title: A tenascin C targeted nanoliposome with navitoclax for specifically eradicating of cancer-associated fibroblasts.
abstract: Cancer-associated fibroblasts (CAFs) play a vitally important role during tumor progression. Navitoclax (Nav) can specifically induce apoptosis in CAFs. The present study aims to develop a novel CAF-targeted nanoliposome for cancer therapy. Nav-loaded nanoliposomes modified with peptide FH (FH-SSL-Nav), which specifically binds to tenascin C, a protein mainly expressed by CAFs, were formulated and characterized. Several experiments were performed to evaluate CAFs selective apoptosis, targeting and eradicating. Compared with SSL-Nav, FH-SSL-Nav achieved higher cellular uptake, and exhibited stronger cytotoxicity in vitro. The in vivo tumor stroma targeting effect was further confirmed by near infrared imaging. Accordingly, FH-SSL-Nav displayed improved tumor growth inhibition by eradicating CAFs in Hep G2 tumor-bearing nude mice model. In conclusion, FH-SSL-Nav could achieve targeting delivery of Nav to CAFs in vitro and in vivo, and may offer a potential strategy for cancer therapy based on tumor stroma. From the Clinical Editor: The progression of cancer cells often depends on the underlying tumor microenvironment, in which cancer-associated fibroblasts play an important role. In this article, the authors developed targeted therapy against CAFs using liposomes as carriers. This new modality was shown to be more effective in tumor killing both in vitro and in vivo. The finding may open a new era in cancer therapy.
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, China; State Key Laboratory of Natural and Biomimetic Drugs, Beijing, China.
authors.forename: Binlong
authors.initials: B
authors.lastname: Chen
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, China; State Key Laboratory of Natural and Biomimetic Drugs, Beijing, China.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, China; State Key Laboratory of Natural and Biomimetic Drugs, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, China; State Key Laboratory of Natural and Biomimetic Drugs, Beijing, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Song
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, China; State Key Laboratory of Natural and Biomimetic Drugs, Beijing, China.
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, China. Electronic address: pawpaw009@126.com.
authors.forename: Wenbing
authors.initials: W
authors.lastname: Dai
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, China; State Key Laboratory of Natural and Biomimetic Drugs, Beijing, China. Electronic address: zqdodo@bjmu.edu.cn.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000814:Aniline Compounds / Q000008:administration & dosage*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058990:Molecular Targeted Therapy / Q000379:methods; D053769:Nanocapsules / Q000737:chemistry*; D009369:Neoplasms; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology*; D010455:Peptides / Q000493:pharmacokinetics*; D013449:Sulfonamides / Q000008:administration & dosage*; D019063:Tenascin / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D008081:Liposomes; D053769:Nanocapsules; D010455:Peptides; D013449:Sulfonamides; D019063:Tenascin; C528561:navitoclax
keywords: Cancer-associated fibroblasts; Nanoliposome; Navitoclax; Target delivery; Tenascin C; Tumor microenvironment