PMID- 34179645
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210629
IS  - 2470-1343 (Electronic)
IS  - 2470-1343 (Linking)
VI  - 6
IP  - 24
DP  - 2021 Jun 22
TI  - Comparative Evaluation of Engineered Polypeptide Scaffolds in HER2-Targeting 
      Magnetic Nanocarrier Delivery.
PG  - 16000-16008
LID - 10.1021/acsomega.1c01811 [doi]
AB  - Targeted drug delivery is one of the most intriguing and challenging issues in 
      modern biomedicine. For active targeting, full-size IgG molecules (150 kDa) are 
      usually used. Recent studies have revealed that small artificial polypeptide 
      scaffolds such as DARPins (14 kDa) and affibodies (8 kDa) are much more promising 
      tools for drug delivery due to their small size, artificial nature, low 
      immunogenicity, and many other properties. However, there is no comparative 
      information on the targeting abilities of scaffold polypeptides, which should be 
      taken into account when developing drug delivery systems (DDSs). The present work 
      is the first comprehensive study on the comparison of the effectiveness of 
      different HER2-targeting proteins within the architecture of nanoparticles. 
      Namely, we synthesized trimodal nanoparticles: magnetic, fluorescent, and 
      directed toward HER2 oncomarker on cancer cells. The magnetic particles (MPs) 
      were covalently modified with (i) full-size IgG, 150 kDa, (ii) DARPin_G3, 14 kDa, 
      and (iii) affibody Z(HER2:342), 8 kDa. We showed that the number of DARPin_G3 and 
      affibody Z(HER2:342) molecules conjugated to the nanoparticle surface are 10 and 
      40 times higher, respectively, than the corresponding value for trastuzumab. 
      Using the methods of magnetic particle quantification (MPQ)-cytometry and 
      confocal microscopy, we showed that all types of the obtained magnetic conjugates 
      specifically labeled HER2-overexpressing cells. Namely, we demonstrated that 
      particle binding to HER2-positive cells is 1113 +/- 39 fg/cell for MP*trastuzumab, 
      1431 +/- 186 fg/cell for MP*Z(HER2:342), and 625+/-21 fg/cell for MP*DARPin_G3, which 
      are 2.77, 2.75, and 2.30 times higher than the corresponding values for control 
      HER2-negative cells. Thus, we showed that the smallest HER2-recognizing 
      polypeptide affibody Z(HER2:342) is more effective in terms of specificity and 
      selectivity in nanoparticle-mediated cell labeling.
CI  - (c) 2021 The Authors. Published by American Chemical Society.
FAU - Shipunova, Victoria O
AU  - Shipunova VO
AUID- ORCID: 0000-0001-6361-1042
AD  - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of 
      Sciences, 16/10 Miklukho-Maklaya Street, Moscow 117997, Russia.
AD  - Moscow Institute of Physics and Technology, 9 Institutskiy per., Dolgoprudny 
      141701, Russia.
AD  - MEPhI (Moscow Engineering Physics Institute), Institute of Engineering Physics 
      for Biomedicine (PhysBio), 31 Kashirskoe Shosse, Moscow 115409, Russia.
AD  - Sirius University of Science and Technology, 1 Olympic Avenue, Sochi 354340, 
      Russia.
FAU - Kolesnikova, Olga A
AU  - Kolesnikova OA
AD  - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of 
      Sciences, 16/10 Miklukho-Maklaya Street, Moscow 117997, Russia.
FAU - Kotelnikova, Polina A
AU  - Kotelnikova PA
AD  - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of 
      Sciences, 16/10 Miklukho-Maklaya Street, Moscow 117997, Russia.
FAU - Soloviev, Vladislav D
AU  - Soloviev VD
AD  - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of 
      Sciences, 16/10 Miklukho-Maklaya Street, Moscow 117997, Russia.
AD  - Sirius University of Science and Technology, 1 Olympic Avenue, Sochi 354340, 
      Russia.
FAU - Popov, Anton A
AU  - Popov AA
AD  - MEPhI (Moscow Engineering Physics Institute), Institute of Engineering Physics 
      for Biomedicine (PhysBio), 31 Kashirskoe Shosse, Moscow 115409, Russia.
FAU - Proshkina, Galina M
AU  - Proshkina GM
AD  - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of 
      Sciences, 16/10 Miklukho-Maklaya Street, Moscow 117997, Russia.
FAU - Nikitin, Maxim P
AU  - Nikitin MP
AD  - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of 
      Sciences, 16/10 Miklukho-Maklaya Street, Moscow 117997, Russia.
AD  - Moscow Institute of Physics and Technology, 9 Institutskiy per., Dolgoprudny 
      141701, Russia.
AD  - Sirius University of Science and Technology, 1 Olympic Avenue, Sochi 354340, 
      Russia.
FAU - Deyev, Sergey M
AU  - Deyev SM
AD  - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of 
      Sciences, 16/10 Miklukho-Maklaya Street, Moscow 117997, Russia.
AD  - MEPhI (Moscow Engineering Physics Institute), Institute of Engineering Physics 
      for Biomedicine (PhysBio), 31 Kashirskoe Shosse, Moscow 115409, Russia.
LA  - eng
PT  - Journal Article
DEP - 20210610
PL  - United States
TA  - ACS Omega
JT  - ACS omega
JID - 101691658
PMC - PMC8223436
COIS- The authors declare no competing financial interest.
EDAT- 2021/06/29 06:00
MHDA- 2021/06/29 06:01
PMCR- 2021/06/10
CRDT- 2021/06/28 06:11
PHST- 2021/04/05 00:00 [received]
PHST- 2021/05/31 00:00 [accepted]
PHST- 2021/06/28 06:11 [entrez]
PHST- 2021/06/29 06:00 [pubmed]
PHST- 2021/06/29 06:01 [medline]
PHST- 2021/06/10 00:00 [pmc-release]
AID - 10.1021/acsomega.1c01811 [doi]
PST - epublish
SO  - ACS Omega. 2021 Jun 10;6(24):16000-16008. doi: 10.1021/acsomega.1c01811. 
      eCollection 2021 Jun 22.