Simultaneous targeting of primary tumor, draining lymph node, and distant metastases through high endothelial venule-targeted delivery.
Journal
Nano today
ISSN: 1748-0132
Titre abrégé: Nano Today
Pays: England
ID NLM: 101297352
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
entrez:
4
1
2021
pubmed:
5
1
2021
medline:
5
1
2021
Statut:
ppublish
Résumé
Cancer patients with malignant involvement of tumor-draining lymph nodes (TDLNs) and distant metastases have the poorest prognosis. A drug delivery platform that targets the primary tumor, TDLNs, and metastatic niches simultaneously, remains to be developed. Here, we generated a novel monoclonal antibody (MHA112) against peripheral node addressin (PNAd), a family of glycoproteins expressed on high endothelial venules (HEVs), which are present constitutively in the lymph nodes (LNs) and formed ectopically in the tumor stroma. MHA112 was endocytosed by PNAd-expressing cells, where it passed through the lysosomes. MHA112 conjugated antineoplastic drug Paclitaxel (Taxol) (MHA112-Taxol) delivered Taxol effectively to the HEV-containing tumors, TDLNs, and metastatic lesions. MHA112-Taxol treatment significantly reduced primary tumor size as well as metastatic lesions in a number of mouse and human tumor xenografts tested. These data, for the first time, indicate that human metastatic lesions contain HEVs and provide a platform that permits simultaneous targeted delivery of antineoplastic drugs to the three key sites of primary tumor, TDLNs, and metastases.
Identifiants
pubmed: 33391389
doi: 10.1016/j.nantod.2020.101045
pmc: PMC7774643
mid: NIHMS1653568
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : NIAID NIH HHS
ID : P01 AI153003
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI114496
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL145813
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI062765
Pays : United States
Déclaration de conflit d'intérêts
Competing interests: All authors declare that they have no competing interests. R.A holds equity in NanoTomer, Inc. a biotech company that has licensed certain patent applications from Mass General Brigham generated by R.A. Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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