Improving Payload Capacity and Anti-Tumor Efficacy of Mesenchymal Stem Cells Using TAT Peptide Functionalized Polymeric Nanoparticles
by
Gopikrishna Moku 1,†, Buddhadev Layek 2,†
, Lana Trautman 3, Samuel Putnam 3, Jayanth Panyam 1 and Swayam Prabha 1,2,*
Gopikrishna Moku 1,†, Buddhadev Layek 2,†, Lana Trautman 3, Samuel Putnam 3, Jayanth Panyam 1 and Swayam Prabha 1,2,*
1
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA
2
Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA
3
Breck School, 123 Ottawa Ave N, Golden Valley, MN 55422, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2019, 11(4), 491; https://doi.org/10.3390/cancers11040491
Received: 5 March 2019 / Revised: 27 March 2019 / Accepted: 2 April 2019 / Published: 6 April 2019
(This article belongs to the Special Issue Cancer Nanomedicine)
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.
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Keywords:
mesenchymal stem cells (MSCs); TAT peptide; PLGA; paclitaxel; nano-engineered MSCs; orthotopic lung tumor model
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MDPI and ACS Style
Moku, G.; Layek, B.; Trautman, L.; Putnam, S.; Panyam, J.; Prabha, S. Improving Payload Capacity and Anti-Tumor Efficacy of Mesenchymal Stem Cells Using TAT Peptide Functionalized Polymeric Nanoparticles. Cancers 2019, 11, 491.
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