A new class of nanoparticles, synthesized by a research team at the University of California, Davis, to prevent premature
drug release, holds promise for greater accuracy and effectiveness in delivering cancer drugs to tumors. Kit Lam, professor
and chair of the Department of Biochemistry and Molecular Medicine and his team reported on the synthesis of a novel class
of micelles called dual-responsive boronate cross-linked micelles (BCMs) , which produce physicochemical changes in response
to specific triggers.
The researchers reported that micelles reversibly cross-linked by boronate esters show in vitro and in vivo stability and thus minimize premature drug release under physiological conditions. After reaching the tumor sites, drug release
is activated by cleavage of the boronate esters by the acidic conditions around the tumor or in the target cells or by the
administration of mannitol (1). A micelle is an aggregate of surfactant molecules dispersed in water-based liquid such as
saline. They are nanosized, about 25–50 nm , and can function as nanocarriers for drug delivery. "This use of reversibly
cross-linked targeting micellar nanocarriers to deliver anticancer drugs helps prevent premature drug release during circulation
and ensures delivery of high concentrations of drugs to the tumor site," said Yuanpei Li, a postdoctoral fellow in Lam's laboratory
who created the novel nanoparticle with Lam, in a Jan. 18, 2012, University of California at Davis press release. "It holds
great promise for a significant improvement in cancer therapy."
Stimuli-responsive nanoparticles are gaining attention in the field of drug delivery due to their ability to transform in
response to specific triggers, notes the university release. Among these nanoparticles, stimuli-responsive cross-linked micelles
(SCMs) can serve as a nanocarrier system for tumor-targeting drug delivery.
SCMs and other nanoparticle systems seek to address the problem of premature drug release, which results in a drug not delivering
its payload to a given target. SCMs can better retain the encapsulated drug and minimize its premature release while circulating
in the blood pool. The introduction of environmentally sensitive cross-linkers makes these micelles responsive to the local
environment of the tumor. In these instances, the payload drug is released primarily in the cancerous tissue, according to
The dual-responsive boronate cross-linked micelles that Lam's team has developed are a second generation of SCMs able to respond
to multiple stimuli as tools for accomplishing the multistage delivery of drugs to a complex in
vivo tumor micro-environment, according to the university release. These BCMs deliver drugs based on the self-assembly of boronic
acid-containing polymers and catechol-containing polymers, both of which make these micelles unusually sensitive to changes
in the pH of the environment. The research team has optimized the stability of the resulting boronate cross-linked micelles
as well as their stimuli-response to acidic pH and mannitol.
This nanocarrier platform shows promise for drug delivery that minimizes premature drug release and can release the drug
on demand within the acidic tumor micro-environment or in the acidic cellular compartments when taken in by the target tumor
cells. It also can be induced to release the drug through the intravenous administration of mannitol.
1. K. Lam et al., "Well Defined, Reversible Boronate Crosslinked Nanocarriers for Targeted Drug Delivery in Response to Acidic
pH Values and cis-Diols," Angew. Chem., Int. Ed. Engl. online, DOI:10.1002/anie.201107144, Jan. 17, 2012.