Sequential release of nanoparticle payloads from ultrasonically burstable capsules

Abstract

In many biomedical contexts ranging from chemotherapy to tissue engineering, it is beneficial to sequentially present bioactive payloads. Explicit control over the timing and dose of these presentations is highly desirable. Here, we present a capsule-based delivery system capable of rapidly releasing multiple payloads in response to ultrasonic signals. In vitro, these alginate capsules exhibited excellent payload retention for up to 1 week when unstimulated and delivered their entire payloads when ultrasonically stimulated for 10 to 100 s. Shorter exposures (10 s) were required to trigger delivery from capsules embedded in hydrogels placed in a tissue model and did not result in tissue heating or death of encapsulated cells. Different types of capsules were tuned to rupture in response to different ultrasonic stimuli, thus permitting the sequential, on-demand delivery of nanoparticle payloads. As a proof of concept, gold nanoparticles were decorated with bone morphogenetic protein-2 to demonstrate the potential bioactivity of nanoparticle payloads. These nanoparticles were not cytotoxic and induced an osteogenic response in mouse mesenchymal stem cells. This system may enable researchers and physicians to remotely regulate the timing, dose, and sequence of drug delivery on-demand, with a wide range of clinical applications ranging from tissue engineering to cancer treatment.

Preparation of a mesoporous silica-based nano-vehicle for dual DOX/CPT pH-triggered delivery

“…By contrast, CPT@MSN-hyd-PEG-hyd-DOX under the same conditions exhibit a sustained CPT release for more than 10 h, which might be ascribed to the physical absorption of the drug inside the nanochannels (Luo et al., 2013 ). The smooth release pattern observed for CPT can be especially beneficial for combination therapy (Cao et al., 2014 ; Xu et al., 2015b ; Kennedy et al., 2016 ).…”

A Step‐by‐Step Multiple Stimuli‐Responsive Nanoplatform for Enhancing Combined Chemo‐Photodynamic Therapy

“…[14,15] To address premature drug release, one effective strategy is to chemically conjugate the drug to the polymer backbone to form polymeric prodrugs. [25] The release behavior in spatial-, temporal-, and dosage-controlled fashion becomes possible in tumors when triggered by exogenous [26][27][28][29][30] and endogenous [31][32][33][34][35][36] stimuli. [20,21] In addition, a new strategy in development is to encapsulate a photosensitizer (PS) into nanoparticles to improve cellular uptake of the nanoparticles with a short-time light irradiation, which is known as "photochemical internalization" (PCI), since PS can energize surrounding molecular oxygen ( 3 O 2 ) to generate reactive oxygen species (ROS) that can induce lipid peroxidation, further leading to an increase of cell membrane permeability.…”

In vitro and in vivo assessment of controlled release and degradation of acoustically responsive scaffolds

“…Acoustically-responsive scaffolds (ARSs), comprising fibrin scaffolds doped with sonosensitive emulsion, are highly tunable since emulsion (e.g., structure, size), scaffold (e.g., density, geometry), and US properties (e.g., frequency, amplitude) can be easily modified [34]. Compared to approaches using unfocused, low-frequency (i.e., 20 kHz) US [35, 36], the use of focused, high frequency (i.e., > 1 MHz) US to trigger ADV and payload release from an ARS could enable higher spatial resolution, even within deeply-located implants.…”