Expansile Nanoparticles: Synthesis, Characterization, and in Vivo Efficacy of an Acid-Responsive Polymeric Drug Delivery System

Abstract

Nanoparticles are finding increased uses in drug delivery applications as a means to increase treatment efficacy and improve patient care. Here, we report engineered polymeric nanoparticles that undergo a hydrophobic to hydrophilic transition at pH 5 to afford swelling and rapid release of their contents. As our clinical interest lies in the prevention of lung tumor recurrence following resection, the nanoparticles were evaluated in a model mimicking microscopic disease, akin to residual occult tumor that can remain at the resection margin following surgery. Expansile nanoparticles loaded with paclitaxel, a poorly water-soluble anticancer drug, prevent establishment of lung cancer in vivo and are superior to the conventional drug delivery method for paclitaxel using Cremophor EL/ethanol.

Amplification of oxidative stress by a dual stimuli-responsive hybrid drug enhances cancer cell death

“…A hybrid anticancer drug QCA was designed to be activated by acidic pH and high level of H 2 O 2 (ref. 27). QCA as a dual stimuli-responsive hybrid anticancer agent was synthesized as shown in Supplementary Fig.…”

“…We developed QCA that exerts dual and synergistic therapeutic actions in cancer environments associated with a high concentration of H 2 O 2 and acidic pH 8,27 . As shown in Fig.…”

Light-Sensitive Polymeric Nanoparticles Based on Photo-Cleavable Chromophores

“…Investigated approaches include the embedding of small-molecule compounds into collapsed gels and their swelling-induced release upon the appliance of an external trigger. 108,109 A detailed description of different stimuli-responsive microgels is discussed in a following section.…”

“…Nevertheless, these materials cannot be assigned to the field of microgels. An alternative mechanism for the delivery of hydrophobic compounds from hydrophilic microgels was recently demonstrated by Griset et al 109 The described concept is based on the generation of swollen hydrogel nanoparticles from hydrophobic polymer latexes as a result of a stimulus-induced transition of the hydrophilicity of the network-forming polymer from hydrophobic to hydrophilic. To this extend, crosslinked particles consisting of a hydrophobic polymer containing acetal protected diol groups in the backbone were prepared by inverse miniemulsion polymerization.…”

“…This concept was recently described by Griset et al for the delivery of paclitaxel from pH-sensitive expansible nanoparticles based on acetal protected polymers. 109 On the other hand, the covalent attachment of a drug to a hydrophilic polymeric carrier system is highly efficient to prevent its leakage. A triggered release can be achieved by the utilization of a specific linker molecule between drug and polymer which is cleavable upon the appliance of a certain trigger.…”