Self‐Assembly of Porphyrin–Paclitaxel Conjugates Into Nanomedicines: Enhanced Cytotoxicity due to Endosomal Escape

Abstract

Nanomedicines assembled directly from drug molecules possess several advantages, including precise molecular structure and high content of drugs. Herein, porphyrin-paclitaxel conjugates (Py-s-s-PTX) were synthesized by using a disulfide bond as a linker. The Py-s-s-PTX could self-assemble into nanoparticles (Py-s-s-PTX NPs) with a size of about 100 nm via disulfide-induced assembly. Py-s-s-PTX NPs are highly stable under biological conditions and could be destroyed in the presence of reducing agents as revealed by dynamic light scattering. The obtained Py-s-s-PTX NPs could be internalized by cancer cells via endocytosis and disassociated in the reducing cytoplasm, thus releasing PTX in cancer cells. Endosomal escape triggered upon irradiation could enhance the cytotoxicity of paclitaxel, and Py-s-s-PTX NPs possess cytotoxicity comparable to that of free PTX. We believe that this disulfide-assembled nanomedicine represents a new and important development for chemotherapy in cancer therapy.

Conjugation of Aspergillus flavipes Taxol with Porphyrin Increases the Anticancer Activity of Taxol and Ameliorates Its Cytotoxic Effects

“…The chemical conjugation of Taxol with porphyrin was conducted according to [17,29,43], as illustrated in Figure 4A. Briefly, tetracarboxyphenyl porphyrin (0.3 mM), N,N -dicyclohexylcarbodi imide (DCC) (0.25 mM), 4-dimethylaminopyridine (DMAP) (0.1 mM), and Taxol (0.2 mM) were dissolved in tetrahydrofuran (THF) (10 mL), and the mixture was then stirred in the dark at room temperature under nitrogen conditions for 72 h. The solution was filtered, and the filtrate was dried under the reduced pressure to remove the solvent.…”

“…With the global commercial and clinical values of Taxol, the side effect and required high doses are still the major challenges to this drug, especially in developing countries. Conjugation with various biocompatible polymers is a reliable approach to increase the efficiency of this drug and to reduce its side effects [17]. Porphyrin has been developed as a smart material for drug delivery, which can potentially decrease the side effects of the target drug, increasing its efficient activities.…”

Engineering small molecule nanodrugs to overcome barriers for cancer therapy

“…Apart from the proton sponge effect, external stimuli, such as light, could also disrupt endosome to induce the enhanced cytotoxicity of anticancer drugs. For example, Xie et al 130 reported that small molecule nanodrugs self-assembled from porphyrin-paclitaxel conjugates could escape from endosome triggered by light irradiation. Under light irradiation, release of 1 O 2 damaged the endosome and then the released porphyrin-paclitaxel conjugates induced enhanced cancer therapy.…”

PEGylation of Ginsenoside Rg3-Entrapped Bovine Serum Albumin Nanoparticles: Preparation, Characterization, and In Vitro Biological Studies

“…Haemolysis was determined from three independent experiments. The haemolytic ratio (HR) was calculated according to the following equation: Cellular uptake and distribution of Rg3 from the NPs were observed by CLSM (Leica, Germany) [32]. First, mPEG-Rg3-BSA NPs (180 μM) were labelled with FITC to investigate the uptake of NPs into L929 and HepG2 cells according to the method of Leamon and Low (1991).…”