Natural Particulates Inspired Specific-Targeted Codelivery of siRNA and Paclitaxel for Collaborative Antitumor Therapy

Abstract

The effective combination of drugs promoting antiangiogenesis and apoptosis effects has proven to be a promising collaborative tumor antidote; and the codelivery of small interfering RNA (siRNA) and chemotherapy agents within one efficient vehicle has gained more attention over single regimen administration. Herein, vascular endothelial growth factor specific siRNA (siVEGF) and paclitaxel (PTX) were introduced as therapeutic companions and coencapsulated into naturally mimic high-density lipoproteins (rHDL/siVEGF-PTX), so that various mechanisms of treatment can occur simultaneously. The terminal nanoparticles share capacity of specific-targeting to tumor cells overexpressed scavenger receptor class B type I (SR-BI) and deliver siVEGF and PTX into cytoplasm by a nonendocytosis mechanism. By exchanging HDL core lipids with hydrophobic therapeutics, rHDL/siVEGF-PTX possessed particle size of ∼160 nm, surface potential of ∼-20 mV, and desirable long-term storage stability. In vitro results confirmed that the parallel activity of siVEGF and PTX displayed enhanced anticancer efficacy. The half-maximal inhibitory concentration (IC) of rHDL/siVEGF-PTX toward human breast cancer MCF-7 cell is 0.26 μg/mL (PTX concentration), which presents a 14.96-fold increase in cytotoxicity by taking Taxol as comparison. Moreover, in vivo results further demonstrated that rHDL/siVEGF-PTX performed enhanced tumor growth inhibition via natural targeting pathway, accompanied by remarkable inhibition of neovascularization in situ caused by siVEGF silencing in down-regulation of VEGF proteins. On the premise of effective drug codelivery, rHDL/siVEGF-PTX demonstrated high tumor targeting for collaborative antitumor efficacy without side effects after systemic administration, and this bioinspired strategy could open an avenue for exploration of combined anticancer therapy.

Progress in Natural Compounds/siRNA Co-delivery Employing Nanovehicles for Cancer Therapy

“…Using a combination of siRNA–VEGF and paclitaxel is also beneficial in anticancer therapy. The siRNA–VEGF suppresses metastasis of cancer cells, as well as angiogenesis and neovascularization of cancerous tissues, while paclitaxel exerts its inhibitory effect on the growth and viability of cancer cells …”

“…The siRNA−VEGF suppresses metastasis of cancer cells, as well as angiogenesis and neovascularization of cancerous tissues, while paclitaxel exerts its inhibitory effect on the growth and viability of cancer cells. 294 Stathmin 1 (STMN1) is an oncogene that promotes growth and differentiation of cancer cells. 295 Targeting STMN1 is important in anticancer therapy.…”

Peptide-Targeted High-Density Lipoprotein Nanoparticles for Combinatorial Treatment against Metastatic Breast Cancer

“…The tLyP-1-rHDL-PTX/GANT61 NPs were prepared via a thin-film hydration approach as detailed previously. ,, Briefly, SPC, cholesterol-tLyp, and cholesteryl ester (10:3:4 by weight) were dissolved with chloroform at an SPC concentration of 1 mg/mL and were combined with an ethanol solution containing PTX and GANT61 (SPC:PTX:GANT61 at 10:0.5:1.6 by weight) to prepare an oil phase. A thin film was then generated via the vacuum evaporation of the oil phase using a 37 °C water bath.…”

A TRAIL-Delivered Lipoprotein-Bioinspired Nanovector Engineering Stem Cell-Based Platform for Inhibition of Lung Metastasis of Melanoma

“…Solvent evaporation method was introduced to prepare lipid contents. rHDL/PEI-LA/pDNA was conducted by incubating the lipid contents with apoA I as described in previous studies with minor modifications 27. Briefly, 1 mg of soybean phospholipids (PC), 0.2 mg of cholesterol (C) and 0.1 mg of cholesteryl esters (CE) were dissolved in 5 mL of organic solvent (ethanol: dichloromethane = 5:2, V/V) and evaporated under vacuum at 37 °C until a thin film was formed.…”