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.
| Original language | English (US) |
|---|---|
| Article number | 491 |
| Journal | Cancers |
| Volume | 11 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2019 |
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Keywords
- Mesenchymal stem cells (MSCs)
- Nano-engineered MSCs
- Orthotopic lung tumor model
- PLGA
- Paclitaxel
- TAT peptide
Cite this
Improving payload capacity and anti-tumor efficacy of mesenchymal stem cells using tat peptide functionalized polymeric nanoparticles. / Moku, Gopikrishna; Layek, Buddhadev; Trautman, Lana; Putnam, Samuel; Panyam, Jayanth; Prabha, Swayam.
In: Cancers, Vol. 11, No. 4, 491, 01.04.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Improving payload capacity and anti-tumor efficacy of mesenchymal stem cells using tat peptide functionalized polymeric nanoparticles
AU - Moku, Gopikrishna
AU - Layek, Buddhadev
AU - Trautman, Lana
AU - Putnam, Samuel
AU - Panyam, Jayanth
AU - Prabha, Swayam
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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.
AB - 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.
KW - Mesenchymal stem cells (MSCs)
KW - Nano-engineered MSCs
KW - Orthotopic lung tumor model
KW - PLGA
KW - Paclitaxel
KW - TAT peptide
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UR - http://www.scopus.com/inward/citedby.url?scp=85065317235&partnerID=8YFLogxK
U2 - 10.3390/cancers11040491
DO - 10.3390/cancers11040491
M3 - Article
VL - 11
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 4
M1 - 491
ER -