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Antibody-Assisted Delivery of a Peptide–Drug Conjugate for Targeted Cancer Therapy
- Source :
- Molecular Pharmaceutics. 16:165-172
- Publication Year :
- 2018
- Publisher :
- American Chemical Society (ACS), 2018.
-
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 (Abcot) 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-APTEDB), yielding the model PDC, cot-APTEDB-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 Abcot in situ, designated HC[cot-APTEDB-SN38/Abcot]. In glioblastoma-bearing mice, in situ HC[cot-APTEDB-SN38/Abcot] significantly extended the circulation half-life of cot-APTEDB-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.
- Subjects :
- Immunoconjugates
Cancer therapy
Mice, Nude
Pharmaceutical Science
Antineoplastic Agents
02 engineering and technology
Irinotecan
030226 pharmacology & pharmacy
Antibodies
Mice
03 medical and health sciences
Drug Delivery Systems
0302 clinical medicine
In vivo
Cell Line, Tumor
Drug Discovery
In Situ Nick-End Labeling
Animals
Humans
Cytotoxicity
Peptide drug conjugates
Mice, Inbred BALB C
biology
Chemistry
Assisted delivery
hemic and immune systems
Glioma
021001 nanoscience & nanotechnology
Fibronectin
biology.protein
Cancer research
Molecular Medicine
Female
Antibody
Peptides
0210 nano-technology
Conjugate
Subjects
Details
- ISSN :
- 15438392 and 15438384
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- Molecular Pharmaceutics
- Accession number :
- edsair.doi.dedup.....c7b1e8e498efb7537e33be1530bd9b7b