Transformable Nanomaterials as an Artificial Extracellular Matrix for Inhibiting Tumor Invasion and Metastasis.
Tumor metastasis is one of the big challenges in cancer treatment and is often associated with high patient mortality. Until now, there is an agreement that tumor invasion and metastasis are related to degradation of extracellular matrix (ECM) by enzymes. Inspired by the formation of natural ECM and the in situ self-assembly strategy developed in our group, herein, we in situ constructed an artificial extracellular matrix (AECM) based on transformable Laminin (LN)-mimic peptide 1 (BP-KLVFFK-GGDGR-YIGSR) for inhibition of tumor invasion and metastasis. The peptide 1 was composed of three modules including (i) the hydrophobic bis-pyrene (BP) unit for forming and tracing nanoparticles; (ii) the KLVFF peptide motif that was inclined to form and stabilize fibrous structures through intermolecular hydrogen bonds; and (iii) the Y-type RGD-YIGSR motif, derived from LN conserved sequence, served as ligands to bind cancer cell surfaces. The peptide 1 formed nanoparticles (1-NPs) by the rapid precipitation method, owing to strong hydrophobic interactions of BP. Upon intravenous injection, 1-NPs effectively accumulated in the tumor site due to the enhanced permeability and retention (EPR) effect and/or targeting capability of RGD-YIGSR. The accumulated 1-NPs simultaneously transformed into nanofibers (1-NFs) around the solid tumor and further entwined to form AECM upon binding to receptors on the tumor cell surfaces. The AECM stably existed in the primary tumor site over 72 h, which consequently resulted in efficiently inhibiting the lung metastasis in breast and melanoma tumor models. The inhibition rates in two tumor models were 82.3% and 50.0%, respectively. This in vivo self-assembly strategy could be widely utilized to design effective drug-free biomaterials for inhibiting the tumor invasion and metastasis.
National Engineering Research Center of Industrial Crystallization Technology, State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, P. R. China.|CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
Xiao-Xue
XX
Hu
CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
Ping-Ping
PP
He
CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
Guo-Bin
GB
Qi
CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
Yu-Juan
YJ
Gao
CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
Yao-Xin
YX
Lin
CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
Chao
C
Yang
CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
Pei-Pei
PP
Yang
National Engineering Research Center of Industrial Crystallization Technology, State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, P. R. China.
Hongxun
0000-0001-6445-7737
H
Hao
CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
Lei
L
Wang
CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
Hao
0000-0002-1961-0787
H
Wang
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D005109:Extracellular Matrix / Q000737:chemistry*; D006801:Humans; D007797:Laminin / Q000737:chemistry; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D051379:Mice; D018716:Molecular Mimicry; D057139:Nanofibers / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010316:Particle Size; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry; D010539:Permeability; D011721:Pyrenes / Q000737:chemistry
D000970:Antineoplastic Agents; D007797:Laminin; D010455:Peptides; D011721:Pyrenes
metastasis; peptide; self-assembly; therapy; tumor