A multi-functional polymeric carrier for simultaneous positron emission tomography imaging and combination therapy

Jingjing Sun, Lingyi Sun, Jianchun Li, Jieni Xu, Zhuoya Wan, Zubin Ouyang, Lei Liang, Song Li, Dexing Zeng

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Multifunctional nanoplatforms offering simultaneous imaging and therapeutic functions have been recognized as a highly promising strategy for personalized nanomedicine. In this work, we synthesized a farnesylthiosalicylate (FTS, a nontoxic Ras antagonist) based triblock copolymer POEG-b-PVBA-b-PFTS (POVF) composed of a poly(oligo(ethylene glycol) methacrylate) (POEG) hydrophilic block, a poly(FTS) hydrophobic block, and a poly(4-vinylbenzyl azide) (PVBA) middle block. The POVF polymer itself was active in inhibiting the tumor growth in vitro and in vivo. Besides, it could serve as a carrier to effectively encapsulate paclitaxel (PTX) to form stable PTX/POVF mixed micelles with a diameter around 100 nm. Meanwhile, POVF polymer provides the active azide group for incorporating a positron emission tomography (PET) imaging modality via a facile strategy based on metal-free click chemistry. This nanocarrier system could not only be used for co-delivery of PTX and FTS, but also for PET imaging guided drug delivery. In the 4T1.2 tumor bearing mice, PET imaging showed rapid uptake and slow clearance of radiolabeled PTX/POVF nanomicelles in the tumor tissues. In addition, the FTS-based multi-functional nanocarrier was able to inhibit tumor growth effectively, and the co-delivery of PTX by the carrier further improved the therapeutic effect. Statement of Significance: Due to the intrinsic heterogeneity of cancer and variability in individual patient response, personalized nanomedicine based on multi-functional carriers that integrate the functionalities of combination therapy and imaging guidance is highly demanded. Here we developed a multi-functional nanocarrier based on triblock copolymer POEG-b-PVBA-b-PFTS (POVF), which could not only be used for co-delivery of anticancer drugs PTX and Ras inhibitor FTS, but also for PET imaging guided drug delivery. The POVF carrier itself was active in inhibiting the tumor growth in vitro and in vivo. Besides, it was effective in formulating PTX with high drug loading capacity, which further enhanced the tumor inhibition effect. Meanwhile, we developed a simple and universal approach to incorporate a PET radioisotope (Zr-89 and Cu-64) into the azide-containing PTX/POVF micelles via metal-free click chemistry in aqueous solution. The radiolabeled PTX/POVF micelles exhibited excellent serum stability, rapid tumor uptake and slow clearance, which validated the feasibility of the PET image-guided delivery of PTX/POVF micelles.

Original languageEnglish (US)
Pages (from-to)312-322
Number of pages11
JournalActa Biomaterialia
Volume75
DOIs
StatePublished - Jul 15 2018
Externally publishedYes

Fingerprint

Positron emission tomography
Paclitaxel
Positron-Emission Tomography
Tumors
Imaging techniques
Azides
Micelles
Medical nanotechnology
Neoplasms
Click Chemistry
Drug delivery
Nanomedicine
Therapeutics
Block copolymers
Bearings (structural)
Pharmaceutical Preparations
Polymers
Growth
Metals
Radioisotopes

Keywords

  • Drug delivery
  • Farnesyl thiosalicylic acid (FTS)
  • Paclitaxel
  • PET imaging
  • Prodrug micelles

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

Cite this

A multi-functional polymeric carrier for simultaneous positron emission tomography imaging and combination therapy. / Sun, Jingjing; Sun, Lingyi; Li, Jianchun; Xu, Jieni; Wan, Zhuoya; Ouyang, Zubin; Liang, Lei; Li, Song; Zeng, Dexing.

In: Acta Biomaterialia, Vol. 75, 15.07.2018, p. 312-322.

Research output: Contribution to journalArticle

Sun, Jingjing ; Sun, Lingyi ; Li, Jianchun ; Xu, Jieni ; Wan, Zhuoya ; Ouyang, Zubin ; Liang, Lei ; Li, Song ; Zeng, Dexing. / A multi-functional polymeric carrier for simultaneous positron emission tomography imaging and combination therapy. In: Acta Biomaterialia. 2018 ; Vol. 75. pp. 312-322.
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T1 - A multi-functional polymeric carrier for simultaneous positron emission tomography imaging and combination therapy

AU - Sun, Jingjing

AU - Sun, Lingyi

AU - Li, Jianchun

AU - Xu, Jieni

AU - Wan, Zhuoya

AU - Ouyang, Zubin

AU - Liang, Lei

AU - Li, Song

AU - Zeng, Dexing

PY - 2018/7/15

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N2 - Multifunctional nanoplatforms offering simultaneous imaging and therapeutic functions have been recognized as a highly promising strategy for personalized nanomedicine. In this work, we synthesized a farnesylthiosalicylate (FTS, a nontoxic Ras antagonist) based triblock copolymer POEG-b-PVBA-b-PFTS (POVF) composed of a poly(oligo(ethylene glycol) methacrylate) (POEG) hydrophilic block, a poly(FTS) hydrophobic block, and a poly(4-vinylbenzyl azide) (PVBA) middle block. The POVF polymer itself was active in inhibiting the tumor growth in vitro and in vivo. Besides, it could serve as a carrier to effectively encapsulate paclitaxel (PTX) to form stable PTX/POVF mixed micelles with a diameter around 100 nm. Meanwhile, POVF polymer provides the active azide group for incorporating a positron emission tomography (PET) imaging modality via a facile strategy based on metal-free click chemistry. This nanocarrier system could not only be used for co-delivery of PTX and FTS, but also for PET imaging guided drug delivery. In the 4T1.2 tumor bearing mice, PET imaging showed rapid uptake and slow clearance of radiolabeled PTX/POVF nanomicelles in the tumor tissues. In addition, the FTS-based multi-functional nanocarrier was able to inhibit tumor growth effectively, and the co-delivery of PTX by the carrier further improved the therapeutic effect. Statement of Significance: Due to the intrinsic heterogeneity of cancer and variability in individual patient response, personalized nanomedicine based on multi-functional carriers that integrate the functionalities of combination therapy and imaging guidance is highly demanded. Here we developed a multi-functional nanocarrier based on triblock copolymer POEG-b-PVBA-b-PFTS (POVF), which could not only be used for co-delivery of anticancer drugs PTX and Ras inhibitor FTS, but also for PET imaging guided drug delivery. The POVF carrier itself was active in inhibiting the tumor growth in vitro and in vivo. Besides, it was effective in formulating PTX with high drug loading capacity, which further enhanced the tumor inhibition effect. Meanwhile, we developed a simple and universal approach to incorporate a PET radioisotope (Zr-89 and Cu-64) into the azide-containing PTX/POVF micelles via metal-free click chemistry in aqueous solution. The radiolabeled PTX/POVF micelles exhibited excellent serum stability, rapid tumor uptake and slow clearance, which validated the feasibility of the PET image-guided delivery of PTX/POVF micelles.

AB - Multifunctional nanoplatforms offering simultaneous imaging and therapeutic functions have been recognized as a highly promising strategy for personalized nanomedicine. In this work, we synthesized a farnesylthiosalicylate (FTS, a nontoxic Ras antagonist) based triblock copolymer POEG-b-PVBA-b-PFTS (POVF) composed of a poly(oligo(ethylene glycol) methacrylate) (POEG) hydrophilic block, a poly(FTS) hydrophobic block, and a poly(4-vinylbenzyl azide) (PVBA) middle block. The POVF polymer itself was active in inhibiting the tumor growth in vitro and in vivo. Besides, it could serve as a carrier to effectively encapsulate paclitaxel (PTX) to form stable PTX/POVF mixed micelles with a diameter around 100 nm. Meanwhile, POVF polymer provides the active azide group for incorporating a positron emission tomography (PET) imaging modality via a facile strategy based on metal-free click chemistry. This nanocarrier system could not only be used for co-delivery of PTX and FTS, but also for PET imaging guided drug delivery. In the 4T1.2 tumor bearing mice, PET imaging showed rapid uptake and slow clearance of radiolabeled PTX/POVF nanomicelles in the tumor tissues. In addition, the FTS-based multi-functional nanocarrier was able to inhibit tumor growth effectively, and the co-delivery of PTX by the carrier further improved the therapeutic effect. Statement of Significance: Due to the intrinsic heterogeneity of cancer and variability in individual patient response, personalized nanomedicine based on multi-functional carriers that integrate the functionalities of combination therapy and imaging guidance is highly demanded. Here we developed a multi-functional nanocarrier based on triblock copolymer POEG-b-PVBA-b-PFTS (POVF), which could not only be used for co-delivery of anticancer drugs PTX and Ras inhibitor FTS, but also for PET imaging guided drug delivery. The POVF carrier itself was active in inhibiting the tumor growth in vitro and in vivo. Besides, it was effective in formulating PTX with high drug loading capacity, which further enhanced the tumor inhibition effect. Meanwhile, we developed a simple and universal approach to incorporate a PET radioisotope (Zr-89 and Cu-64) into the azide-containing PTX/POVF micelles via metal-free click chemistry in aqueous solution. The radiolabeled PTX/POVF micelles exhibited excellent serum stability, rapid tumor uptake and slow clearance, which validated the feasibility of the PET image-guided delivery of PTX/POVF micelles.

KW - Drug delivery

KW - Farnesyl thiosalicylic acid (FTS)

KW - Paclitaxel

KW - PET imaging

KW - Prodrug micelles

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