Improving payload capacity and anti-tumor efficacy of mesenchymal stem cells using tat peptide functionalized polymeric nanoparticles

Gopikrishna Moku, Buddhadev Layek, Lana Trautman, Samuel Putnam, Jayanth Panyam, Swayam Prabha

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 languageEnglish (US)
Article number491
JournalCancers
Volume11
Issue number4
DOIs
StatePublished - Apr 1 2019

Fingerprint

Mesenchymal Stromal Cells
Nanoparticles
Peptides
Trans-Activators
Neoplasms
Paclitaxel
Pharmaceutical Preparations
Polyglactin 910
Emulsions
Sulfhydryl Compounds
Lung Neoplasms
Neoplasm Metastasis
Growth

Keywords

  • Mesenchymal stem cells (MSCs)
  • Nano-engineered MSCs
  • Orthotopic lung tumor model
  • PLGA
  • Paclitaxel
  • TAT peptide

PubMed: MeSH publication types

  • Journal Article

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 journalArticle

@article{3234b2fcb4d04a82a2f2de85b38c8c43,
title = "Improving payload capacity and anti-tumor efficacy of mesenchymal stem cells using tat peptide functionalized polymeric nanoparticles",
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 = "Mesenchymal stem cells (MSCs), Nano-engineered MSCs, Orthotopic lung tumor model, PLGA, Paclitaxel, TAT peptide",
author = "Gopikrishna Moku and Buddhadev Layek and Lana Trautman and Samuel Putnam and Jayanth Panyam and Swayam Prabha",
year = "2019",
month = "4",
day = "1",
doi = "10.3390/cancers11040491",
language = "English (US)",
volume = "11",
journal = "Cancers",
issn = "2072-6694",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "4",

}

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

UR - http://www.scopus.com/inward/record.url?scp=85065317235&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065317235&partnerID=8YFLogxK

U2 - 10.3390/cancers11040491

DO - 10.3390/cancers11040491

M3 - Article

C2 - 30959908

AN - SCOPUS:85065317235

VL - 11

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 4

M1 - 491

ER -