pH-temperature dual-sensitive nucleolipid-containing stealth liposomes anchored with PEGylated AuNPs for triggering delivery of doxorubicin

• Published in: International journal of pharmaceutics Vol. 619; p. 121691
• Main Authors: García, Mónica C., Calderón-Montaño, José Manuel, Rueda, Manuela, Longhi, Marcela, Rabasco, Antonio M., López-Lázaro, Miguel, Prieto-Dapena, Francisco, González-Rodríguez, María Luisa
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10.05.2022
• Subjects: Anticancer activity; Antineoplastic Agents - therapeutic use; Cell Line, Tumor; Cholesterol - chemistry; Cytidine Diphosphate - therapeutic use; Doxorubicin; Drug delivery; Gold - therapeutic use; Gold nanoparticles; Humans; Hydrogen-Ion Concentration; Hyperthermia, Induced; Langmuir monolayers; Liposomes - chemistry; Metal Nanoparticles; Neoplasms - drug therapy; pH-responsive liposomes; Polyethylene Glycols - chemistry; Temperature; Thermo-responsive liposomes; pH-responsive liposomes; Drug delivery; Langmuir monolayers; Thermo-responsive liposomes; Gold nanoparticles; Anticancer activity
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2022.121691

[Display omitted] •The nucleolipid DG-CDP, DPPC and cholesterol were used for preparing liposomes (Lip).•Doxorubicin (Dox) was loaded and PEGylated AuNPs were anchored onto Liṕs surfaces.•Nanometric size, high Dox loading and controlled drug release were achieved.•Triggering delivery of Dox was observed at acidic pH and hyperthermia temperature.•Liposomal formulations displayed efficacy against breast and ovarian cancer cells. Liposomes (Lip) are useful nanocarriers for drug delivery and cancer nanomedicine because of their ability to efficiently encapsulate drugs with different physical and chemical properties. The pH gradient between normal and tumoral tissues, and their rapid metabolism that induces hyperthermia encourage the development of pH- and thermo-sensitive Lip for delivering anticancer drugs. Nucleolipids have been studied as scaffolding material to prepare Lip, mainly for cancer therapy. Herein, we report for the first time the use of 1,2-dipalmitoyl-sn-glycero-3-(cytidine diphosphate) (DG-CDP) to develop pH/thermo-sensitive nucleolipid-containing stealth Lip stabilized by combination with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol, anchored with NH2-PEGylated gold nanoparticles (PEG-AuNPs, 15 nm) for triggering delivery of doxorubicin (Dox). The optimal composition of DPPC, DG-CDP and cholesterol (94:3:3) was established by Langmuir isotherms. Unloaded and Dox-loaded Lip and AuNPs-Lip exhibited nano-scale sizes (415–650 nm), acceptable polydispersity indexes (<0.33), spherical shapes, and negative Z-potential (−23 to −6.6 mV) due to the phosphate groups of DG-CDP, which allowed the anchoring with positively charged AuNPs. High EE% were achieved (>78%) and although efficient control in the Dox release towards different receptor media was observed, the release of Dox from PEG-AuNPs-Lip-Dox was significantly triggered at acidic pH and hyperthermia conditions, demonstrating its responsiveness to both stimuli. Dox-loaded Lip showed high cytotoxic activity against MDA-MB-231 breast cancer cells and SK-OV-3 ovarian cancer cells, suggesting that Dox was released from these nanocarriers over time. Overall, the liposomal formulations showed promising properties as stimuli-responsive nanocarriers for cancer nanomedicine, with prospects for hyperthermia therapy.