Triple-negative breast cancers (TNBCs), devoid of hormone receptors and human epidermal growth-factor receptor-2/Neu expression, bring about poor prognosis and induce a high rate of systematic metastases. The ineffectiveness of current therapies on TNBCs could be attributed to the lack of efficient targeted therapy. Paclitaxel (PTX) is considered one of first-line chemotherapeutics for TNBC treatment but, due to its low aqueous solubility and nonspecific accumulation, results in poor antitumor efficacy. The present study is aimed at enhancing the chemotherapeutic potency of PTX by improving the stability and targeting efficiency of PTX-loaded nanoparticulate drug carriers. Here, PTX was incorporated in nontoxic and endogenous material, human serum albumin (HSA), via an innovative disulfide reduction method to construct HSA-based PTX nanoparticle (HSA-PTX NP) to not only realize redox-responsive drug release but also improve in vivo stability. Besides, W peptide was selected as a target ligand to be conjugated with HSA-PTX NP for endowing active targeting ability. The resulting Wpep-HSA-PTX NP possessed a spherical structure (118 nm), 9.87% drug-loading content, and 86.3% entrapment efficiency. An in vitro drug release test showed that PTX release from Wpep-HSA-PTX NP was of a redox-responsive manner. Furthermore, cellular uptake of Wpep-HSA-PTX NP was significantly enhanced, exhibiting the improved antiproliferation and antitube formation effects of PTX in vitro. In comparison with those commercial formulations and conventional HSA NP, Wpep-HSA-PTX NP exhibited better pharmacokinetic behaviors and tumor homing characteristics. The antitumor efficacy of Wpep-HSA-PTX NP was further confirmed by the strong pro-apoptotic effect and reduced tumor burden. In a word, this evidence highlighted the proof of concept for Wpep-HSA NP as a promising conqueror to the ineffectiveness of TNBC therapy.
Keywords: W peptide; disulfide reduction; drug delivery; human serum albumin; triple-negative breast cancer.