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pH-triggered echogenicity and contents release from liposomes
Journal article   Open access   Peer reviewed

pH-triggered echogenicity and contents release from liposomes

Rahul Nahire, Rayat Hossain, Rupa Patel, Shirshendu Paul, Varsha Meghnani, Avinash H Ambre, Kara N Gange, Kalpana S Katti, Estelle Leclerc, D K Srivastava, …
Molecular pharmaceutics, Vol.11(11), pp.4059-4068
11/03/2014
DOI: 10.1021/mp500186a
PMCID: PMC4224524
PMID: 25271780
url
https://doi.org/10.1021/mp500186aView
Published (Version of record) Open Access

Abstract

Liposomes are representative lipid nanoparticles widely used for delivering anticancer drugs, DNA fragments, or siRNA to cancer cells. Upon targeting, various internal and external triggers have been used to increase the rate for contents release from the liposomes. Among the internal triggers, decreased pH within the cellular lysosomes has been successfully used to enhance the rate for releasing contents. However, imparting pH sensitivity to liposomes requires the synthesis of specialized lipids with structures that are substantially modified at a reduced pH. Herein, we report an alternative strategy to render liposomes pH sensitive by encapsulating a precursor which generates gas bubbles in situ in response to acidic pH. The disturbance created by the escaping gas bubbles leads to the rapid release of the encapsulated contents from the liposomes. Atomic force microscopic studies indicate that the liposomal structure is destroyed at a reduced pH. The gas bubbles also render the liposomes echogenic, allowing ultrasound imaging. To demonstrate the applicability of this strategy, we have successfully targeted doxorubicin-encapsulated liposomes to the pancreatic ductal carcinoma cells that overexpress the folate receptor on the surface. In response to the decreased pH in the lysosomes, the encapsulated anticancer drug is efficiently released. Contents released from these liposomes are further enhanced by the application of continuous wave ultrasound (1 MHz), resulting in substantially reduced viability for the pancreatic cancer cells (14%).
 Antineoplastic Agents - administration & dosage Antineoplastic Agents - pharmacology Carcinoma, Pancreatic Ductal - drug therapy Carcinoma, Pancreatic Ductal - metabolism Carcinoma, Pancreatic Ductal - pathology Cell Movement - drug effects Cell Proliferation - drug effects Doxorubicin - administration & dosage Doxorubicin - analogs & derivatives Doxorubicin - pharmacology Drug Delivery Systems Folate Receptor 1 - metabolism Humans Hydrogen-Ion Concentration Liposomes - administration & dosage Liposomes - chemistry Liposomes - metabolism Microscopy, Atomic Force Nanoparticles Pancreatic Neoplasms - drug therapy Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - pathology Polyethylene Glycols - administration & dosage Polyethylene Glycols - pharmacology Tumor Cells, Cultured Ultrasonics - methods

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