Dual Regioselective Targeting the Same Receptor in Nanoparticle-Mediated Combination Immuno/Chemotherapy for Enhanced Image-Guided Cancer Treatment - laboratoire Lasers, Plasmas et Procédés Photoniques Accéder directement au contenu
Article Dans Une Revue ACS Nano Année : 2020

Dual Regioselective Targeting the Same Receptor in Nanoparticle-Mediated Combination Immuno/Chemotherapy for Enhanced Image-Guided Cancer Treatment

Victoria O Shipunova
  • Fonction : Auteur
Elena N Komedchikova
  • Fonction : Auteur
Polina A Kotelnikova
  • Fonction : Auteur
Ivan V Zelepukin
  • Fonction : Auteur
Alexey A Schulga
  • Fonction : Auteur
Galina M Proshkina
  • Fonction : Auteur
Elena I Shramova
  • Fonction : Auteur
Hilliard L Kutscher
  • Fonction : Auteur
Georgij B Telegin
  • Fonction : Auteur
Paras N Prasad
  • Fonction : Auteur
Sergey M Deyev
  • Fonction : Auteur

Résumé

When combined with immunotherapy, image-guided targeted delivery of chemotherapeutic agents is a promising direction for combination cancer theranostics, but this approach has so far produced only limited success due to a lack of molecular targets on the cell surface and low therapeutic index of conventional chemotherapy drugs. Here, we demonstrate a synergistic strategy of combination immuno/chemotherapy in conditions of dual regioselective targeting, implying vectoring of two distinct binding sites of a single oncomarker (here, HER2) with theranostic compounds having a different mechanism of action. We use: (i) PLGA nanoformulation, loaded with an imaging diagnostic fluorescent dye (Nile Red) and a chemotherapeutic drug (doxorubicin), and functionalized with affibody ZHER2:342 (8 kDa); (ii) bifunctional genetically engineered DARP-LoPE (42 kDa) immunotoxin comprising of a low-immunogenic modification of therapeutic Pseudomonas exotoxin A (LoPE) and a scaffold targeting protein, DARPin9.29 (14 kDa). According to the proposed strategy, the first chemotherapeutic nanoagent is targeted by the affibody to subdomain III and IV of HER2 with 60-fold specificity compared with non-targeted particles, while the second immunotoxin is effectively targeted by DARPin molecule to subdomain I of HER2. We demonstrate that this dual targeting strategy can enhance anticancer therapy of HER2-positive cells with a very strong synergy, which made possible 1000-fold decrease of
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Dates et versions

hal-03163227 , version 1 (09-03-2021)

Identifiants

Citer

Victoria O Shipunova, Elena N Komedchikova, Polina A Kotelnikova, Ivan V Zelepukin, Alexey A Schulga, et al.. Dual Regioselective Targeting the Same Receptor in Nanoparticle-Mediated Combination Immuno/Chemotherapy for Enhanced Image-Guided Cancer Treatment. ACS Nano, 2020, 14 (10), pp.12781-12795. ⟨10.1021/acsnano.0c03421⟩. ⟨hal-03163227⟩

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