, P.R. China.
  • Liu H; Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, P.R. China.
  • Guo Q; Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, P.R. China.
  • Yin H; Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, P.R. China.
  • Zhang Q; Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, P.R. China.
  • Sun F; Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, P.R. China.
  • Peng L; Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, P.R. China.
  • Wei P; School of Traditional Chinese Medicine, School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, P.R. China.
  • He C; Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, P.R. China.
  • Qiao R; Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, P.R. China.
  • Wang Z; Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, P.R. China.
  • Luo SZ; Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, P.R. China.
ACS Nano ; 16(9): 13783-13799, 2022 09 27.
Article en En | MEDLINE | ID: mdl-36099446
Anticancer peptides are promising drug candidates for cancer treatment, but the short circulation time and low delivery efficiency limit their clinical applications. Herein, we designed several lasso-like self-assembling anticancer peptides (LASAPs) integrated with multiple functions by a computer-aided approach. Among these LASAPs, LASAP1 (CRGDKGPDCGKAFRRFLGALFKALSHLL, 1-9 disulfide bond) was determined to be superior to the others because it can self-assemble into homogeneous nanoparticles and exhibits improved stability in serum. Thus, LASAP1 was chosen for proving the design idea. LASAP1 can self-assemble into nanoparticles displaying iRGD on the surface because of its amphiphilic structure and accumulate to the tumor site after injection because of the EPR effect and iRGD targeting to αVß3 integrin. The nanoparticles could disassemble in the acidic microenvironment of the solid tumor, and cleaved by the overexpressed hK2, which was secreted by prostate tumor cells, to release the effector peptide PTP-7b (FLGALFKALSHLL), which was further activated by the acidic pH. Therefore, LASAP1 could target the orthotopic prostate tumor in the model mice after intraperitoneal injection and specifically inhibit tumor growth, with low systematic toxicity. Combining the multiple targeting functions, LASAP1 represents a promising design of self-delivery of peptide drugs for targeted cancer treatments.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Nanopartículas / Antineoplásicos Límite: Animals / Humans / Male Idioma: En Revista: ACS Nano Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Nanopartículas / Antineoplásicos Límite: Animals / Humans / Male Idioma: En Revista: ACS Nano Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos