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pH-triggered echogenicity and contents release from liposomes.

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%).

journal_name

Mol Pharm

journal_title

Molecular pharmaceutics

authors

Nahire R,Hossain R,Patel R,Paul S,Meghnani V,Ambre AH,Gange KN,Katti KS,Leclerc E,Srivastava DK,Sarkar K,Mallik S

doi

10.1021/mp500186a

subject

Has Abstract

pub_date

2014-11-03 00:00:00

pages

4059-68

issue

11

eissn

1543-8384

issn

1543-8392

journal_volume

11

pub_type

杂志文章

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