Self-Assembled Disulfide Bond Bearing Paclitaxel—Camptothecin Prodrug Nanoparticle for Lung Cancer Therapy

Jingyan Gao, Xiaodong Ma, Lirong Zhang, Jiaqi Yan, Huaguang Cui, Yuezhou Zhang, Dongqing Wang, Hongbo Zhang

Tutkimustuotos: LehtiartikkeliArtikkeliTieteellinenvertaisarvioitu

3 Sitaatiot (Scopus)
2 Lataukset (Pure)

Abstrakti

Self-assembled prodrugs (SAPDs), which combine prodrug strategy and the merits of self-assembly, not only represent an appealing type of therapeutics, enabling the spontaneous organization of supramolecular nanocomposites with defined structures in aqueous environments, but also provide a new method to formulate existing drugs for more favorable outcomes. To increase drug loading and combination therapy, we covalently conjugated paclitaxel (PTX) and camptothecin (CPT) through a disulfide linker into a prodrug, designated PTX-S-S-CPT. The successful production of PTX-S-S-CPT prodrug was confirmed by nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). This prodrug spontaneously undergoes precipitation in aqueous surroundings. Taking advantage of a flow-focusing microfluidics platform, the prodrug nanoparticles (NPs) have good monodispersity, with good reproducibility and high yield. The as-prepared prodrug NPs were characterized with dynamic light scattering (DLS) and transmission electron microscopy (TEM), demonstrating spherical morphology of around 200 nm in size. In the end, the self-assembled NPs were added to mouse embryonic fibroblast (MEF), mouse lung adenocarcinoma and Lewis lung carcinoma (LLC) cell lines, and human non-small cell lung cancer cell line A549 to evaluate cell viability and toxicity. Due to the redox response with a disulfide bond, the PTX-S-S-CPT prodrug NPs significantly inhibited cancer cell growth, but had no obvious toxicity to healthy cells. This prodrug strategy is promising for co-delivery of PTX and CPT for lung cancer treatment, with reduced side effects on healthy cells.

AlkuperäiskieliEnglanti
Artikkeli1169
JulkaisuPharmaceutics
Vuosikerta12
Numero12
DOI - pysyväislinkit
TilaJulkaistu - joulukuuta 2020
OKM-julkaisutyyppiA1 Julkaistu artikkeli, soviteltu

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