Dual-ligand modified liposomes provide effective local targeted delivery of lung-cancer drug by antibody and tumor lineage-homing cell-penetrating peptide

Abstract

The abilities of a drug delivery system to target and penetrate tumor masses are key factors in determining the system’s chemotherapeutic efficacy. Here, we explored the utility of an anti-carbonic anhydrase IX (anti-CA IX) antibody and CPP33 dual-ligand modified triptolide-loaded liposomes (dl-TPL-lip) to simultaneously enhance the tumor-specific targeting and increase tumor cell penetration of TPL. In vitro, the dl-TPL-lip increased the cytotoxicity of TPL in CA IX-positive lung cancer cells, which showed tunable size (137.6 ± 0.8 nm), high-encapsulation efficiency (86.3 ± 2.6%) and sustained release. Dl-TPL-lip significantly improved the ability of liposomes to penetrate 3 D tumor spheroids and exhibited a superior inhibiting effect. Furthermore, pharmacokinetic studies in rats that received TPL liposomal formulations by endotracheal administration showed a reduced concentration of TPL (17.3%–30.6% compared to free TPL) in systemic circulation. After pulmonary administration in orthotopic lung tumor-bearing mice, dl-TPL-lip significantly enhanced TPL anti-cancer efficacy without apparent systemic toxicity. This dual-ligand modified liposomal vehicle presents a potential system for localized and targeted delivery of anti-cancer drugs to improve their efficacy.

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

“…Triptolide loaded onto a peptide fragment (TPS-PF-A 299-585 ) is specifically targeted to the kidney and with less toxicity [449]. Some modified triptolide-loaded liposomes are reported to contribute a targeted delivery with lower toxicity and better efficacy in lung cancer treatment [450]. Similarly, triptolide-loaded exosomes enhances apoptosis in human ovarian cancer SKOV3 cells [451].…”

Cancer cell membrane coated silica nanoparticles loaded with ICG for tumour specific photothermal therapy of osteosarcoma

“…To address this issue, the integration of corresponding targeting ligands into the DDS has been adopted [15,16]. In the past decades, targeting ligands varying from small molecules to monoclonal antibodies have been successfully integrated into DDS to improve its tumour targeting capabilities [17][18][19]. However, some unexpected side effects, such as immunoreaction as well as cytotoxicity are raised due to the ectogenic nature of these ligands and the complicated synthetic process which might contain by-products.…”

Synergistic combination therapy of lung cancer using paclitaxel- and triptolide-coloaded lipid–polymer hybrid nanoparticles

“… 20 , 21 However, TL has a poor solubility in water (0.017 mg/mL). 22 Significant and rapid fluctuations of TL in plasma by oral administration (T max from 10.0 to 19.5 minutes; t 1/2 from 16.8 to 50.6 minutes) likely contribute to its toxicity, which is characterized by injury to hepatic, renal, digestive, reproductive, and hematological systems. 23 Therefore, it is necessary to design LPNs for prolonging drug release and improving its safety.…”