4.8 Article

One-step and facile synthesis of peptide-like poly(melphalan) nanodrug for cancer therapy

Journal

NANO TODAY
Volume 37, Issue -, Pages -

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.nantod.2021.101098

Keywords

Polyprodrug; Melphalan; Peptide; Self-delivery; Cancer therapy

Funding

  1. National Science and Technology Major Project of the Ministry of Science and Technology of China [2018ZX10301402]
  2. Natural Science Foundation for Young Scientists of Shanxi Province, China [201901D211473]
  3. Guangdong Innovative and Entrepreneurial Research Team Program [2016ZT06S029]
  4. National Natural Science Foundation of China [51973243]
  5. International Cooperation and Exchange of the National Natural Science Foundation of China [51820105004]
  6. Basic and Applied Basic Research Foundation of Guangdong [2019A1515110903]
  7. Research Start-up Fund of Post-doctoral, of SAHSYSU [ZSQYRSFPD0016]
  8. Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi, China [2019L0660]
  9. Outstanding Doctor Funding Award of Shanxi Province, China [SXYBKY2018001]
  10. Doctoral Scientific Research Foundation of Changzhi Medical College, China [BS201909]

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The study developed a peptide-like polydrug for cancer chemotherapy using a simple one-step synthesis strategy, showing high drug loading and stability, and good therapeutic effects on tumors in vivo.
The clinical applications of polymer-based nanomedicines have been restricted by their complicated synthesis processes, biosafety issues, and uncontrollable drug loading. In this study, we developed a peptide-like polydrug for cancer chemotherapy using the FDA-approved drug melphalan via a simple one-step synthesis strategy. The prepared poly (melphalan) (PMP)-PEG was characterized through standard methods and formulated into sub-100 nm nanoparticles using the nanoprecipitation method. The poly (melphalan)-PEG nanoparticles (PMP NPs) showed controllable drug loading (up to 70 wt%) with high stability in buffers. In vitro cell viability studies showed good cell uptake behavior and high cytotoxicity of the PMP-NPs compared to Evomela controls (a commercial and clinical melphalan formulation). For in vivo mouse models tests, the PMP-NPs could accumulate in the tumor sites for >= 1 week and effectively inhibited tumor growth with minimal side-effects. This peptide synthesis strategy and a melphalan based pol ydrug nanoplatform may be promising for new drug development and effective cancer therapy. (C) 2021 Elsevier Ltd. All rights reserved.

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