Recent advances in stimuli-responsive degradable block copolymer micelles: synthesis and controlled drug delivery applications

Abstract

(Bio)degradation in response to external stimuli (stimuli-responsive degradation, SRD) is a desired property in constructing novel nanostructured materials. For polymer-based multifunctional drug delivery applications, the degradation enables fast and controlled release of encapsulated therapeutic drugs from delivery vehicles in targeted cells. It also ensures the clearance of the empty device after drugs are delivered to the body. This review summarizes recent development of various strategies to the design and synthesis of self-assembled micellar aggregates based on novel amphiphilic block copolymers having different numbers of stimuli-responsive cleavable elements at various locations. These cleavable linkages including disulfide, acid-labile, and photo-cleavable linkages are incorporated into micelles, and then are cleaved in response to cellular triggers such as reductive reaction, light, and low acid. The well-designed SRD micelles have been explored as controlled/enhanced delivery vehicles of drugs and genes. For future design and development of effective stimuli-responsive degradable micelles toward tumor-targeting delivery applications in vivo, a high degree of control over degradation for tunable release of encapsulated anticancer drugs as well as bioconjugation for active tumor-targeting is required.

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

“…Tunable release has been a major component of the recent boom in nanomedicine research, as stimuli-responsive carriers are optimized to release payload only upon certain cues either intracellularly or within the microenvironment of tumors and can potentially lower systemic toxicity of chemotherapeutic agents [19][20][21]. Commonly utilized triggers for payload release include a slightly acidic pH in the microenvironment, overexpression of specific enzymes, localized hyperthermia, and increased levels of glutathione within the cell [22][23][24][25][26][27]. Moreover, heightened control over release has grand implications on rational combinatorial therapies since co-delivery does not always imply simultaneous release, and ordered release of multiple therapeutic agents may achieve maximally synergistic effects [28][29][30].…”

Advances in drug delivery systems based on synthetic poly(hydroxybutyrate) (co)polymers

“…The recent interest in stimuli-responsive polymers [162][163][164] and the unique properties of micelles containing a PHB core promoted the development of PHB-based stimuliresponsive drug carriers [57,165,166]. Indeed, thermo-or pH-responsive copolymers enable to tune the physico-chemical properties of the micelles and also to modify the drug release profile [167][168][169][170][171].…”

MRI‐Visual Order–Disorder Micellar Nanostructures for Smart Cancer Theranostics

“…[14] Moreover, the stimuli responsive order-disorder transition-enabled block copolymer, PS-b-PAA, had dual advantages from both the synthetic and application aspects. [15] The stimuli-responsive order-disorder core-shell nanoassembly was used to solubilise the DOx in the hydrophobic core of the styrene and hence, reduce the possibility of unintended exposure and the consequent cytotoxicity for normal cells.…”