Paclitaxel–Paclitaxel Prodrug Nanoassembly as a Versatile Nanoplatform for Combinational Cancer Therapy

Abstract

Recently, nanomedicine without drug carriers has attracted many pharmacists' attention. A novel paclitaxel-s-s-paclitaxel (PTX-s-s-PTX) conjugate with high drug loading (∼78%, w/w) was synthesized by conjugating paclitaxel to paclitaxel by using disulfide linkage. The conjugate could self-assemble into uniform nanoparticles (NPs) with 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR) encapsulated within the core of PTX-s-s-PTX NPs for photothermal therapy (PTT). The DiR-loaded self-assembled nanoparticles (DSNs) had a mean diameter of about 150 nm and high stability in biological condition. A disulfide bond is utilized as a redox-responsive linkage to facilitate a rapid release of paclitaxel in tumor cells. DSNs indicated significant cytotoxicity as a result of the synergetic chemo-thermal therapy. DSNs were featured with excellent advantages, including high drug loading, redox-responsive releasing behavior of paclitaxel, capability of loading with photothermal agents, and combinational therapy with PTT. In such a potent nanosystem, prodrug and photothermal strategy are integrated into one system to facilitate the therapy efficiency.

iRGD‐paclitaxel conjugate nanoparticles for targeted paclitaxel delivery

“…The zeta potential of iRGD‐PTX NPs in deionized water is −19.4 mV. The negative surface charges arise from PTX (Han et al, ). The zeta potential of iRGD‐PTX NPs in PBS buffer (−20.8 mV), 5% FBS containing PBS buffer (−17.3 mV), and 10% FBS containing PBS buffer (−17.6 mV) are similar to that in deionized water.…”

“…Abraxane significantly increases the compliance of patients (Yardley, ) However, Abraxane may also cause neurotoxicity (Sahoo & Kumar, ). In order to obtain better clinical use of PTX, many PTX delivery systems have been developed and investigated, including micelles (Han et al, ; Luo, Han, Xu, Chen, & Zhang, ), nanoparticles (Jiang et al, ; Wang et al, ; Xiang et al, ; Xin et al, ), liposomes (Hong et al, ; Monteiro et al, ; Wang et al, ), PTX prodrugs (Han et al, ; Jiang et al, ; Jiang et al, ; Luo et al, ; Tam, Gao, & Kwon, ), and so on. Among these PTX delivery systems, PTX prodrugs, especially targeting peptide‐PTX conjugates (Bianchi et al, ; Colombo et al, ; Dal Corso et al, ; Zanella et al, ), achieved great attention because conjugating targeting peptide onto PTX can not only increase the water solubility of PTX, but also endow the conjugate with the capability of targeting tumor cells by ligand–receptor interactions.…”

Engineering small molecule nanodrugs to overcome barriers for cancer therapy

“…A common way to construct drug-drug dimers is combining them through a cleavable disulfide linker. Up to now, several drug-drug dimers including paclitaxel dimers, [64][65][66] doxorubicin dimers, 67 and CPT dimers 68 have been prepared by this way. The reason to use disulfide bond is that not only it is susceptible to the reductive environment, but also it can balance the competition between intermolecular forces involved in the self-assembly of nanomedicines.…”

Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity

“…Designing redox-responsive drug carriers has garnered interest over the past years. A disulfide bond (-S-S-) is used as a redox-responsive linker, which is relatively stable in plasma and can be cleaved in a reductive environment; thereby enabling rapid release of the loaded drug [26,27].…”