Utilizing Stimuli Responsive Linkages to Engineer and Enhance Polymer Nanoparticle-Based Drug Delivery Platforms

Abstract

The devastating nature of cancer continues to be one of the leading causes of death in the world. Chemotherapy is among the most common forms of cancer treatment but comes with a host of adverse effects caused by the therapeutic agents damaging healthy tissue and organs. To limit these side effects, scientists have been designing stimuli responsive drug delivery vessels for targeted release. This Review focuses on the incorporation of stimuli responsive linkages in targeted drug delivery systems to enhance therapeutic efficiency. These platforms are primarily employed to control the distribution of anticancer agents in the body to reduce the adverse side effects caused by their toxicities. We will outline how drug delivery vessels are constructed so that exposure to select environmental and external stimuli releases the enclosed drug only at the target site. Stimuli responsive components are integrated within drug delivery vessels in the form of cross-linkers, polymers, and surface modifications. The changes, these moieties undergo upon stimuli exposure, cascade into larger scale alterations to the platforms, resulting in complete disassembly, reversible morphological variations, and enhanced cellular uptake. The ability for these modes of delivery to be initiated exclusively under stimuli exposure allows for release of toxic therapeutic agents to be confined only to the affected area.

Advances in Nanomaterials Used in Co-Delivery of siRNA and Small Molecule Drugs for Cancer Treatment

“…An emerging set of polymer-based drug delivery systems are being designed with moieties that are sensitive to changes in pH, temperature, the presence of glutathione, reactive oxygen species, and enzymes [54]. In the absence of disease, the bodily pH level is homeostatically maintained within a range of 7.35-7.45 [55].…”

Single and Multiple Stimuli-Responsive Polymer Particles for Controlled Drug Delivery

“…Multiple stimuli polymers have emerged as the new trend to achieve finer control of the release of drugs and avoid side effects [5][6][7][8]. While there are reviews focusing on the use of stimuli-responsive polymers for targeting or imaging purposes [9][10][11][12][13], this review will specifically summarize the progress in stimuli-responsive polymers as particles for controlled drug release, with a focus on the recent advances in the field. As there are already several recent reviews discussing the role of hydrogels in drug delivery [14][15][16][17][18][19], including the use of nanogels as particles for drug delivery, we will not include hydrogel polymer particles in this discussion.…”

Galactosed and Reduction-Responsive Nanoparticles Assembled from Trimethylchitosan–Camptothecin Conjugates for Enhanced Hepatocellular Carcinoma Therapy

“…The triggered release of bioactive drugs in target cells or tissues from prodrugs can reduce high systemic toxicity. This strategy can be achieved via linkers in response to various endogenous stimuli such as low pH, high glutathione (GSH) concentrations, and specific enzymes, as well as exogenous stimuli, such as heat and light [ 3 , 18 ]. In particular, disulfide linkages have been widely exploited for tumor drug delivery because of a specific degradation in response to elevated GSH concentration in tumor cells through a thiol–disulfide exchange reaction [ 19 ].…”