Multistage Continuous Targeting with Quantitatively Controlled Peptides on Chitosan-Lipid Nanoparticles with Multicore-Shell Nanoarchitecture for Enhanced Orally Administrated Anticancer In Vitro and In Vivo.
A DOX-loaded polysaccharide-lecithin reverse micelles triglyceride-based oral delivery nanocarrier (D-PL/TG NPs) conjugated with (i) RGD peptide for targeting to β1 integrin of M cells and (ii) Lyp-1 peptide for targeting to the p32 receptor of MDA-MB-231 cells is used to investigate the multistage continuous targeting capabilities of these peptide-conjugated nanocarriers (GLD-PL/TG NPs) for tumor therapy. Variations in the targeting efficacy and pharmacokinetic properties are investigated by quantitatively controlling the surface density of different peptides on the nanoparticles. In vitro permeability in a human follicle-associated epithelium model and cytotoxicity against MDA-MB-231 cells indicate that the nanocarriers conjugated with high RGD peptide concentrations display a higher permeability due to the existence of M cells with higher transcytosis activity, but a higher concentration of conjugated Lyp-1 peptide exhibits the lowest cell viability. Being benefited from specific targeting of peptide conjugation, improved bioavailability and enhanced tumor accumulation are achieved by the GLD-PL/TG NPs, leading to better antitumor efficacy. The results of in vivo biodistribution and antitumor studies reveal that the effect of LyP-1 peptide is more predominant than that of RGD peptide. This proof of multistage continuous targeting may open the door to a new generation of oral drug delivery systems in targeted cancer therapy.
['Su|Chia-Wei|CW|', 'Yen|Ching-Shu|CS|', 'Chiang|Chih-Sheng|CS|', 'Hsu|Chin-Hao|CH|', 'Chen|San-Yuan|SY|']
D000284:Administration, Oral D000818:Animals D000970:Antineoplastic Agents D018938:Caco-2 Cells D016923:Cell Death D002463:Cell Membrane Permeability D048271:Chitosan D004317:Doxorubicin D004337:Drug Carriers D004705:Endocytosis D020895:Enterocytes D005260:Female D006801:Humans D008024:Ligands D008055:Lipids D008807:Mice, Inbred BALB C D008856:Microscopy, Fluorescence D053758:Nanoparticles D010455:Peptides D055672:Static Electricity D014018:Tissue Distribution
Oral Administration RGD Lyp-1 Drug targeting Multistage continuous targeting delivery