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Antibody-Assisted Delivery of a Peptide-Drug Conjugate for Targeted Cancer Therapy

Title
Antibody-Assisted Delivery of a Peptide-Drug Conjugate for Targeted Cancer Therapy
Authors
Kim, HyungjunHwang, DobeenChoi, MinsukLee, SoyoungKang, SukmoLee, YonghyunKim, SunghyunChung, JunhoJon, Sangyong
Ewha Authors
이용현
Issue Date
2019
Journal Title
MOLECULAR PHARMACEUTICS
ISSN
1543-8384JCR Link
Citation
MOLECULAR PHARMACEUTICS vol. 16, no. 1, pp. 165 - 172
Keywords
aptidesanticotinine antibodycancer therapyextra domain B of fibronectinpeptide-drug conjugatesSN38
Publisher
AMER CHEMICAL SOC
Indexed
SCIE; SCOPUS WOS
Document Type
Article
Abstract
A number of cancer-targeting peptide-drug conjugates (PDCs) have been explored as alternatives to antibody drug conjugates (ADCs) for targeted cancer therapy. However, the much shorter circulation half-life of PDCs compared with ADCs in vivo has limited their therapeutic value and thus their translation into the clinic, highlighting the need to develop new approaches for extending the half-life of PDCs. Here, we report a new strategy for targeted cancer therapy of a PDC based on a molecular hybrid between an antihapten antibody and a hapten-labeled PDC. An anticotinine antibody (Ab(cot)) was used as a model antihapten antibody. The anticancer drug SN38 was linked to a cotinine-labeled aptide specific to extra domain B of fibronectin (cot-APT(EDB)), yielding the model PDC, cot-APT(EDB)-SN38. The cotinine-labeled PDC showed specific binding to and cytotoxicity toward an EDB-overexpressing human glioblastoma cell line (U87MG) and also formed a hybrid complex (HC) with Ab(cot) in situ, designated HC[cot-APT(EDB)-SN38/Ab(cot)]. In glioblastoma-bearing mice, in situ HC[cot-APT(EDB)-SN38/Ab(cot)] significantly extended the circulation half-life of cot-APT(EDB)-SN38 in blood, and it enhanced accumulation and penetration within the tumor and, ultimately, inhibition of tumor growth. These findings suggest that the present platform holds promise as a new, targeted delivery strategy for PDCs in anticancer therapy.
DOI
10.1021/acs.molpharmaceut.8b00924
Appears in Collections:
약학대학 > 약학과 > Journal papers
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