2. Academic Validation
  3. Improving Payload Capacity and Anti-Tumor Efficacy of Mesenchymal Stem Cells Using TAT Peptide Functionalized Polymeric Nanoparticles

Improving Payload Capacity and Anti-Tumor Efficacy of Mesenchymal Stem Cells Using TAT Peptide Functionalized Polymeric Nanoparticles

  • Cancers (Basel). 2019 Apr 6;11(4):491. doi: 10.3390/cancers11040491.
Gopikrishna Moku 1,  Buddhadev Layek 2,  Lana Trautman 3,  Samuel Putnam 4,  Jayanth Panyam 5,  Swayam Prabha 6 7
Affiliations

Affiliations

  • 1 Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA. gopikrishna.moku@gmail.com.
  • 2 Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA. blayek@umn.edu.
  • 3 Breck School, 123 Ottawa Ave N, Golden Valley, MN 55422, USA. traula@student.breckschool.org.
  • 4 Breck School, 123 Ottawa Ave N, Golden Valley, MN 55422, USA. putnsa@student.breckschool.org.
  • 5 Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA. jpanyam@umn.edu.
  • 6 Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA. prabh025@umn.edu.
  • 7 Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA. prabh025@umn.edu.
PMID: 30959908 DOI: 10.3390/cancers11040491
Abstract

Mesenchymal stem cells (MSCs) accumulate specifically in both primary tumors and metastases following systemic administration. However, the poor payload capacity of MSCs limits their use in small molecule drug delivery. To improve drug payload in MSCs, we explored polymeric nanoparticles that were functionalized with transactivator of transcription (TAT) peptide. Paclitaxel loaded poly(DL-lactide-co-glycolide) (PLGA) nanoparticles (15⁻16% w/w paclitaxel; diameter of 225 ± 7 nm; and zeta potential of -15 ± 4 mV) were fabricated by emulsion-solvent evaporation method, followed by TAT-conjugation to the surface of nanoparticles via maleimide-thiol chemistry. Our studies demonstrated that TAT functionalization improved the intracellular accumulation and retention of nanoparticles in MSCs. Further, nano-engineering of MSCs did not alter the migration and differentiation potential of MSCs. Treatment with nano-engineered MSCs resulted in significant (p < 0.05) inhibition of tumor growth and improved survival (p < 0.0001) in a mouse orthotopic model of lung Cancer compared to that with free or nanoparticle encapsulated drug. In summary, our results demonstrated that MSCs engineered using TAT functionalized nanoparticles serve as an efficient carrier for tumor specific delivery of Anticancer drugs, resulting in greatly improved therapeutic efficacy.

Keywords

PLGA; TAT peptide; mesenchymal stem cells (MSCs); nano-engineered MSCs; orthotopic lung tumor model; paclitaxel.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z