Tumor targeting effects of a novel modified paclitaxel-loaded discoidal mimic high density lipoproteins

Abstract

Objective: Monocholesterylsuccinate (CHS)-modified paclitaxel-loaded discoidal reconstituted high density lipoproteins (cP-d-rHDL) as novel biomimetic nanocarriers that were developed for tumor targeting delivery to avoid unexpected drug leakage from discoidal reconstituted high density lipoproteins (d-rHDL) during remodeling process associated with lecithin-cholesterol acyltransferase (LCAT). Methods: Their in vitro characterizations and biomimetic properties, simultaneously tumor distribution and pharmacodynamics in tumor bearing mice were elaborately investigated. Results: In vitro characterization results showed that cP-d-rHDL had nano-size diameter, high negative zeta potential and high entrapment efficiency (EE). Furthermore, morphology study indicated that cP-d-rHDL did not remodel in the presence of LCAT, compared with that of paclitaxel-loaded d-rHDL (P-d-rHDL, not modified). And cellular uptake, together with cytotoxicity toward tumor cells of cP-d-rHDL was not affected after interaction with LCAT. Tumor distribution and pharmacodynamics tests revealed that cP-d-rHDL possessed specific targeting property and anti-tumor efficacy. Conclusion: cP-d-rHDL served to restrain remodeling process and drug leakage, at the same time reinforce the targeting effect, and could act as a potential drug delivery system for cancer therapy.

Synthetic High-Density Lipoprotein-Like Nanoparticles as Cancer Therapy

“…This biological maturation of discoidal HDLs can lead to unwanted leakage of drug cargo [69]. To combat this problem, researchers used monocholesterylsuccinate (CHS) instead of cholesterol to prevent particle interaction with LCAT, and anchored apoA-I on the particle by covalently linking it to CHS [76, 86]. The authors employed a CHS-modified discoidal HDL-like NPs, termed recombinant HDL (rHDL), and loaded it with paclitaxel, a mitotic inhibitor used to treat a variety of cancers.…”

Targeted delivery of doxorubicin and vincristine to lymph cancer: evaluation of novel nanostructured lipid carriers in vitro and in vivo

“…It has been reported that the nanoparticles with the size less than 200 nm can significantly accumulate in tumor by ''filtration'' mechanism (Xu et al, 2009;Duan et al, 2015). Small particles are also minimal endocytosis by macrophages, so destruction and clearance could be minimized, and the nanocarriers were desirable for in vitro and in vivo drug delivery (Accardo et al, 2012;Wang et al, 2013). The zeta potentials of DOX/VCR NLCs were +21 mV.…”

Theranostic Nanoemulsions: Codelivery of Hydrophobic Drug and Hydrophilic Imaging Probe for Cancer Therapy and Imaging

“…We also needed to verify that the TNE could be engulfed by cells [34][35][36]. The fluorescence microscope was used to visualize the internalization and distribution of SRB-VE in KB-3-1 and KB-8-5 cells ( Figure 4A).…”